Pulmonary Health Hub

Lingering postinfectious cough has been a concern across Canada this winter. Patients with this symptom (defined as a subacute cough, with symptoms lasting between 3 and 8 weeks after the infection) have many questions when they come to the clinic. But there is no evidence supporting pharmacologic treatment for postinfectious cough, according to an overview published on February 12 in the Canadian Medical Association Journal

“It’s something a lot of patients are worried about: That lingering cough after a common cold or flu,” lead author Kevin Liang, MD, of the Department of Family Medicine at The University of British Columbia in Vancouver, British Columbia, Canada, told this news organization. He added that some studies show that as much as a quarter of adult patients have this complaint.

Dr. Liang and his colleagues emphasized that the diagnosis of postinfectious cough is one of exclusion. It relies on the absence of concerning physical examination findings and other “subacute cough mimics” such as asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease, or use of angiotensin-converting enzyme inhibitors.

“Pertussis should be considered in patients with a paroxysmal cough, post-tussive vomiting, and inspiratory whoop,” they added. Coughs that persist beyond 8 weeks warrant further workup such as a pulmonary function test to rule out asthma or COPD. Coughs accompanied by hemoptysis, systemic symptoms, dysphagia, excessive dyspnea, or hoarseness also warrant further workup, they added. And patients with a history of smoking or recurrent pneumonia should be followed more closely.

In the absence of red flags, Dr. Liang and coauthors advised that there is no evidence supporting pharmacologic treatment, “which is associated with harms,” such as medication adverse effects, cost, strain on the medical supply chain, and the fact that pressurized metered-dose inhalers emit powerful greenhouse gases. “A lot of patients come in looking for solutions, but really, all the evidence says the over-the-counter cough syrup just doesn’t work. Or I see clinicians prescribing inhalers or different medication that can cost hundreds of dollars, and their efficacy, at least from the literature, shows that there’s really no improvement. Time and patience are the two keys to solving this,” Dr. Liang told this news organization.

Moreover, there is a distinct absence of guidelines on this topic. The College of Family Physicians of Canada’s recent literature review cited limited data supporting a trial of inhaled corticosteroids, a bronchodilator such as ipratropium-salbutamol, or an intranasal steroid if postnasal drip is suspected. However, “there’s a high risk of bias in the study they cite from using the short-acting bronchodilators, and what it ultimately says is that in most cases, this is self-resolving by around the 20-day mark,” said Dr. Liang. “Our advice is just to err on the side of caution and just provide that information piece to the patient.”
 

‘Significant Nuance’

Imran Satia, MD, assistant professor of respirology at McMaster University in Hamilton, Ontario, Canada, agreed that “most people who get a viral or bacterial upper or lower respiratory tract infection will get better with time, and there is very little evidence that giving steroids, antibiotics, or cough suppressants is better than waiting it out.” There is “significant nuance” in how to manage this situation, however.

“In some patients with underlying lung disease like asthma or COPD, increasing the frequency of regular inhaled steroids, bronchodilators, oral steroids, antibiotics, and chest imaging with breathing tests may be clinically warranted, and many physicians will do this,” he told this news organization. “In some patients with refractory chronic cough, there is no underlying identifiable disease, despite completing the necessary investigations. Or coughing persists despite trials of treatment for lung diseases, nasal diseases, and stomach reflux disease. This is commonly described as cough hypersensitivity syndrome, for which therapies targeting the neuronal pathways that control coughing are needed.”

Physicians should occasionally consider trying a temporary course of a short-acting bronchodilator inhaler, said Nicholas Vozoris, MD, assistant professor and clinician investigator in respirology at the University of Toronto, Toronto, Ontario, Canada. “I think that would be a reasonable first step in a case of really bad postinfectious cough,” he told this news organization. “But in general, drug treatments are not indicated.”
 

Environmental Concerns

Yet some things should raise clinicians’ suspicion of more complex issues.

“A pattern of recurrent colds or bronchitis with protracted coughing afterward raises strong suspicion for asthma, which can present as repeated, prolonged respiratory exacerbations,” he said. “Unless asthma is treated with appropriate inhaler therapy on a regular basis, it will unlikely come under control.”

Dr. Vozoris added that the environmental concerns over the use of metered dose inhalers (MDIs) are minimal compared with the other sources of pollution and the risks for undertreatment. “The authors are overplaying the environmental impact of MDI, in my opinion,” he said. “Physicians already have to deal with the challenging issue of suboptimal patient adherence to inhalers, and I fear that such comments may further drive that up. Furthermore, there is also an environmental footprint with not using inhalers, as patients can then experience suboptimally controlled lung disease as a result — and then present to the ER and get admitted to hospital for exacerbations of disease, where more resources and medications are used up.”

“In addition, in patients who are immunocompromised, protracted coughing after what was thought to be a cold may be associated with an “atypical” respiratory infection, such as tuberculosis, that will require special medical treatment,” Dr. Vozoris concluded.

No funding for the review of postinfectious cough was reported. Dr. Liang and Dr. Vozoris disclosed no competing interests. Dr. Satia reported receiving funding from the ERS Respire 3 Fellowship Award, BMA James Trust Award, North-West Lung Centre Charity (Manchester), NIHR CRF Manchester, Merck MSD, AstraZeneca, and GSK. Dr. Satia also has received consulting fees from Merck MSD, Genentech, and Respiplus; as well as speaker fees from AstraZeneca, GSK, Merck MSD, Sanofi-Regeneron. Satia has served on the following task force committees: Chronic Cough (ERS), Asthma Diagnosis and Management (ERS), NEUROCOUGH (ERS CRC), and the CTS Chronic Cough working group.

A version of this article appeared on Medscape.com.

Lingering postinfectious cough has been a concern across Canada this winter. Patients with this symptom (defined as a subacute cough, with symptoms lasting between 3 and 8 weeks after the infection) have many questions when they come to the clinic. But there is no evidence supporting pharmacologic treatment for postinfectious cough, according to an overview published on February 12 in the Canadian Medical Association Journal

“It’s something a lot of patients are worried about: That lingering cough after a common cold or flu,” lead author Kevin Liang, MD, of the Department of Family Medicine at The University of British Columbia in Vancouver, British Columbia, Canada, told this news organization. He added that some studies show that as much as a quarter of adult patients have this complaint.

Dr. Liang and his colleagues emphasized that the diagnosis of postinfectious cough is one of exclusion. It relies on the absence of concerning physical examination findings and other “subacute cough mimics” such as asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease, or use of angiotensin-converting enzyme inhibitors.

“Pertussis should be considered in patients with a paroxysmal cough, post-tussive vomiting, and inspiratory whoop,” they added. Coughs that persist beyond 8 weeks warrant further workup such as a pulmonary function test to rule out asthma or COPD. Coughs accompanied by hemoptysis, systemic symptoms, dysphagia, excessive dyspnea, or hoarseness also warrant further workup, they added. And patients with a history of smoking or recurrent pneumonia should be followed more closely.

In the absence of red flags, Dr. Liang and coauthors advised that there is no evidence supporting pharmacologic treatment, “which is associated with harms,” such as medication adverse effects, cost, strain on the medical supply chain, and the fact that pressurized metered-dose inhalers emit powerful greenhouse gases. “A lot of patients come in looking for solutions, but really, all the evidence says the over-the-counter cough syrup just doesn’t work. Or I see clinicians prescribing inhalers or different medication that can cost hundreds of dollars, and their efficacy, at least from the literature, shows that there’s really no improvement. Time and patience are the two keys to solving this,” Dr. Liang told this news organization.

Moreover, there is a distinct absence of guidelines on this topic. The College of Family Physicians of Canada’s recent literature review cited limited data supporting a trial of inhaled corticosteroids, a bronchodilator such as ipratropium-salbutamol, or an intranasal steroid if postnasal drip is suspected. However, “there’s a high risk of bias in the study they cite from using the short-acting bronchodilators, and what it ultimately says is that in most cases, this is self-resolving by around the 20-day mark,” said Dr. Liang. “Our advice is just to err on the side of caution and just provide that information piece to the patient.”
 

‘Significant Nuance’

Imran Satia, MD, assistant professor of respirology at McMaster University in Hamilton, Ontario, Canada, agreed that “most people who get a viral or bacterial upper or lower respiratory tract infection will get better with time, and there is very little evidence that giving steroids, antibiotics, or cough suppressants is better than waiting it out.” There is “significant nuance” in how to manage this situation, however.

“In some patients with underlying lung disease like asthma or COPD, increasing the frequency of regular inhaled steroids, bronchodilators, oral steroids, antibiotics, and chest imaging with breathing tests may be clinically warranted, and many physicians will do this,” he told this news organization. “In some patients with refractory chronic cough, there is no underlying identifiable disease, despite completing the necessary investigations. Or coughing persists despite trials of treatment for lung diseases, nasal diseases, and stomach reflux disease. This is commonly described as cough hypersensitivity syndrome, for which therapies targeting the neuronal pathways that control coughing are needed.”

Physicians should occasionally consider trying a temporary course of a short-acting bronchodilator inhaler, said Nicholas Vozoris, MD, assistant professor and clinician investigator in respirology at the University of Toronto, Toronto, Ontario, Canada. “I think that would be a reasonable first step in a case of really bad postinfectious cough,” he told this news organization. “But in general, drug treatments are not indicated.”
 

Environmental Concerns

Yet some things should raise clinicians’ suspicion of more complex issues.

“A pattern of recurrent colds or bronchitis with protracted coughing afterward raises strong suspicion for asthma, which can present as repeated, prolonged respiratory exacerbations,” he said. “Unless asthma is treated with appropriate inhaler therapy on a regular basis, it will unlikely come under control.”

