Cardiology

Preexisting statin use may help protect hospitalized patients with COVID-19 against negative outcomes, including death, a large retrospective analysis suggests.

Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.

They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.

“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”

He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.

In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.

To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.

The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.

Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).

A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.

“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”

Prospective studies needed before practice changes

How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.

“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”

Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.

Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”

Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.

“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.

The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.

Preexisting statin use may help protect hospitalized patients with COVID-19 against negative outcomes, including death, a large retrospective analysis suggests.

Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.

They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.

“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”

He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.

In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.

To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.

The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.

Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).

A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.

“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”

Prospective studies needed before practice changes

How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.

“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”

Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.

Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”

Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.

“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.

The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.

Preexisting statin use may help protect hospitalized patients with COVID-19 against negative outcomes, including death, a large retrospective analysis suggests.

Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.

They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.

“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”

He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.

In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.

To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.

The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.

Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).

A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.

“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”

Prospective studies needed before practice changes

How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.

“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”

Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.

Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”

Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.

“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.

The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.

Both male and female internal medicine (IM) residents prioritized work-life balance, such as stable working hours and family friendliness, when considering career choices, and cardiology was perceived to fall short in this area, an updated survey revealed.

Originally conducted in 2010, the survey aimed to understand IM residents’ professional development preferences and perceptions of cardiology as a specialty. That survey demonstrated a discordance between what residents valued in making a career choice and their perceptions of a career in cardiology.

The discordance remained in 2020, with residents even more likely than their predecessors to report negative perceptions of cardiology.

Compared with residents surveyed in 2010, respondents in 2020 placed higher value on all aspects of work-life balance and of having role models who demonstrated a successful balance. The value change was particularly notable for men.

“While our survey does not elucidate why this is, speculation could be made that this value on work-life balance is generational and prominent in the youngest generations entering all professional fields, not just medicine,” lead author Meghan York, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, told this news organization.

“There is also an interesting trend that dual-career couples are on the rise in the U.S.,” she said. “This may reflect that trend, [with] men in medical fields possibly taking on more domestic responsibility and requiring more work flexibility to do that.”

Regarding perceptions, she added, cardiology tends to show resident cardiologists who are working in inpatient services with “ballooning and unpredictable hours,” rather than those who are working in more time-controlled clinics. Therefore, “their prime exposure to physicians is not truly representative of the career.” The study was published online in JAMA Cardiology.
 

‘Lack of diversity’

The updated surveys were sent by various means to close to 30,000 residents, and were completed by 840 (mean age, 29; 50% male; 55% White). Cardiology was a favored subspecialty choice among men, with 46.5% reporting they were considering it vs. 29.7% of women. Women were more likely to report never having considered cardiology as a career choice (37.6%) compared with men (22.3%).

The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions.

The most important professional development preferences for respondents were positive role models (4.56), stimulating career (3.81), family friendly (3.78), patient focus (3.70), stable work hours (3.66), female or race friendly (3.33), professional challenges (3.21), and financial benefits (3.20).

The cardiology perception statements with the highest agreement were:

• Interferes with family life during training (3.93).
• Having met positive role models or having positive views of cardiovascular disease as a topic (3.85).
• Reasonable compensation (3.69).
• Adverse job conditions (3.16).
• Field lacks diversity (2.90).

Compared with the 2010 survey, the 2020 findings indicated increased importance on work-life balance components for both male and female residents, with a greater change among males.

In addition, 2020 respondents were more likely than their predecessors to report negative perceptions of cardiology, such as too much overnight or weekend call, challenging to have children during fellowship, and lack of diversity.

“The culture of the subspecialty of cardiology has not improved to become significantly more diverse or inclusive, whereas other specialties and subspecialties have, and residents interact with cardiologists frequently and can see that,” Dr. York noted.

“As women now make up greater than 50% of medical students,” she said, “it is reasonable to focus on women in medical school and residency to bring them into the field of cardiology. But as racial and ethnic minority groups are also massively underrepresented in medical school, recruitment into medicine needs to start much earlier, in high school and college.

“Creating and supporting rotations that embed residents in the outpatient cardiology setting and exposure to more longitudinal experiences will provide a more realistic picture of the career,” she concluded. 
 