Dr. Vozoris added that the environmental concerns over the use of metered dose inhalers (MDIs) are minimal compared with the other sources of pollution and the risks for undertreatment. “The authors are overplaying the environmental impact of MDI, in my opinion,” he said. “Physicians already have to deal with the challenging issue of suboptimal patient adherence to inhalers, and I fear that such comments may further drive that up. Furthermore, there is also an environmental footprint with not using inhalers, as patients can then experience suboptimally controlled lung disease as a result — and then present to the ER and get admitted to hospital for exacerbations of disease, where more resources and medications are used up.”

“In addition, in patients who are immunocompromised, protracted coughing after what was thought to be a cold may be associated with an “atypical” respiratory infection, such as tuberculosis, that will require special medical treatment,” Dr. Vozoris concluded.

No funding for the review of postinfectious cough was reported. Dr. Liang and Dr. Vozoris disclosed no competing interests. Dr. Satia reported receiving funding from the ERS Respire 3 Fellowship Award, BMA James Trust Award, North-West Lung Centre Charity (Manchester), NIHR CRF Manchester, Merck MSD, AstraZeneca, and GSK. Dr. Satia also has received consulting fees from Merck MSD, Genentech, and Respiplus; as well as speaker fees from AstraZeneca, GSK, Merck MSD, Sanofi-Regeneron. Satia has served on the following task force committees: Chronic Cough (ERS), Asthma Diagnosis and Management (ERS), NEUROCOUGH (ERS CRC), and the CTS Chronic Cough working group.

A version of this article appeared on Medscape.com.

Lingering postinfectious cough has been a concern across Canada this winter. Patients with this symptom (defined as a subacute cough, with symptoms lasting between 3 and 8 weeks after the infection) have many questions when they come to the clinic. But there is no evidence supporting pharmacologic treatment for postinfectious cough, according to an overview published on February 12 in the Canadian Medical Association Journal

“It’s something a lot of patients are worried about: That lingering cough after a common cold or flu,” lead author Kevin Liang, MD, of the Department of Family Medicine at The University of British Columbia in Vancouver, British Columbia, Canada, told this news organization. He added that some studies show that as much as a quarter of adult patients have this complaint.

Dr. Liang and his colleagues emphasized that the diagnosis of postinfectious cough is one of exclusion. It relies on the absence of concerning physical examination findings and other “subacute cough mimics” such as asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease, or use of angiotensin-converting enzyme inhibitors.

“Pertussis should be considered in patients with a paroxysmal cough, post-tussive vomiting, and inspiratory whoop,” they added. Coughs that persist beyond 8 weeks warrant further workup such as a pulmonary function test to rule out asthma or COPD. Coughs accompanied by hemoptysis, systemic symptoms, dysphagia, excessive dyspnea, or hoarseness also warrant further workup, they added. And patients with a history of smoking or recurrent pneumonia should be followed more closely.

In the absence of red flags, Dr. Liang and coauthors advised that there is no evidence supporting pharmacologic treatment, “which is associated with harms,” such as medication adverse effects, cost, strain on the medical supply chain, and the fact that pressurized metered-dose inhalers emit powerful greenhouse gases. “A lot of patients come in looking for solutions, but really, all the evidence says the over-the-counter cough syrup just doesn’t work. Or I see clinicians prescribing inhalers or different medication that can cost hundreds of dollars, and their efficacy, at least from the literature, shows that there’s really no improvement. Time and patience are the two keys to solving this,” Dr. Liang told this news organization.

Moreover, there is a distinct absence of guidelines on this topic. The College of Family Physicians of Canada’s recent literature review cited limited data supporting a trial of inhaled corticosteroids, a bronchodilator such as ipratropium-salbutamol, or an intranasal steroid if postnasal drip is suspected. However, “there’s a high risk of bias in the study they cite from using the short-acting bronchodilators, and what it ultimately says is that in most cases, this is self-resolving by around the 20-day mark,” said Dr. Liang. “Our advice is just to err on the side of caution and just provide that information piece to the patient.”
 

‘Significant Nuance’

Imran Satia, MD, assistant professor of respirology at McMaster University in Hamilton, Ontario, Canada, agreed that “most people who get a viral or bacterial upper or lower respiratory tract infection will get better with time, and there is very little evidence that giving steroids, antibiotics, or cough suppressants is better than waiting it out.” There is “significant nuance” in how to manage this situation, however.

“In some patients with underlying lung disease like asthma or COPD, increasing the frequency of regular inhaled steroids, bronchodilators, oral steroids, antibiotics, and chest imaging with breathing tests may be clinically warranted, and many physicians will do this,” he told this news organization. “In some patients with refractory chronic cough, there is no underlying identifiable disease, despite completing the necessary investigations. Or coughing persists despite trials of treatment for lung diseases, nasal diseases, and stomach reflux disease. This is commonly described as cough hypersensitivity syndrome, for which therapies targeting the neuronal pathways that control coughing are needed.”

Physicians should occasionally consider trying a temporary course of a short-acting bronchodilator inhaler, said Nicholas Vozoris, MD, assistant professor and clinician investigator in respirology at the University of Toronto, Toronto, Ontario, Canada. “I think that would be a reasonable first step in a case of really bad postinfectious cough,” he told this news organization. “But in general, drug treatments are not indicated.”
 

Environmental Concerns

Yet some things should raise clinicians’ suspicion of more complex issues.

“A pattern of recurrent colds or bronchitis with protracted coughing afterward raises strong suspicion for asthma, which can present as repeated, prolonged respiratory exacerbations,” he said. “Unless asthma is treated with appropriate inhaler therapy on a regular basis, it will unlikely come under control.”

Dr. Vozoris added that the environmental concerns over the use of metered dose inhalers (MDIs) are minimal compared with the other sources of pollution and the risks for undertreatment. “The authors are overplaying the environmental impact of MDI, in my opinion,” he said. “Physicians already have to deal with the challenging issue of suboptimal patient adherence to inhalers, and I fear that such comments may further drive that up. Furthermore, there is also an environmental footprint with not using inhalers, as patients can then experience suboptimally controlled lung disease as a result — and then present to the ER and get admitted to hospital for exacerbations of disease, where more resources and medications are used up.”

“In addition, in patients who are immunocompromised, protracted coughing after what was thought to be a cold may be associated with an “atypical” respiratory infection, such as tuberculosis, that will require special medical treatment,” Dr. Vozoris concluded.

No funding for the review of postinfectious cough was reported. Dr. Liang and Dr. Vozoris disclosed no competing interests. Dr. Satia reported receiving funding from the ERS Respire 3 Fellowship Award, BMA James Trust Award, North-West Lung Centre Charity (Manchester), NIHR CRF Manchester, Merck MSD, AstraZeneca, and GSK. Dr. Satia also has received consulting fees from Merck MSD, Genentech, and Respiplus; as well as speaker fees from AstraZeneca, GSK, Merck MSD, Sanofi-Regeneron. Satia has served on the following task force committees: Chronic Cough (ERS), Asthma Diagnosis and Management (ERS), NEUROCOUGH (ERS CRC), and the CTS Chronic Cough working group.

A version of this article appeared on Medscape.com.

Jake Warn calls vaping “a toxic artificial love.”

Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.

He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.

“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.

Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.

Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.

But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.

“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”

A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.

Mrs. Warn noticed changes off the field, too.

“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”

Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.

Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.

Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.

Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.

“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.

For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.

Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.

Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”

One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.

“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.

The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.

The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.

But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.

Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”

Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.

“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.

Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.

“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.

Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.

“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”

But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.

“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
 

Will vaping be a ‘phase?’

Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.

“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”

But his mother said quitting may not be that simple.

“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”

Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Jake Warn calls vaping “a toxic artificial love.”

Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.

He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.

“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.

Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.

Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.

But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.

“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”

A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.

Mrs. Warn noticed changes off the field, too.

“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”

Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.

Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.

Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.

Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.

“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.

For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.

Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.

Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”

One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.

“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.

The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.

The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.

But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.

Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”

Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.

“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.

Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.

“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.

Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.

“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”

But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.

“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
 

Will vaping be a ‘phase?’

Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.

“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”

But his mother said quitting may not be that simple.

“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”

Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

Jake Warn calls vaping “a toxic artificial love.”

Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.

He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.

“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.

Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.

Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.

But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.

“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”

A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.

Mrs. Warn noticed changes off the field, too.

“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”

Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.

Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.

Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.

Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.

“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.

For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.

Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.

Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”

One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.

“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.

The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.

The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.

But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.

Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”

Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.

“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.

Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.

“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.

Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.

“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”

But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.

“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
 

Will vaping be a ‘phase?’

Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.

“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”

But his mother said quitting may not be that simple.

“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”

Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – In the international FREEDOM COVID trial that randomized non–critically ill hospitalized patients, a therapeutic dose of anticoagulation relative to a prophylactic dose significantly reduced death from COVID-19 at 30 days, even as a larger composite primary endpoint was missed.

The mortality reduction suggests therapeutic-dose anticoagulation “may improve outcomes in non–critically ill patients hospitalized with COVID-19 who are at increased risk for adverse events but do not yet require ICU-level of care,” reported Valentin Fuster, MD, PhD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Fuster_Valentin_ACC2023_web.JPG

These data provide a suggestion rather than a demonstration of benefit because the primary composite endpoint of all-cause mortality, intubation requiring mechanical ventilation, systemic thromboembolism or ischemic stroke at 30 days was not met. Although this 30-day outcome was lower on the therapeutic dose (11.3% vs. 13.2%), the difference was only a trend (hazard ratio, 0.85; P = .11), said Dr. Fuster, physician-in-chief, Mount Sinai Hospital, New York.
 

Missed primary endpoint blamed on low events

The declining severity of more recent COVID-19 variants (the trial was conducted from August 2022 to September 2022) might be one explanation that the primary endpoint was not met, but the more likely explanation is the relatively good health status – and therefore a low risk of events – among patients randomized in India, 1 of 10 participating countries.

India accounted for roughly 40% of the total number of 3,398 patients in the intention-to-treat population. In India, the rates of events were 0.7 and 1.3 in the prophylactic and therapeutic anticoagulation arms, respectively. In contrast, they were 17.5 and 9.5, respectively in the United States. In combined data from the other eight countries, the rates were 22.78 and 20.4, respectively.

“These results emphasize that varying country-specific thresholds for hospitalization may affect patient prognosis and the potential utility of advanced therapies” Dr. Fuster said.

In fact, the therapeutic anticoagulation was linked to a nonsignificant twofold increase in the risk of the primary outcome in India (HR, 2.01; 95% confidence interval, 0.57-7.13) when outcomes were stratified by country. In the United States, where there was a much higher incidence of events, therapeutic anticoagulation was associated with a nearly 50% reduction (HR, 0.53; 95% CI, 0.31-0.91).

In the remaining countries, which included those in Latin America and Europe as well as the city of Hong Kong, the primary outcome was reduced numerically but not statistically by therapeutic relative to prophylactic anticoagulation (HR, 0.89; 95% CI, 0.71-1.11).
 

Enoxaparin and apixaban are studied

In FREEDOM COVID, patients were randomized to a therapeutic dose of the low-molecular-weight heparin (LMWH) enoxaparin (1 mg/kg every 12 hours), a prophylactic dose of enoxaparin (40 mg once daily), or a therapeutic dose of the direct factor Xa inhibitor apixaban (5 mg every 12 hours). Lower doses of enoxaparin and apixaban were used for those with renal impairment, and lower doses of apixaban were employed for elderly patients (≥ 80 years) and those with low body weight (≤ 60 kg).

The major inclusion criteria were confirmed COVID-19 infection with symptomatic systemic involvement. The major exclusion criteria were need for ICU level of care or active bleeding.

The therapeutic anticoagulation arms performed similarly and were combined for comparison to the prophylactic arm. Despite the failure to show a difference in the primary outcome, the rate of 30-day mortality was substantially lower in the therapeutic arm (4.9% vs. 7.0%), translating into a 30% risk reduction (HR, 0.70; P = .01).

Therapeutic anticoagulation was also associated with a lower rate of intubation/mechanical ventilation (6.4% vs. 8.4%) that reached statistical significance (HR, 0.75; P = .03). The risk reduction was also significant for a combination of these endpoints (HR, 0.77; P = .03).

The lower proportion of patients who eventually required ICU-level of care (9.9% vs. 11.7%) showed a trend in favor of therapeutic anticoagulation (HR, 0.84; P = .11).
 

Bleeding rates did not differ between arms

Bleeding Academic Research Consortium major bleeding types 3 and 5 were slightly numerically higher in the group randomized to therapeutic enoxaparin (0.5%) than prophylactic enoxaparin (0.1%) and therapeutic apixaban (0.3%), but the differences between any groups were not significant.

Numerous anticoagulation trials in patients with COVID-19 have been published previously. One 2021 trial published in the New England Journal of Medicine also suggested benefit from a therapeutic relative to prophylactic anticoagulation. In that trial, which compared heparin to usual-care thromboprophylaxis, benefits were derived from a Bayesian analysis. Significant differences were not shown for death or other major outcome assessed individually.

Even though this more recent trial missed its primary endpoint, Gregg Stone, MD, a coauthor of this study and a colleague of Dr. Fuster at the Mount Sinai School of Medicine, New York, reiterated that these results support routine anticoagulation in hospitalized COVID-19 patients.

“These are robust reductions in mortality and intubation rates, which are the most serious outcomes,” said Dr. Stone, who is first author of the paper, which was published in the Journal of the American College of Cardiology immediately after Dr. Fuster’s presentation.

COVID-19 has proven to be a very thrombogenic virus, but the literature has not been wholly consistent on which anticoagulation treatment provides the best balance of benefits and risks, according to Julia Grapsa, MD, PhD, attending cardiologist, Guys and St. Thomas Hospital, London. She said that this randomized trial, despite its failure to meet the primary endpoint, is useful.

“This demonstrates that a therapeutic dose of enoxaparin is likely to improve outcomes over a prophylactic dose with a low risk of bleeding,” Dr. Grapsa said. On the basis of the randomized study, “I feel more confident with this approach.”

Dr. Fuster reported no potential conflicts of interest. Dr. Stone has financial relationships with more than 30 companies that make pharmaceuticals and medical devices. Dr. Grapsa reported no potential conflicts of interest.

NEW ORLEANS – In the international FREEDOM COVID trial that randomized non–critically ill hospitalized patients, a therapeutic dose of anticoagulation relative to a prophylactic dose significantly reduced death from COVID-19 at 30 days, even as a larger composite primary endpoint was missed.

The mortality reduction suggests therapeutic-dose anticoagulation “may improve outcomes in non–critically ill patients hospitalized with COVID-19 who are at increased risk for adverse events but do not yet require ICU-level of care,” reported Valentin Fuster, MD, PhD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Fuster_Valentin_ACC2023_web.JPG

These data provide a suggestion rather than a demonstration of benefit because the primary composite endpoint of all-cause mortality, intubation requiring mechanical ventilation, systemic thromboembolism or ischemic stroke at 30 days was not met. Although this 30-day outcome was lower on the therapeutic dose (11.3% vs. 13.2%), the difference was only a trend (hazard ratio, 0.85; P = .11), said Dr. Fuster, physician-in-chief, Mount Sinai Hospital, New York.
 

Missed primary endpoint blamed on low events

The declining severity of more recent COVID-19 variants (the trial was conducted from August 2022 to September 2022) might be one explanation that the primary endpoint was not met, but the more likely explanation is the relatively good health status – and therefore a low risk of events – among patients randomized in India, 1 of 10 participating countries.

India accounted for roughly 40% of the total number of 3,398 patients in the intention-to-treat population. In India, the rates of events were 0.7 and 1.3 in the prophylactic and therapeutic anticoagulation arms, respectively. In contrast, they were 17.5 and 9.5, respectively in the United States. In combined data from the other eight countries, the rates were 22.78 and 20.4, respectively.

“These results emphasize that varying country-specific thresholds for hospitalization may affect patient prognosis and the potential utility of advanced therapies” Dr. Fuster said.

In fact, the therapeutic anticoagulation was linked to a nonsignificant twofold increase in the risk of the primary outcome in India (HR, 2.01; 95% confidence interval, 0.57-7.13) when outcomes were stratified by country. In the United States, where there was a much higher incidence of events, therapeutic anticoagulation was associated with a nearly 50% reduction (HR, 0.53; 95% CI, 0.31-0.91).

In the remaining countries, which included those in Latin America and Europe as well as the city of Hong Kong, the primary outcome was reduced numerically but not statistically by therapeutic relative to prophylactic anticoagulation (HR, 0.89; 95% CI, 0.71-1.11).
 

Enoxaparin and apixaban are studied

In FREEDOM COVID, patients were randomized to a therapeutic dose of the low-molecular-weight heparin (LMWH) enoxaparin (1 mg/kg every 12 hours), a prophylactic dose of enoxaparin (40 mg once daily), or a therapeutic dose of the direct factor Xa inhibitor apixaban (5 mg every 12 hours). Lower doses of enoxaparin and apixaban were used for those with renal impairment, and lower doses of apixaban were employed for elderly patients (≥ 80 years) and those with low body weight (≤ 60 kg).

The major inclusion criteria were confirmed COVID-19 infection with symptomatic systemic involvement. The major exclusion criteria were need for ICU level of care or active bleeding.

The therapeutic anticoagulation arms performed similarly and were combined for comparison to the prophylactic arm. Despite the failure to show a difference in the primary outcome, the rate of 30-day mortality was substantially lower in the therapeutic arm (4.9% vs. 7.0%), translating into a 30% risk reduction (HR, 0.70; P = .01).

Therapeutic anticoagulation was also associated with a lower rate of intubation/mechanical ventilation (6.4% vs. 8.4%) that reached statistical significance (HR, 0.75; P = .03). The risk reduction was also significant for a combination of these endpoints (HR, 0.77; P = .03).

The lower proportion of patients who eventually required ICU-level of care (9.9% vs. 11.7%) showed a trend in favor of therapeutic anticoagulation (HR, 0.84; P = .11).
 

Bleeding rates did not differ between arms

Bleeding Academic Research Consortium major bleeding types 3 and 5 were slightly numerically higher in the group randomized to therapeutic enoxaparin (0.5%) than prophylactic enoxaparin (0.1%) and therapeutic apixaban (0.3%), but the differences between any groups were not significant.

Numerous anticoagulation trials in patients with COVID-19 have been published previously. One 2021 trial published in the New England Journal of Medicine also suggested benefit from a therapeutic relative to prophylactic anticoagulation. In that trial, which compared heparin to usual-care thromboprophylaxis, benefits were derived from a Bayesian analysis. Significant differences were not shown for death or other major outcome assessed individually.

Even though this more recent trial missed its primary endpoint, Gregg Stone, MD, a coauthor of this study and a colleague of Dr. Fuster at the Mount Sinai School of Medicine, New York, reiterated that these results support routine anticoagulation in hospitalized COVID-19 patients.

“These are robust reductions in mortality and intubation rates, which are the most serious outcomes,” said Dr. Stone, who is first author of the paper, which was published in the Journal of the American College of Cardiology immediately after Dr. Fuster’s presentation.

COVID-19 has proven to be a very thrombogenic virus, but the literature has not been wholly consistent on which anticoagulation treatment provides the best balance of benefits and risks, according to Julia Grapsa, MD, PhD, attending cardiologist, Guys and St. Thomas Hospital, London. She said that this randomized trial, despite its failure to meet the primary endpoint, is useful.

“This demonstrates that a therapeutic dose of enoxaparin is likely to improve outcomes over a prophylactic dose with a low risk of bleeding,” Dr. Grapsa said. On the basis of the randomized study, “I feel more confident with this approach.”