ACC ‘at the forefront’

“Work-life balance looks different for each and every individual, but there are some themes that we need to think about,” Lisa Rose-Jones, MD, chair of the American College of Cardiology’s Program Directors and Graduate Medical Educators Section, said in her comments on the study. “The ACC is really at the forefront of this. They are putting together different work groups to focus on ‘how can we have some innovations?’ ”

The ACC is seeking mentors as part of its workforce diversity efforts among African American/Black, Hispanic/LatinX and Women’s IM cardiology programs, she noted. Furthermore, on Oct. 13, the organization released its 2022 health policy statement on career flexibility in cardiology, which calls for more leeway for cardiologists to deal with common life events without jeopardizing their careers.  

Dr. Rose-Jones, director of the training program in cardiovascular disease at the University of North Carolina at Chapel Hill, said that because both male and female residents placed a high value on work-life balance, “we’ve got to think about how we can have flexibility in our work hours. That is critically important. Health systems need to be able to accommodate working families that may need to alter traditional 9 to 5 work hours to meet the demands of being a successful cardiologist and also being a parent.”

In addition, she said, “We need to have very clear policies at every institution on gender-related and parent-related discrimination. Data show that many female trainees are still being questioned on their family planning. That is absolutely not appropriate. It is none of our business. While we continue to do that, we continue to create stigma in our field.”

Like Dr. York, she noted generational differences in the doctors who are coming up now. “They’ve seen burnout firsthand and want to have a well-balanced life that includes medicine, but also life outside of the hospital,” Dr. Rose-Jones said. “So, those of us in cardiology really need to look deep inside and make changes. We need to be thoughtful about how we can be innovative.”

No commercial funding or conflicts of interest were declared.

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

Both male and female internal medicine (IM) residents prioritized work-life balance, such as stable working hours and family friendliness, when considering career choices, and cardiology was perceived to fall short in this area, an updated survey revealed.

Originally conducted in 2010, the survey aimed to understand IM residents’ professional development preferences and perceptions of cardiology as a specialty. That survey demonstrated a discordance between what residents valued in making a career choice and their perceptions of a career in cardiology.

The discordance remained in 2020, with residents even more likely than their predecessors to report negative perceptions of cardiology.

Compared with residents surveyed in 2010, respondents in 2020 placed higher value on all aspects of work-life balance and of having role models who demonstrated a successful balance. The value change was particularly notable for men.

“While our survey does not elucidate why this is, speculation could be made that this value on work-life balance is generational and prominent in the youngest generations entering all professional fields, not just medicine,” lead author Meghan York, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, told this news organization.

“There is also an interesting trend that dual-career couples are on the rise in the U.S.,” she said. “This may reflect that trend, [with] men in medical fields possibly taking on more domestic responsibility and requiring more work flexibility to do that.”

Regarding perceptions, she added, cardiology tends to show resident cardiologists who are working in inpatient services with “ballooning and unpredictable hours,” rather than those who are working in more time-controlled clinics. Therefore, “their prime exposure to physicians is not truly representative of the career.” The study was published online in JAMA Cardiology.
 

‘Lack of diversity’

The updated surveys were sent by various means to close to 30,000 residents, and were completed by 840 (mean age, 29; 50% male; 55% White). Cardiology was a favored subspecialty choice among men, with 46.5% reporting they were considering it vs. 29.7% of women. Women were more likely to report never having considered cardiology as a career choice (37.6%) compared with men (22.3%).

The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions.

The most important professional development preferences for respondents were positive role models (4.56), stimulating career (3.81), family friendly (3.78), patient focus (3.70), stable work hours (3.66), female or race friendly (3.33), professional challenges (3.21), and financial benefits (3.20).

The cardiology perception statements with the highest agreement were:

• Interferes with family life during training (3.93).
• Having met positive role models or having positive views of cardiovascular disease as a topic (3.85).
• Reasonable compensation (3.69).
• Adverse job conditions (3.16).
• Field lacks diversity (2.90).

Compared with the 2010 survey, the 2020 findings indicated increased importance on work-life balance components for both male and female residents, with a greater change among males.

In addition, 2020 respondents were more likely than their predecessors to report negative perceptions of cardiology, such as too much overnight or weekend call, challenging to have children during fellowship, and lack of diversity.