Dr. Fuster reported no potential conflicts of interest. Dr. Stone has financial relationships with more than 30 companies that make pharmaceuticals and medical devices. Dr. Grapsa reported no potential conflicts of interest.

NEW ORLEANS – In the international FREEDOM COVID trial that randomized non–critically ill hospitalized patients, a therapeutic dose of anticoagulation relative to a prophylactic dose significantly reduced death from COVID-19 at 30 days, even as a larger composite primary endpoint was missed.

The mortality reduction suggests therapeutic-dose anticoagulation “may improve outcomes in non–critically ill patients hospitalized with COVID-19 who are at increased risk for adverse events but do not yet require ICU-level of care,” reported Valentin Fuster, MD, PhD, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Fuster_Valentin_ACC2023_web.JPG

These data provide a suggestion rather than a demonstration of benefit because the primary composite endpoint of all-cause mortality, intubation requiring mechanical ventilation, systemic thromboembolism or ischemic stroke at 30 days was not met. Although this 30-day outcome was lower on the therapeutic dose (11.3% vs. 13.2%), the difference was only a trend (hazard ratio, 0.85; P = .11), said Dr. Fuster, physician-in-chief, Mount Sinai Hospital, New York.
 

Missed primary endpoint blamed on low events

The declining severity of more recent COVID-19 variants (the trial was conducted from August 2022 to September 2022) might be one explanation that the primary endpoint was not met, but the more likely explanation is the relatively good health status – and therefore a low risk of events – among patients randomized in India, 1 of 10 participating countries.

India accounted for roughly 40% of the total number of 3,398 patients in the intention-to-treat population. In India, the rates of events were 0.7 and 1.3 in the prophylactic and therapeutic anticoagulation arms, respectively. In contrast, they were 17.5 and 9.5, respectively in the United States. In combined data from the other eight countries, the rates were 22.78 and 20.4, respectively.

“These results emphasize that varying country-specific thresholds for hospitalization may affect patient prognosis and the potential utility of advanced therapies” Dr. Fuster said.

In fact, the therapeutic anticoagulation was linked to a nonsignificant twofold increase in the risk of the primary outcome in India (HR, 2.01; 95% confidence interval, 0.57-7.13) when outcomes were stratified by country. In the United States, where there was a much higher incidence of events, therapeutic anticoagulation was associated with a nearly 50% reduction (HR, 0.53; 95% CI, 0.31-0.91).

In the remaining countries, which included those in Latin America and Europe as well as the city of Hong Kong, the primary outcome was reduced numerically but not statistically by therapeutic relative to prophylactic anticoagulation (HR, 0.89; 95% CI, 0.71-1.11).
 

Enoxaparin and apixaban are studied

In FREEDOM COVID, patients were randomized to a therapeutic dose of the low-molecular-weight heparin (LMWH) enoxaparin (1 mg/kg every 12 hours), a prophylactic dose of enoxaparin (40 mg once daily), or a therapeutic dose of the direct factor Xa inhibitor apixaban (5 mg every 12 hours). Lower doses of enoxaparin and apixaban were used for those with renal impairment, and lower doses of apixaban were employed for elderly patients (≥ 80 years) and those with low body weight (≤ 60 kg).

The major inclusion criteria were confirmed COVID-19 infection with symptomatic systemic involvement. The major exclusion criteria were need for ICU level of care or active bleeding.

The therapeutic anticoagulation arms performed similarly and were combined for comparison to the prophylactic arm. Despite the failure to show a difference in the primary outcome, the rate of 30-day mortality was substantially lower in the therapeutic arm (4.9% vs. 7.0%), translating into a 30% risk reduction (HR, 0.70; P = .01).

Therapeutic anticoagulation was also associated with a lower rate of intubation/mechanical ventilation (6.4% vs. 8.4%) that reached statistical significance (HR, 0.75; P = .03). The risk reduction was also significant for a combination of these endpoints (HR, 0.77; P = .03).

The lower proportion of patients who eventually required ICU-level of care (9.9% vs. 11.7%) showed a trend in favor of therapeutic anticoagulation (HR, 0.84; P = .11).
 

Bleeding rates did not differ between arms

Bleeding Academic Research Consortium major bleeding types 3 and 5 were slightly numerically higher in the group randomized to therapeutic enoxaparin (0.5%) than prophylactic enoxaparin (0.1%) and therapeutic apixaban (0.3%), but the differences between any groups were not significant.

Numerous anticoagulation trials in patients with COVID-19 have been published previously. One 2021 trial published in the New England Journal of Medicine also suggested benefit from a therapeutic relative to prophylactic anticoagulation. In that trial, which compared heparin to usual-care thromboprophylaxis, benefits were derived from a Bayesian analysis. Significant differences were not shown for death or other major outcome assessed individually.

Even though this more recent trial missed its primary endpoint, Gregg Stone, MD, a coauthor of this study and a colleague of Dr. Fuster at the Mount Sinai School of Medicine, New York, reiterated that these results support routine anticoagulation in hospitalized COVID-19 patients.

“These are robust reductions in mortality and intubation rates, which are the most serious outcomes,” said Dr. Stone, who is first author of the paper, which was published in the Journal of the American College of Cardiology immediately after Dr. Fuster’s presentation.

COVID-19 has proven to be a very thrombogenic virus, but the literature has not been wholly consistent on which anticoagulation treatment provides the best balance of benefits and risks, according to Julia Grapsa, MD, PhD, attending cardiologist, Guys and St. Thomas Hospital, London. She said that this randomized trial, despite its failure to meet the primary endpoint, is useful.

“This demonstrates that a therapeutic dose of enoxaparin is likely to improve outcomes over a prophylactic dose with a low risk of bleeding,” Dr. Grapsa said. On the basis of the randomized study, “I feel more confident with this approach.”

Dr. Fuster reported no potential conflicts of interest. Dr. Stone has financial relationships with more than 30 companies that make pharmaceuticals and medical devices. Dr. Grapsa reported no potential conflicts of interest.

Already commonly used in combination for the treatment of pulmonary arterial hypertension (PAH), macitentan and tadalafil are safe and effective in a fixed-dose combination even as first-line therapy, according to a randomized multicenter comparative trial.

The fixed-dose combination “led to a highly significant and marked improvement in pulmonary vascular resistance when compared to macitentan and tadalafil as monotherapies,” Kelly Chin, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Chin_Kelly_ACC2023_web.JPG

Guidelines encourage rapid PVR reductions

In practice, it is common to start treatment with either the endothelial receptor antagonist (ERA) macitentan, the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, or other frequently used medications for PAH, and to then add additional treatments, according to Dr. Chin. She pointed out, however, that guidelines, including those issued jointly by the European Society of Cardiology and the European Respiratory Society, encourage rapid escalation of therapy to quickly lower pulmonary vascular resistance (PVR).

In general, both macitentan and tadalafil are well tolerated, but the advantage and the safety of rapidly reducing PVR when these are initiated together in a single pill had not been evaluated previously in a major trial. In this double-blind phase III trial, called A DUE, 187 patients in functional class II or III PAH were randomized. The three-arm study included both treatment naive patients and patients who had been on stable doses (> 3 months) of an ERA or a PDE5 inhibitor, explained Dr. Chin, director of pulmonary hypertension at the UT Southwestern, Dallas.

Treatment naive patients, representing about 53% of the study population, were randomized to 10 mg macitentan monotherapy, 40 mg tadalafil monotherapy, or a fixed-dose, single-pill combination containing both. If on a stable dose of an ERA at trial entry, patients were randomized to 10 macitentan as a monotherapy or to the fixed dose combination. Patients entering the trial already on a stable dose of a PDE5 inhibitor were randomized to 40 mg tadalafil or the combination.
 

PVR reduced twofold on combination therapy

Relative to macitentan monotherapy, the percentage change from baseline in PVR by ratio of geometric mean, which was the primary outcome, was about twice as high on the combination (45% vs. 23%) at the end of the 16-week trial. This translates into a 29% PVR reduction (hazard ratio, 0.71; P < .0001).

For combination therapy relative to tadalafil monotherapy, the advantage for the fixed dose combination (44% vs. 22%) was about the same, also providing a nearly 30% relative reduction (HR, 0.72; P < .0001).

The increases in 6-minute walk distance (6MWD) at 16 weeks, a secondary endpoint, numerically favored the combination pill over both macitentan monotherapy (52.9 vs. 39.5 meters; P = .38) and tadalafil (43.4 vs. 15.9 meters; P = .059), but only the improvement relative to tadalafil monotherapy was considered a trend.

The proportion of patients who experienced at least one serious adverse event was higher in the combination arm (14.0%) relative to single agent macitentan (8.6%) or single agent tadalafil (9.1%). The adverse events and serious adverse events more common on the combination included hypotension, fluid retention, and anemia. This latter side effect occurred in 18.7%, 2.9%, and 2.3% in the combination, macitentan monotherapy, and tadalafil arms, respectively.

Several of those invited by the ACC to discuss the paper, including Lee R. Goldberg, MD, section chief of advanced heart failure and cardiac transplant, University of Pennsylvania, Philadelphia, raised concern about the increased rate of anemia among those in the combination pill. Two of the patients (2%) treated with the combination developed a hemoglobin < 8 g/dL.

Overall, nine (8.4%) of those on the fixed-dose combination, two (4.5%) of those randomized to tadalafil monotherapy, and none of the patients randomized to macitentan discontinued therapy due to side effects.
 

Anemia risk unexpected

Based on “the unexpected signal of an anemia risk,” Biykem Bozkurt, MD, PhD, chair of cardiology at Baylor College of Medicine, Houston, said that a larger scale trial with a longer follow-up is needed. While the concept of front-loading two drugs is attractive “for the very challenging PAH population,” she called for further evaluation of this safety signal before clinicians switch from the current practice of starting with one PAH therapy before adding others.