“The culture of the subspecialty of cardiology has not improved to become significantly more diverse or inclusive, whereas other specialties and subspecialties have, and residents interact with cardiologists frequently and can see that,” Dr. York noted.

“As women now make up greater than 50% of medical students,” she said, “it is reasonable to focus on women in medical school and residency to bring them into the field of cardiology. But as racial and ethnic minority groups are also massively underrepresented in medical school, recruitment into medicine needs to start much earlier, in high school and college.

“Creating and supporting rotations that embed residents in the outpatient cardiology setting and exposure to more longitudinal experiences will provide a more realistic picture of the career,” she concluded. 
 

ACC ‘at the forefront’

“Work-life balance looks different for each and every individual, but there are some themes that we need to think about,” Lisa Rose-Jones, MD, chair of the American College of Cardiology’s Program Directors and Graduate Medical Educators Section, said in her comments on the study. “The ACC is really at the forefront of this. They are putting together different work groups to focus on ‘how can we have some innovations?’ ”

The ACC is seeking mentors as part of its workforce diversity efforts among African American/Black, Hispanic/LatinX and Women’s IM cardiology programs, she noted. Furthermore, on Oct. 13, the organization released its 2022 health policy statement on career flexibility in cardiology, which calls for more leeway for cardiologists to deal with common life events without jeopardizing their careers.  

Dr. Rose-Jones, director of the training program in cardiovascular disease at the University of North Carolina at Chapel Hill, said that because both male and female residents placed a high value on work-life balance, “we’ve got to think about how we can have flexibility in our work hours. That is critically important. Health systems need to be able to accommodate working families that may need to alter traditional 9 to 5 work hours to meet the demands of being a successful cardiologist and also being a parent.”

In addition, she said, “We need to have very clear policies at every institution on gender-related and parent-related discrimination. Data show that many female trainees are still being questioned on their family planning. That is absolutely not appropriate. It is none of our business. While we continue to do that, we continue to create stigma in our field.”

Like Dr. York, she noted generational differences in the doctors who are coming up now. “They’ve seen burnout firsthand and want to have a well-balanced life that includes medicine, but also life outside of the hospital,” Dr. Rose-Jones said. “So, those of us in cardiology really need to look deep inside and make changes. We need to be thoughtful about how we can be innovative.”

No commercial funding or conflicts of interest were declared.

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

Both male and female internal medicine (IM) residents prioritized work-life balance, such as stable working hours and family friendliness, when considering career choices, and cardiology was perceived to fall short in this area, an updated survey revealed.

Originally conducted in 2010, the survey aimed to understand IM residents’ professional development preferences and perceptions of cardiology as a specialty. That survey demonstrated a discordance between what residents valued in making a career choice and their perceptions of a career in cardiology.

The discordance remained in 2020, with residents even more likely than their predecessors to report negative perceptions of cardiology.

Compared with residents surveyed in 2010, respondents in 2020 placed higher value on all aspects of work-life balance and of having role models who demonstrated a successful balance. The value change was particularly notable for men.

“While our survey does not elucidate why this is, speculation could be made that this value on work-life balance is generational and prominent in the youngest generations entering all professional fields, not just medicine,” lead author Meghan York, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, told this news organization.

“There is also an interesting trend that dual-career couples are on the rise in the U.S.,” she said. “This may reflect that trend, [with] men in medical fields possibly taking on more domestic responsibility and requiring more work flexibility to do that.”

Regarding perceptions, she added, cardiology tends to show resident cardiologists who are working in inpatient services with “ballooning and unpredictable hours,” rather than those who are working in more time-controlled clinics. Therefore, “their prime exposure to physicians is not truly representative of the career.” The study was published online in JAMA Cardiology.
 

‘Lack of diversity’

The updated surveys were sent by various means to close to 30,000 residents, and were completed by 840 (mean age, 29; 50% male; 55% White). Cardiology was a favored subspecialty choice among men, with 46.5% reporting they were considering it vs. 29.7% of women. Women were more likely to report never having considered cardiology as a career choice (37.6%) compared with men (22.3%).

The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions.

The most important professional development preferences for respondents were positive role models (4.56), stimulating career (3.81), family friendly (3.78), patient focus (3.70), stable work hours (3.66), female or race friendly (3.33), professional challenges (3.21), and financial benefits (3.20).