Bozkurt_Biykem_ACC2023_web.JPG

In addition, Dr. Bozkurt said a more definitive study would be helpful in determining whether starting with a fixed-pill combination is better than sequential treatment to improve quality of life. Dr. Bozkurt said it is likely that the lack of significant benefit on 6MWD in this study was due to the relatively small sample size, but an improvement in this measure would be another reason to consider a front-line fixed-dose combination.

Dr. Chin, in an interview, did not agree. She agreed that a larger sample size might have yielded a significant improvement in 6MWD, but she noted this outcome was moving in the right direction and was not the primary endpoint. In her opinion, this phase 3 trial does confirm that fixed-dose combination is well tolerated, has acceptable safety, and markedly improves PVR, fulfilling the guideline goal of controlling PAH more quickly.

Dr. Chin reports financial relationships with Altavant, Arena, Gossamer Bio, Janssen, Merck, ShouTi, and United Therapeutics. Dr. Goldberg reports financial relationships with Abbott, Respicardia/Zoll, and Viscardia. Dr. Bozkurt reports financial relationships with Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cardurion, LivaNova, Relypsa, Renovacor, Sanofi-Aventis, and Vifor.

Already commonly used in combination for the treatment of pulmonary arterial hypertension (PAH), macitentan and tadalafil are safe and effective in a fixed-dose combination even as first-line therapy, according to a randomized multicenter comparative trial.

The fixed-dose combination “led to a highly significant and marked improvement in pulmonary vascular resistance when compared to macitentan and tadalafil as monotherapies,” Kelly Chin, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Chin_Kelly_ACC2023_web.JPG

Guidelines encourage rapid PVR reductions

In practice, it is common to start treatment with either the endothelial receptor antagonist (ERA) macitentan, the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, or other frequently used medications for PAH, and to then add additional treatments, according to Dr. Chin. She pointed out, however, that guidelines, including those issued jointly by the European Society of Cardiology and the European Respiratory Society, encourage rapid escalation of therapy to quickly lower pulmonary vascular resistance (PVR).

In general, both macitentan and tadalafil are well tolerated, but the advantage and the safety of rapidly reducing PVR when these are initiated together in a single pill had not been evaluated previously in a major trial. In this double-blind phase III trial, called A DUE, 187 patients in functional class II or III PAH were randomized. The three-arm study included both treatment naive patients and patients who had been on stable doses (> 3 months) of an ERA or a PDE5 inhibitor, explained Dr. Chin, director of pulmonary hypertension at the UT Southwestern, Dallas.

Treatment naive patients, representing about 53% of the study population, were randomized to 10 mg macitentan monotherapy, 40 mg tadalafil monotherapy, or a fixed-dose, single-pill combination containing both. If on a stable dose of an ERA at trial entry, patients were randomized to 10 macitentan as a monotherapy or to the fixed dose combination. Patients entering the trial already on a stable dose of a PDE5 inhibitor were randomized to 40 mg tadalafil or the combination.
 

PVR reduced twofold on combination therapy

Relative to macitentan monotherapy, the percentage change from baseline in PVR by ratio of geometric mean, which was the primary outcome, was about twice as high on the combination (45% vs. 23%) at the end of the 16-week trial. This translates into a 29% PVR reduction (hazard ratio, 0.71; P < .0001).

For combination therapy relative to tadalafil monotherapy, the advantage for the fixed dose combination (44% vs. 22%) was about the same, also providing a nearly 30% relative reduction (HR, 0.72; P < .0001).

The increases in 6-minute walk distance (6MWD) at 16 weeks, a secondary endpoint, numerically favored the combination pill over both macitentan monotherapy (52.9 vs. 39.5 meters; P = .38) and tadalafil (43.4 vs. 15.9 meters; P = .059), but only the improvement relative to tadalafil monotherapy was considered a trend.

The proportion of patients who experienced at least one serious adverse event was higher in the combination arm (14.0%) relative to single agent macitentan (8.6%) or single agent tadalafil (9.1%). The adverse events and serious adverse events more common on the combination included hypotension, fluid retention, and anemia. This latter side effect occurred in 18.7%, 2.9%, and 2.3% in the combination, macitentan monotherapy, and tadalafil arms, respectively.

Several of those invited by the ACC to discuss the paper, including Lee R. Goldberg, MD, section chief of advanced heart failure and cardiac transplant, University of Pennsylvania, Philadelphia, raised concern about the increased rate of anemia among those in the combination pill. Two of the patients (2%) treated with the combination developed a hemoglobin < 8 g/dL.

Overall, nine (8.4%) of those on the fixed-dose combination, two (4.5%) of those randomized to tadalafil monotherapy, and none of the patients randomized to macitentan discontinued therapy due to side effects.
 

Anemia risk unexpected

Based on “the unexpected signal of an anemia risk,” Biykem Bozkurt, MD, PhD, chair of cardiology at Baylor College of Medicine, Houston, said that a larger scale trial with a longer follow-up is needed. While the concept of front-loading two drugs is attractive “for the very challenging PAH population,” she called for further evaluation of this safety signal before clinicians switch from the current practice of starting with one PAH therapy before adding others.

Bozkurt_Biykem_ACC2023_web.JPG

In addition, Dr. Bozkurt said a more definitive study would be helpful in determining whether starting with a fixed-pill combination is better than sequential treatment to improve quality of life. Dr. Bozkurt said it is likely that the lack of significant benefit on 6MWD in this study was due to the relatively small sample size, but an improvement in this measure would be another reason to consider a front-line fixed-dose combination.

Dr. Chin, in an interview, did not agree. She agreed that a larger sample size might have yielded a significant improvement in 6MWD, but she noted this outcome was moving in the right direction and was not the primary endpoint. In her opinion, this phase 3 trial does confirm that fixed-dose combination is well tolerated, has acceptable safety, and markedly improves PVR, fulfilling the guideline goal of controlling PAH more quickly.

Dr. Chin reports financial relationships with Altavant, Arena, Gossamer Bio, Janssen, Merck, ShouTi, and United Therapeutics. Dr. Goldberg reports financial relationships with Abbott, Respicardia/Zoll, and Viscardia. Dr. Bozkurt reports financial relationships with Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cardurion, LivaNova, Relypsa, Renovacor, Sanofi-Aventis, and Vifor.

Already commonly used in combination for the treatment of pulmonary arterial hypertension (PAH), macitentan and tadalafil are safe and effective in a fixed-dose combination even as first-line therapy, according to a randomized multicenter comparative trial.

The fixed-dose combination “led to a highly significant and marked improvement in pulmonary vascular resistance when compared to macitentan and tadalafil as monotherapies,” Kelly Chin, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Chin_Kelly_ACC2023_web.JPG

Guidelines encourage rapid PVR reductions

In practice, it is common to start treatment with either the endothelial receptor antagonist (ERA) macitentan, the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, or other frequently used medications for PAH, and to then add additional treatments, according to Dr. Chin. She pointed out, however, that guidelines, including those issued jointly by the European Society of Cardiology and the European Respiratory Society, encourage rapid escalation of therapy to quickly lower pulmonary vascular resistance (PVR).

In general, both macitentan and tadalafil are well tolerated, but the advantage and the safety of rapidly reducing PVR when these are initiated together in a single pill had not been evaluated previously in a major trial. In this double-blind phase III trial, called A DUE, 187 patients in functional class II or III PAH were randomized. The three-arm study included both treatment naive patients and patients who had been on stable doses (> 3 months) of an ERA or a PDE5 inhibitor, explained Dr. Chin, director of pulmonary hypertension at the UT Southwestern, Dallas.

Treatment naive patients, representing about 53% of the study population, were randomized to 10 mg macitentan monotherapy, 40 mg tadalafil monotherapy, or a fixed-dose, single-pill combination containing both. If on a stable dose of an ERA at trial entry, patients were randomized to 10 macitentan as a monotherapy or to the fixed dose combination. Patients entering the trial already on a stable dose of a PDE5 inhibitor were randomized to 40 mg tadalafil or the combination.
 

PVR reduced twofold on combination therapy

Relative to macitentan monotherapy, the percentage change from baseline in PVR by ratio of geometric mean, which was the primary outcome, was about twice as high on the combination (45% vs. 23%) at the end of the 16-week trial. This translates into a 29% PVR reduction (hazard ratio, 0.71; P < .0001).

For combination therapy relative to tadalafil monotherapy, the advantage for the fixed dose combination (44% vs. 22%) was about the same, also providing a nearly 30% relative reduction (HR, 0.72; P < .0001).

The increases in 6-minute walk distance (6MWD) at 16 weeks, a secondary endpoint, numerically favored the combination pill over both macitentan monotherapy (52.9 vs. 39.5 meters; P = .38) and tadalafil (43.4 vs. 15.9 meters; P = .059), but only the improvement relative to tadalafil monotherapy was considered a trend.

The proportion of patients who experienced at least one serious adverse event was higher in the combination arm (14.0%) relative to single agent macitentan (8.6%) or single agent tadalafil (9.1%). The adverse events and serious adverse events more common on the combination included hypotension, fluid retention, and anemia. This latter side effect occurred in 18.7%, 2.9%, and 2.3% in the combination, macitentan monotherapy, and tadalafil arms, respectively.

Several of those invited by the ACC to discuss the paper, including Lee R. Goldberg, MD, section chief of advanced heart failure and cardiac transplant, University of Pennsylvania, Philadelphia, raised concern about the increased rate of anemia among those in the combination pill. Two of the patients (2%) treated with the combination developed a hemoglobin < 8 g/dL.

Overall, nine (8.4%) of those on the fixed-dose combination, two (4.5%) of those randomized to tadalafil monotherapy, and none of the patients randomized to macitentan discontinued therapy due to side effects.
 

Anemia risk unexpected

Based on “the unexpected signal of an anemia risk,” Biykem Bozkurt, MD, PhD, chair of cardiology at Baylor College of Medicine, Houston, said that a larger scale trial with a longer follow-up is needed. While the concept of front-loading two drugs is attractive “for the very challenging PAH population,” she called for further evaluation of this safety signal before clinicians switch from the current practice of starting with one PAH therapy before adding others.

Bozkurt_Biykem_ACC2023_web.JPG

In addition, Dr. Bozkurt said a more definitive study would be helpful in determining whether starting with a fixed-pill combination is better than sequential treatment to improve quality of life. Dr. Bozkurt said it is likely that the lack of significant benefit on 6MWD in this study was due to the relatively small sample size, but an improvement in this measure would be another reason to consider a front-line fixed-dose combination.

Dr. Chin, in an interview, did not agree. She agreed that a larger sample size might have yielded a significant improvement in 6MWD, but she noted this outcome was moving in the right direction and was not the primary endpoint. In her opinion, this phase 3 trial does confirm that fixed-dose combination is well tolerated, has acceptable safety, and markedly improves PVR, fulfilling the guideline goal of controlling PAH more quickly.

Dr. Chin reports financial relationships with Altavant, Arena, Gossamer Bio, Janssen, Merck, ShouTi, and United Therapeutics. Dr. Goldberg reports financial relationships with Abbott, Respicardia/Zoll, and Viscardia. Dr. Bozkurt reports financial relationships with Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cardurion, LivaNova, Relypsa, Renovacor, Sanofi-Aventis, and Vifor.

Insomnia – difficulty falling or staying asleep – was associated with a 69% greater risk of having a myocardial infarction than among adults without insomnia, according to new research.

Those who slept 5 or fewer hours per night had the highest risk for MI, and those with both diabetes and insomnia had double the risk for MI, compared with patients without these comorbidities.

insomnia_senior_man_web.jpg

The findings are from a meta-analysis of studies in more than 1 million patients, almost all without prior MI who were, on average, in their early 50s and followed for 9 years.

Yomna E. Dean, a medical student at Alexandria (Egypt) University, reported these results in a press briefing, and the study was simultaneously published in Clinical Cardiology. It will be presented at the upcoming at the annual scientific sessions of the American College of Cardiology.

“Insomnia and ]at least] 5 hours of sleep are highly associated with increased incidence of MI, an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines,” the researchers concluded.

“We believe that [insomnia] should be screened and patients should be educated about the importance of sleep because nowadays insomnia is no longer a disease – sleep deprivation could also be a life choice,” Ms, Dean told a press conference prior to the meeting.

“Clinicians must educate the patients about the importance of sleep in maintaining a healthy heart and encourage proper sleep hygiene,” Ms. Dean reiterated in an email. “And if a patient still has insomnia, other methods should be considered such as cognitive-behavior[al] therapy for insomnia [CBT-I].”
 

Adds to growing evidence

This study does not allow any conclusion about whether treating insomnia will reduce heart attack risk, Jennifer L. Martin, PhD, president of the American Academy of Sleep Medicine, noted in a comment. Nor does it report the diversity of study participants, since insomnia is also a health equity issue, she noted, and insomnia symptoms and comorbidities were self-reported.

However, this analysis “adds to the growing evidence that poor quality or insufficient sleep is associated with poor health,” said Dr. Martin, professor of medicine at the University of California, Los Angeles, who was not involved with this research.

The study reinforces the recommendation from the American Heart Association, which includes “Get Healthy Sleep” as one of “Life’s Essential 8” for heart health, Dr. Martin noted.

“Particularly in primary care where disease prevention and health promotion are important, clinicians should be asking all patients about their sleep – just like they ask about diet and exercise – as a key aspect of maintaining heart health,” she said.

Advice about basic sleep hygiene advice is a first step, she noted.

When improved sleep hygiene is not enough to address chronic insomnia, the AASM’s clinical practice guidelines and the guidelines of the Department of Veterans Affairs/Department of Defense, recommend first-line treatment with CBT-I, typically offered by a sleep specialist or mental health clinician.

Similarly, the American College of Physicians suggests that sleeping pills should be reserved for short-term use in patients who may not benefit sufficiently from CBT-I.
 

Sleeping too little, too much, equally harmful

“Studies have found that insomnia and subsequent sleep deprivation puts the body under stress,” Ms. Dean said. “This triggers cortisol release which could accelerate atherosclerosis,” and increase risk of MI.

For this analysis, the researchers identified nine observational studies, published from 1998 to 2019, with data on incident MI in adults who had insomnia.

The diagnosis of insomnia was based on ICD diagnostic codes or on the DSM‐5, which defines insomnia as the presence of any of the following three symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep. Patients with sleep apnea were excluded.

The studies were in populations in China, Germany, Norway, Taiwan, United Kingdom, and United States, in 1.1 million adults aged 18 and older. The patients had a mean age of 52 years and 13% had insomnia.

During follow-up, 2,406 of 153,881 patients with insomnia, and 12,398 of 1,030,375 patients without insomnia had an MI.

In the pooled analysis, patients with insomnia had a significantly increased risk of MI (relative risk, 1.69; P < .00001), after adjusting for age, gender, diabetes, hypertension, high cholesterol, and smoking.

Sleeping 5 hours or less was associated with a greater risk for MI than sleeping 6 hours, or 7-8 hours, but sleeping 9 hours or more was just as harmful.

162409_graphic_web.png

Patients who had difficulty initiating and maintaining sleep – two symptoms of insomnia – had a 13% increased risk for MI compared with other patients (RR, 1.13; P = .003).

However, patients who had nonrestorative sleep and daytime dysfunction despite adequate sleep – which is common – did not have an increased risk of MI, compared with other patients (RR, 1.06; P = .46).

Women with insomnia had a 2.24-fold greater risk for MI than other women, whereas men with insomnia had a 2.03-fold greater risk for MI than other men.

Patients with insomnia had a greater risk for MI than those without insomnia in subgroups based on patients’ age (< 65 and > 65), follow up duration (≤ 5 years and > 5 years), and comorbidities (diabetes, hypertension, and hyperlipidemia).

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Insomnia – difficulty falling or staying asleep – was associated with a 69% greater risk of having a myocardial infarction than among adults without insomnia, according to new research.

Those who slept 5 or fewer hours per night had the highest risk for MI, and those with both diabetes and insomnia had double the risk for MI, compared with patients without these comorbidities.

insomnia_senior_man_web.jpg

The findings are from a meta-analysis of studies in more than 1 million patients, almost all without prior MI who were, on average, in their early 50s and followed for 9 years.

Yomna E. Dean, a medical student at Alexandria (Egypt) University, reported these results in a press briefing, and the study was simultaneously published in Clinical Cardiology. It will be presented at the upcoming at the annual scientific sessions of the American College of Cardiology.

“Insomnia and ]at least] 5 hours of sleep are highly associated with increased incidence of MI, an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines,” the researchers concluded.

“We believe that [insomnia] should be screened and patients should be educated about the importance of sleep because nowadays insomnia is no longer a disease – sleep deprivation could also be a life choice,” Ms, Dean told a press conference prior to the meeting.

“Clinicians must educate the patients about the importance of sleep in maintaining a healthy heart and encourage proper sleep hygiene,” Ms. Dean reiterated in an email. “And if a patient still has insomnia, other methods should be considered such as cognitive-behavior[al] therapy for insomnia [CBT-I].”
 

Adds to growing evidence

This study does not allow any conclusion about whether treating insomnia will reduce heart attack risk, Jennifer L. Martin, PhD, president of the American Academy of Sleep Medicine, noted in a comment. Nor does it report the diversity of study participants, since insomnia is also a health equity issue, she noted, and insomnia symptoms and comorbidities were self-reported.

However, this analysis “adds to the growing evidence that poor quality or insufficient sleep is associated with poor health,” said Dr. Martin, professor of medicine at the University of California, Los Angeles, who was not involved with this research.

The study reinforces the recommendation from the American Heart Association, which includes “Get Healthy Sleep” as one of “Life’s Essential 8” for heart health, Dr. Martin noted.

“Particularly in primary care where disease prevention and health promotion are important, clinicians should be asking all patients about their sleep – just like they ask about diet and exercise – as a key aspect of maintaining heart health,” she said.

Advice about basic sleep hygiene advice is a first step, she noted.

When improved sleep hygiene is not enough to address chronic insomnia, the AASM’s clinical practice guidelines and the guidelines of the Department of Veterans Affairs/Department of Defense, recommend first-line treatment with CBT-I, typically offered by a sleep specialist or mental health clinician.

Similarly, the American College of Physicians suggests that sleeping pills should be reserved for short-term use in patients who may not benefit sufficiently from CBT-I.
 

Sleeping too little, too much, equally harmful

“Studies have found that insomnia and subsequent sleep deprivation puts the body under stress,” Ms. Dean said. “This triggers cortisol release which could accelerate atherosclerosis,” and increase risk of MI.

For this analysis, the researchers identified nine observational studies, published from 1998 to 2019, with data on incident MI in adults who had insomnia.

The diagnosis of insomnia was based on ICD diagnostic codes or on the DSM‐5, which defines insomnia as the presence of any of the following three symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep. Patients with sleep apnea were excluded.

The studies were in populations in China, Germany, Norway, Taiwan, United Kingdom, and United States, in 1.1 million adults aged 18 and older. The patients had a mean age of 52 years and 13% had insomnia.

During follow-up, 2,406 of 153,881 patients with insomnia, and 12,398 of 1,030,375 patients without insomnia had an MI.

In the pooled analysis, patients with insomnia had a significantly increased risk of MI (relative risk, 1.69; P < .00001), after adjusting for age, gender, diabetes, hypertension, high cholesterol, and smoking.