The cardiology perception statements with the highest agreement were:

• Interferes with family life during training (3.93).
• Having met positive role models or having positive views of cardiovascular disease as a topic (3.85).
• Reasonable compensation (3.69).
• Adverse job conditions (3.16).
• Field lacks diversity (2.90).

Compared with the 2010 survey, the 2020 findings indicated increased importance on work-life balance components for both male and female residents, with a greater change among males.

In addition, 2020 respondents were more likely than their predecessors to report negative perceptions of cardiology, such as too much overnight or weekend call, challenging to have children during fellowship, and lack of diversity.

“The culture of the subspecialty of cardiology has not improved to become significantly more diverse or inclusive, whereas other specialties and subspecialties have, and residents interact with cardiologists frequently and can see that,” Dr. York noted.

“As women now make up greater than 50% of medical students,” she said, “it is reasonable to focus on women in medical school and residency to bring them into the field of cardiology. But as racial and ethnic minority groups are also massively underrepresented in medical school, recruitment into medicine needs to start much earlier, in high school and college.

“Creating and supporting rotations that embed residents in the outpatient cardiology setting and exposure to more longitudinal experiences will provide a more realistic picture of the career,” she concluded. 
 

ACC ‘at the forefront’

“Work-life balance looks different for each and every individual, but there are some themes that we need to think about,” Lisa Rose-Jones, MD, chair of the American College of Cardiology’s Program Directors and Graduate Medical Educators Section, said in her comments on the study. “The ACC is really at the forefront of this. They are putting together different work groups to focus on ‘how can we have some innovations?’ ”

The ACC is seeking mentors as part of its workforce diversity efforts among African American/Black, Hispanic/LatinX and Women’s IM cardiology programs, she noted. Furthermore, on Oct. 13, the organization released its 2022 health policy statement on career flexibility in cardiology, which calls for more leeway for cardiologists to deal with common life events without jeopardizing their careers.  

Dr. Rose-Jones, director of the training program in cardiovascular disease at the University of North Carolina at Chapel Hill, said that because both male and female residents placed a high value on work-life balance, “we’ve got to think about how we can have flexibility in our work hours. That is critically important. Health systems need to be able to accommodate working families that may need to alter traditional 9 to 5 work hours to meet the demands of being a successful cardiologist and also being a parent.”

In addition, she said, “We need to have very clear policies at every institution on gender-related and parent-related discrimination. Data show that many female trainees are still being questioned on their family planning. That is absolutely not appropriate. It is none of our business. While we continue to do that, we continue to create stigma in our field.”

Like Dr. York, she noted generational differences in the doctors who are coming up now. “They’ve seen burnout firsthand and want to have a well-balanced life that includes medicine, but also life outside of the hospital,” Dr. Rose-Jones said. “So, those of us in cardiology really need to look deep inside and make changes. We need to be thoughtful about how we can be innovative.”

No commercial funding or conflicts of interest were declared.

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

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.

Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).

However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.

Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.

“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.

Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.

In the study population, 180 patients were identified as low risk and 289 were considered high risk.

Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.

A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.

Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.

Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.

The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.

“We are likely overusing chemical VTE prophylaxis in low-risk patients,” he concluded.

Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Apixaban offers greater protection than rivaroxaban against ischemic stroke, systemic embolism, and bleeding in patients with both atrial fibrillation (AFib) and valvular heart disease (VHD), a new study finds.

Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.

In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.

The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.

“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.

Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
 

Study results

Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).

Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.

The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.

“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
 

Head-to-head trial needed to change practice

Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”

Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.

“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”

Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.

The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.

Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.

“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.

On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.

More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.

This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.

Apixaban offers greater protection than rivaroxaban against ischemic stroke, systemic embolism, and bleeding in patients with both atrial fibrillation (AFib) and valvular heart disease (VHD), a new study finds.

Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.

In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.

The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.

“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.

Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
 

Study results

Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).

Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.

The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.

“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
 

Head-to-head trial needed to change practice

Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”

Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.

“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”

Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.

The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.

Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.

“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.

On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.

More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.

This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.

Apixaban offers greater protection than rivaroxaban against ischemic stroke, systemic embolism, and bleeding in patients with both atrial fibrillation (AFib) and valvular heart disease (VHD), a new study finds.