Sleeping 5 hours or less was associated with a greater risk for MI than sleeping 6 hours, or 7-8 hours, but sleeping 9 hours or more was just as harmful.

162409_graphic_web.png

Patients who had difficulty initiating and maintaining sleep – two symptoms of insomnia – had a 13% increased risk for MI compared with other patients (RR, 1.13; P = .003).

However, patients who had nonrestorative sleep and daytime dysfunction despite adequate sleep – which is common – did not have an increased risk of MI, compared with other patients (RR, 1.06; P = .46).

Women with insomnia had a 2.24-fold greater risk for MI than other women, whereas men with insomnia had a 2.03-fold greater risk for MI than other men.

Patients with insomnia had a greater risk for MI than those without insomnia in subgroups based on patients’ age (< 65 and > 65), follow up duration (≤ 5 years and > 5 years), and comorbidities (diabetes, hypertension, and hyperlipidemia).

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Insomnia – difficulty falling or staying asleep – was associated with a 69% greater risk of having a myocardial infarction than among adults without insomnia, according to new research.

Those who slept 5 or fewer hours per night had the highest risk for MI, and those with both diabetes and insomnia had double the risk for MI, compared with patients without these comorbidities.

insomnia_senior_man_web.jpg

The findings are from a meta-analysis of studies in more than 1 million patients, almost all without prior MI who were, on average, in their early 50s and followed for 9 years.

Yomna E. Dean, a medical student at Alexandria (Egypt) University, reported these results in a press briefing, and the study was simultaneously published in Clinical Cardiology. It will be presented at the upcoming at the annual scientific sessions of the American College of Cardiology.

“Insomnia and ]at least] 5 hours of sleep are highly associated with increased incidence of MI, an association comparable to that of other MI risk factors and as such, it should be considered as a risk factor for MI and to be incorporated into MI prevention guidelines,” the researchers concluded.

“We believe that [insomnia] should be screened and patients should be educated about the importance of sleep because nowadays insomnia is no longer a disease – sleep deprivation could also be a life choice,” Ms, Dean told a press conference prior to the meeting.

“Clinicians must educate the patients about the importance of sleep in maintaining a healthy heart and encourage proper sleep hygiene,” Ms. Dean reiterated in an email. “And if a patient still has insomnia, other methods should be considered such as cognitive-behavior[al] therapy for insomnia [CBT-I].”
 

Adds to growing evidence

This study does not allow any conclusion about whether treating insomnia will reduce heart attack risk, Jennifer L. Martin, PhD, president of the American Academy of Sleep Medicine, noted in a comment. Nor does it report the diversity of study participants, since insomnia is also a health equity issue, she noted, and insomnia symptoms and comorbidities were self-reported.

However, this analysis “adds to the growing evidence that poor quality or insufficient sleep is associated with poor health,” said Dr. Martin, professor of medicine at the University of California, Los Angeles, who was not involved with this research.

The study reinforces the recommendation from the American Heart Association, which includes “Get Healthy Sleep” as one of “Life’s Essential 8” for heart health, Dr. Martin noted.

“Particularly in primary care where disease prevention and health promotion are important, clinicians should be asking all patients about their sleep – just like they ask about diet and exercise – as a key aspect of maintaining heart health,” she said.

Advice about basic sleep hygiene advice is a first step, she noted.

When improved sleep hygiene is not enough to address chronic insomnia, the AASM’s clinical practice guidelines and the guidelines of the Department of Veterans Affairs/Department of Defense, recommend first-line treatment with CBT-I, typically offered by a sleep specialist or mental health clinician.

Similarly, the American College of Physicians suggests that sleeping pills should be reserved for short-term use in patients who may not benefit sufficiently from CBT-I.
 

Sleeping too little, too much, equally harmful

“Studies have found that insomnia and subsequent sleep deprivation puts the body under stress,” Ms. Dean said. “This triggers cortisol release which could accelerate atherosclerosis,” and increase risk of MI.

For this analysis, the researchers identified nine observational studies, published from 1998 to 2019, with data on incident MI in adults who had insomnia.

The diagnosis of insomnia was based on ICD diagnostic codes or on the DSM‐5, which defines insomnia as the presence of any of the following three symptoms: difficulty initiating sleep, difficulty maintaining sleep, or early morning awakening with inability to return to sleep. Patients with sleep apnea were excluded.

The studies were in populations in China, Germany, Norway, Taiwan, United Kingdom, and United States, in 1.1 million adults aged 18 and older. The patients had a mean age of 52 years and 13% had insomnia.

During follow-up, 2,406 of 153,881 patients with insomnia, and 12,398 of 1,030,375 patients without insomnia had an MI.

In the pooled analysis, patients with insomnia had a significantly increased risk of MI (relative risk, 1.69; P < .00001), after adjusting for age, gender, diabetes, hypertension, high cholesterol, and smoking.

Sleeping 5 hours or less was associated with a greater risk for MI than sleeping 6 hours, or 7-8 hours, but sleeping 9 hours or more was just as harmful.

162409_graphic_web.png

Patients who had difficulty initiating and maintaining sleep – two symptoms of insomnia – had a 13% increased risk for MI compared with other patients (RR, 1.13; P = .003).

However, patients who had nonrestorative sleep and daytime dysfunction despite adequate sleep – which is common – did not have an increased risk of MI, compared with other patients (RR, 1.06; P = .46).

Women with insomnia had a 2.24-fold greater risk for MI than other women, whereas men with insomnia had a 2.03-fold greater risk for MI than other men.

Patients with insomnia had a greater risk for MI than those without insomnia in subgroups based on patients’ age (< 65 and > 65), follow up duration (≤ 5 years and > 5 years), and comorbidities (diabetes, hypertension, and hyperlipidemia).

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter U.K. study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.

“We know that multiorgan involvement in hospitalized patients with COVID-19 is common ... and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations,” John P. Greenwood, PhD, of the University of Leeds (England), told this news organization. “Elevated cardiac troponin is associated with a worse prognosis.”

“Multiple mechanisms of myocardial injury have been proposed and ... mitigation or prevention strategies likely depend on the underpinning mechanisms,” he said. “The sequelae of scar may predispose to late events.”

The study, published online  in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Dr. Greenwood said.
 

Injury patterns different

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an “urgent public health study” in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19: before vaccination and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.

Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).

Overall, participants’ median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality – for example, left or right ventricular impairment, scar, or pericardial disease – was twice as great (61%) in COVID+/troponin+ cases, compared with controls (36% for COVID+/troponin− patients versus 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs. 3.1% and 7.1%) or scar (42% vs. 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs. 2% and 7%) or microinfarction (9% vs. 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs. 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases, compared with 1.7% in controls without COVID-19 – “much lower” than in previous studies, Dr. Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died, and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

“These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors,” the authors conclude.

Dr. Greenwood added, “We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity.”
 

‘Tour de force’

James A. de Lemos, MD, co-chair of the American Heart Association’s COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said, “This is a tour de force collaboration – obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies, [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury.”

Overall, he said, the findings “do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities.”

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne, Switzerland, noted in a related editorial, “We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved,” they noted.

“In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers,” they conclude.

No commercial funding or relevant financial relationships were reported.

A version of this article originally appeared on Medscape.com.

Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter U.K. study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.

“We know that multiorgan involvement in hospitalized patients with COVID-19 is common ... and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations,” John P. Greenwood, PhD, of the University of Leeds (England), told this news organization. “Elevated cardiac troponin is associated with a worse prognosis.”

“Multiple mechanisms of myocardial injury have been proposed and ... mitigation or prevention strategies likely depend on the underpinning mechanisms,” he said. “The sequelae of scar may predispose to late events.”

The study, published online  in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Dr. Greenwood said.
 

Injury patterns different

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an “urgent public health study” in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19: before vaccination and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.

Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).

Overall, participants’ median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality – for example, left or right ventricular impairment, scar, or pericardial disease – was twice as great (61%) in COVID+/troponin+ cases, compared with controls (36% for COVID+/troponin− patients versus 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs. 3.1% and 7.1%) or scar (42% vs. 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs. 2% and 7%) or microinfarction (9% vs. 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs. 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases, compared with 1.7% in controls without COVID-19 – “much lower” than in previous studies, Dr. Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died, and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

“These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors,” the authors conclude.

Dr. Greenwood added, “We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity.”
 

‘Tour de force’

James A. de Lemos, MD, co-chair of the American Heart Association’s COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said, “This is a tour de force collaboration – obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies, [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury.”

Overall, he said, the findings “do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities.”

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne, Switzerland, noted in a related editorial, “We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved,” they noted.

“In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers,” they conclude.

No commercial funding or relevant financial relationships were reported.

A version of this article originally appeared on Medscape.com.

Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter U.K. study suggests.

The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.

“We know that multiorgan involvement in hospitalized patients with COVID-19 is common ... and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations,” John P. Greenwood, PhD, of the University of Leeds (England), told this news organization. “Elevated cardiac troponin is associated with a worse prognosis.”

“Multiple mechanisms of myocardial injury have been proposed and ... mitigation or prevention strategies likely depend on the underpinning mechanisms,” he said. “The sequelae of scar may predispose to late events.”

The study, published online  in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Dr. Greenwood said.
 

Injury patterns different

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an “urgent public health study” in the United Kingdom. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19: before vaccination and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.

Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).

Overall, participants’ median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).

The frequency of any heart abnormality – for example, left or right ventricular impairment, scar, or pericardial disease – was twice as great (61%) in COVID+/troponin+ cases, compared with controls (36% for COVID+/troponin− patients versus 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs. 3.1% and 7.1%) or scar (42% vs. 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs. 2% and 7%) or microinfarction (9% vs. 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs. 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases, compared with 1.7% in controls without COVID-19 – “much lower” than in previous studies, Dr. Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died, and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

“These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors,” the authors conclude.