Compared with rivaroxaban, apixaban cut risks nearly in half, suggesting that clinicians should consider these new data when choosing an anticoagulant, reported lead author Ghadeer K. Dawwas, PhD, of the University of Pennsylvania, Philadelphia, and colleagues.

In the new retrospective study involving almost 20,000 patients, Dr. Dawwas and her colleagues “emulated a target trial” using private insurance claims from Optum’s deidentified Clinformatics Data Mart Database. The cohort was narrowed from a screened population of 58,210 patients with concurrent AFib and VHD to 9,947 new apixaban users who could be closely matched with 9,947 new rivaroxaban users. Covariates included provider specialty, type of VHD, demographic characteristics, measures of health care use, baseline use of medications, and baseline comorbidities.

The primary effectiveness outcome was a composite of systemic embolism and ischemic stroke, while the primary safety outcome was a composite of intracranial or gastrointestinal bleeding.

“Although several ongoing trials aim to compare apixaban with warfarin in patients with AFib and VHD, none of these trials will directly compare apixaban and rivaroxaban,” the investigators wrote. Their report is in Annals of Internal Medicine.

Dr. Dawwas and colleagues previously showed that direct oral anticoagulants (DOACs) were safer and more effective than warfarin in the same patient population. Comparing apixaban and rivaroxaban – the two most common DOACs – was the next logical step, Dr. Dawwas said in an interview.
 

Study results

Compared with rivaroxaban, patients who received apixaban had a 43% reduced risk of stroke or embolism (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.40-0.80). Apixaban’s ability to protect against bleeding appeared even more pronounced, with a 49% reduced risk over rivaroxaban (HR, 0.51; 95% CI, 0.41-0.62).

Comparing the two agents on an absolute basis, apixaban reduced risk of embolism or stroke by 0.2% within the first 6 months of treatment initiation, and 1.1% within the first year of initiation. At the same time points, absolute risk reductions for bleeding were 1.2% and 1.9%, respectively.

The investigators noted that their results held consistent in an alternative analysis that considered separate types of VHD.

“Based on the results from our analysis, we showed that apixaban is effective and safe in patients with atrial fibrillation and valvular heart diseases,” Dr. Dawwas said.
 

Head-to-head trial needed to change practice

Christopher M. Bianco, DO, associate professor of medicine at West Virginia University Heart and Vascular Institute, Morgantown, said the findings “add to the growing body of literature,” but “a head-to-head trial would be necessary to make a definitive change to clinical practice.”

Dr. Bianco, who recently conducted a retrospective analysis of apixaban and rivaroxaban that found no difference in safety and efficacy among a different patient population, said these kinds of studies are helpful in generating hypotheses, but they can’t account for all relevant clinical factors.

“There are just so many things that go into the decision-making process of [prescribing] apixaban and rivaroxaban,” he said. “Even though [Dr. Dawwas and colleagues] used propensity matching, you’re never going to be able to sort that out with a retrospective analysis.”

Specifically, Dr. Bianco noted that the findings did not include dose data. This is a key gap, he said, considering how often real-world datasets have shown that providers underdose DOACs for a number of unaccountable reasons, and how frequently patients exhibit poor adherence.

The study also lacked detail concerning the degree of renal dysfunction, which can determine drug eligibility, Dr. Bianco said. Furthermore, attempts to stratify patients based on thrombosis and bleeding risk were likely “insufficient,” he added.

Dr. Bianco also cautioned that the investigators defined valvular heart disease as any valve-related disease of any severity. In contrast, previous studies have generally restricted valvular heart disease to patients with mitral stenosis or prosthetic valves.

“This is definitely not the traditional definition of valvular heart disease, so the title is a little bit misleading in that sense, although they certainly do disclose that in the methods,” Dr. Bianco said.

On a more positive note, he highlighted the size of the patient population, and the real-world data, which included many patients who would be excluded from clinical trials.

More broadly, the study helps drive research forward, Dr. Bianco concluded; namely, by attracting financial support for a more powerful head-to-head trial that drug makers are unlikely to fund due to inherent market risk.

This study was supported by the National Institutes of Health. The investigators disclosed additional relationships with Takeda, Spark, Sanofi, and others. Dr. Bianco disclosed no conflicts of interest.