Dr. Greenwood added, “We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires, and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity.”
 

‘Tour de force’

James A. de Lemos, MD, co-chair of the American Heart Association’s COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center, Dallas, said, “This is a tour de force collaboration – obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies, [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury.”

Overall, he said, the findings “do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities.”

Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne, Switzerland, noted in a related editorial, “We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved,” they noted.

“In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers,” they conclude.

No commercial funding or relevant financial relationships were reported.

A version of this article originally appeared on Medscape.com.

A new study provides more evidence that endocarditis associated with drug use is a significant and growing health concern, and further demonstrates that this risk has been exacerbated by the COVID-19 pandemic.

The rate of infective endocarditis among individuals in the United States with opioid or cocaine use disorder increased in the 11-year period 2011 to 2022, with the steepest increase logged during the COVID-19 pandemic (2021-2022), according to the study.

A diagnosis of COVID-19 more than doubled the risk for a new diagnosis of endocarditis in patients with either cocaine (hazard ratio, 2.24) or opioid use disorder (HR, 2.23).

“Our data suggests that, in addition to the major social disruption from the pandemic, including disrupted access to health care, COVID-19 infection itself is a significant risk factor for new diagnosis of endocarditis in drug using populations,” authors Nora Volkow, MD, director of the National Institute on Drug Abuse, and colleagues wrote.

“Drug-using populations, particularly those who use cocaine or opioids, have some of the highest risk for endocarditis, and here we show that having a COVID-19 diagnoses further increases this risk,” they added.

The study was published online in Molecular Psychiatry.

The researchers analyzed electronic health record data collected from January 2011 to August 2022 for more than 109 million people across the United States, including more than 736,000 with an opioid use disorder and more than 379,000 with a cocaine use disorder.

In 2011, there were 4 cases of endocarditis per day for every 1 million people with opioid use disorder. By 2022, the rate had increased to 30 cases per day per 1 million people with opioid use disorder.

For people with cocaine use disorder, cases of endocarditis increased from 5 per 1 million in 2011 to 23 per 1 million in 2022.

Among individuals with cocaine or opioid use disorder, the risk of being hospitalized within 180 days following a diagnosis of endocarditis was higher in those with than without COVID-19 (67.5% vs. 58.7%; HR, 1.21). 

The risk of dying within 180 days following new diagnosis of endocarditis was also higher in those with than without COVID-19 (9.2% vs. 8%; HR, 1.16).

The study also showed that Black and Hispanic individuals had a lower risk for COVID-19-associated endocarditis than non-Hispanic White individuals, which is consistent with a higher prevalence of injection drug use in non-Hispanic White populations, compared with Black or Hispanic populations, the researchers pointed out.

Dr. Volkow and colleagues said their findings highlight the need to screen drug users for endocarditis and link them to infectious disease and addiction treatment if they contract COVID-19.

“People with substance use disorder already face major impediments to proper health care due to lack of access and stigma,” Dr. Volkow said in a news release. 

“Proven techniques like syringe service programs, which help people avoid infection from reused or shared injection equipment, can help prevent this often fatal and costly condition,” Dr. Volkow added.

The authors said it will also be important to determine exactly how SARS-CoV-2 viral infection exacerbates the risk for endocarditis in drug users.

Support for the study was provided by the National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute Case Comprehensive Cancer Center. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study provides more evidence that endocarditis associated with drug use is a significant and growing health concern, and further demonstrates that this risk has been exacerbated by the COVID-19 pandemic.

The rate of infective endocarditis among individuals in the United States with opioid or cocaine use disorder increased in the 11-year period 2011 to 2022, with the steepest increase logged during the COVID-19 pandemic (2021-2022), according to the study.

A diagnosis of COVID-19 more than doubled the risk for a new diagnosis of endocarditis in patients with either cocaine (hazard ratio, 2.24) or opioid use disorder (HR, 2.23).

“Our data suggests that, in addition to the major social disruption from the pandemic, including disrupted access to health care, COVID-19 infection itself is a significant risk factor for new diagnosis of endocarditis in drug using populations,” authors Nora Volkow, MD, director of the National Institute on Drug Abuse, and colleagues wrote.

“Drug-using populations, particularly those who use cocaine or opioids, have some of the highest risk for endocarditis, and here we show that having a COVID-19 diagnoses further increases this risk,” they added.

The study was published online in Molecular Psychiatry.

The researchers analyzed electronic health record data collected from January 2011 to August 2022 for more than 109 million people across the United States, including more than 736,000 with an opioid use disorder and more than 379,000 with a cocaine use disorder.

In 2011, there were 4 cases of endocarditis per day for every 1 million people with opioid use disorder. By 2022, the rate had increased to 30 cases per day per 1 million people with opioid use disorder.

For people with cocaine use disorder, cases of endocarditis increased from 5 per 1 million in 2011 to 23 per 1 million in 2022.

Among individuals with cocaine or opioid use disorder, the risk of being hospitalized within 180 days following a diagnosis of endocarditis was higher in those with than without COVID-19 (67.5% vs. 58.7%; HR, 1.21). 

The risk of dying within 180 days following new diagnosis of endocarditis was also higher in those with than without COVID-19 (9.2% vs. 8%; HR, 1.16).

The study also showed that Black and Hispanic individuals had a lower risk for COVID-19-associated endocarditis than non-Hispanic White individuals, which is consistent with a higher prevalence of injection drug use in non-Hispanic White populations, compared with Black or Hispanic populations, the researchers pointed out.

Dr. Volkow and colleagues said their findings highlight the need to screen drug users for endocarditis and link them to infectious disease and addiction treatment if they contract COVID-19.

“People with substance use disorder already face major impediments to proper health care due to lack of access and stigma,” Dr. Volkow said in a news release. 

“Proven techniques like syringe service programs, which help people avoid infection from reused or shared injection equipment, can help prevent this often fatal and costly condition,” Dr. Volkow added.

The authors said it will also be important to determine exactly how SARS-CoV-2 viral infection exacerbates the risk for endocarditis in drug users.

Support for the study was provided by the National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute Case Comprehensive Cancer Center. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study provides more evidence that endocarditis associated with drug use is a significant and growing health concern, and further demonstrates that this risk has been exacerbated by the COVID-19 pandemic.

The rate of infective endocarditis among individuals in the United States with opioid or cocaine use disorder increased in the 11-year period 2011 to 2022, with the steepest increase logged during the COVID-19 pandemic (2021-2022), according to the study.

A diagnosis of COVID-19 more than doubled the risk for a new diagnosis of endocarditis in patients with either cocaine (hazard ratio, 2.24) or opioid use disorder (HR, 2.23).

“Our data suggests that, in addition to the major social disruption from the pandemic, including disrupted access to health care, COVID-19 infection itself is a significant risk factor for new diagnosis of endocarditis in drug using populations,” authors Nora Volkow, MD, director of the National Institute on Drug Abuse, and colleagues wrote.

“Drug-using populations, particularly those who use cocaine or opioids, have some of the highest risk for endocarditis, and here we show that having a COVID-19 diagnoses further increases this risk,” they added.

The study was published online in Molecular Psychiatry.

The researchers analyzed electronic health record data collected from January 2011 to August 2022 for more than 109 million people across the United States, including more than 736,000 with an opioid use disorder and more than 379,000 with a cocaine use disorder.

In 2011, there were 4 cases of endocarditis per day for every 1 million people with opioid use disorder. By 2022, the rate had increased to 30 cases per day per 1 million people with opioid use disorder.

For people with cocaine use disorder, cases of endocarditis increased from 5 per 1 million in 2011 to 23 per 1 million in 2022.

Among individuals with cocaine or opioid use disorder, the risk of being hospitalized within 180 days following a diagnosis of endocarditis was higher in those with than without COVID-19 (67.5% vs. 58.7%; HR, 1.21). 

The risk of dying within 180 days following new diagnosis of endocarditis was also higher in those with than without COVID-19 (9.2% vs. 8%; HR, 1.16).

The study also showed that Black and Hispanic individuals had a lower risk for COVID-19-associated endocarditis than non-Hispanic White individuals, which is consistent with a higher prevalence of injection drug use in non-Hispanic White populations, compared with Black or Hispanic populations, the researchers pointed out.

Dr. Volkow and colleagues said their findings highlight the need to screen drug users for endocarditis and link them to infectious disease and addiction treatment if they contract COVID-19.

“People with substance use disorder already face major impediments to proper health care due to lack of access and stigma,” Dr. Volkow said in a news release. 

“Proven techniques like syringe service programs, which help people avoid infection from reused or shared injection equipment, can help prevent this often fatal and costly condition,” Dr. Volkow added.

The authors said it will also be important to determine exactly how SARS-CoV-2 viral infection exacerbates the risk for endocarditis in drug users.

Support for the study was provided by the National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, the Clinical and Translational Science Collaborative of Cleveland, and the National Cancer Institute Case Comprehensive Cancer Center. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.

The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.

Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.

The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).

The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.

In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.

Eight cases occurred after the second vaccine dose. All nine cases were mild.

Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.

Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.

Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.

Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.

At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.

This research had no specific funding. Five authors have received research grants from Pfizer.

A version of this article first appeared on Medscape.com.

New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.

The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.

Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.

The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).

The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.

In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.

Eight cases occurred after the second vaccine dose. All nine cases were mild.

Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.

Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.

Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.

Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.

At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.

This research had no specific funding. Five authors have received research grants from Pfizer.

A version of this article first appeared on Medscape.com.

New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.

The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.

Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.

The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).

The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.

In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.

Eight cases occurred after the second vaccine dose. All nine cases were mild.

Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.

Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.

Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.

Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.

At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.

This research had no specific funding. Five authors have received research grants from Pfizer.

A version of this article first appeared on Medscape.com.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

drug_pills_web.jpg

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

drug_pills_web.jpg

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

drug_pills_web.jpg

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.