People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.

The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.

Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.

“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
 

Early consequences

To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.

Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.

Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).

The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).

Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.

About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.

Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.

The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.

Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.

“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
 

Possible missed cases

As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.

“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.

Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.

While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.

Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.

Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.

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

People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.

The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.

Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.

“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
 

Early consequences

To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.

Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.

Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).

The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).

Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.

About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.

Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.

The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.

Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.

“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
 

Possible missed cases

As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.

“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.

Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.

While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.

Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.

Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.

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

People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.

The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.

Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.

“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
 

Early consequences

To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.

Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.

Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).

The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).

Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.

About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.

Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.

The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.

Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.

“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
 

Possible missed cases

As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.

“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.

Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.

While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.

Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.

Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.

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

Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.

The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.

Mitchel L. Zoler/MDedge news

Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m^{2 despite also having albuminuria with a UACR of at least 30 mg/g}, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.

“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.

The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.

The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.

Mitchel L. Zoler/MDedge News

A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
 

A new reason to screen for albuminuria

“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.

Mitchel L. Zoler/MDedge News

“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.

The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m² in FIDELIO-DKD, and as high as 90 mL/min/1.73m² in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.

In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.

The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m². The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
 

Finerenone favors patients with less advanced CKD

In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”

Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.

Mitchel L. Zoler/MDedge news

“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.

The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”

The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.

The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.

Mitchel L. Zoler/MDedge news

Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m^{2 despite also having albuminuria with a UACR of at least 30 mg/g}, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.

“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.

The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.

The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.

Mitchel L. Zoler/MDedge News

A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
 

A new reason to screen for albuminuria

“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.

Mitchel L. Zoler/MDedge News

“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.

The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m² in FIDELIO-DKD, and as high as 90 mL/min/1.73m² in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.

In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.

The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m². The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
 

Finerenone favors patients with less advanced CKD

In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”

Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.

Mitchel L. Zoler/MDedge news

“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.

The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”

The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.

The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.

Mitchel L. Zoler/MDedge news

Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m^{2 despite also having albuminuria with a UACR of at least 30 mg/g}, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.

“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.

The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.

The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.

Mitchel L. Zoler/MDedge News

A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
 

A new reason to screen for albuminuria

“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.

Mitchel L. Zoler/MDedge News

“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.

The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m² in FIDELIO-DKD, and as high as 90 mL/min/1.73m² in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.

In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.

The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m². The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
 

Finerenone favors patients with less advanced CKD

In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”

Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.

Mitchel L. Zoler/MDedge news

“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.

The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”

The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.

ANAHEIM – A wide range of factors can cause myocarditis; most often viral infections cause myocarditis in children and teens, according to Ryan Butts, MD, medical director of the pediatric advanced cardiac care program at the University of Texas Southwestern Medical Center and Children’s Health of Texas.

Dr. Butts provided an overview of what pediatricians and other clinicians caring for children and teens should know about myocarditis at the annual meeting of the American Academy of Pediatrics.

The important new things that attendees may want to take away from this for their practice are improved recognition and diagnostic workup for acute viral myocarditis, making sure cardiology follow-up occurs after an admission for the condition, enhanced evaluation of the child before they return to competitive sports, and the availability of written or verbal education for patients relating to COVID vaccine–associated myocarditis, Dr. Butts said.

He also provided a set of key takeaways:

• Myocarditis is rare.
• The most common viruses causing myocarditis are always changing.
• Myocarditis is most common in infants and teenagers but it has different clinical patterns in each population.
• MRI is becoming the diagnostic tool of choice.
• IVIG frequently is used but good evidence for the therapy is lacking.
• Patients may go home on cardiac medications but have good long-term outcomes.
• Patients must have a 6-month restriction on competitive sports after diagnosis.

Frank Han, MD, a pediatric cardiologist at OSF Medical Center and Children’s Hospital of Illinois in Peoria, said he found the most helpful parts of Dr. Butts’ presentation to be the diagnosis and triage of myocarditis in the major age groups.

“Myocarditis can have variable presentations, and its cause may influence how the myocarditis behaves,” Dr. Han said. Pediatric cardiologists, he said, are uniquely positioned to triage and diagnose myocarditis.
 

Epidemiology and presentation

Just 0.05% of admissions from 28.6 million U.S. pediatric ED visits every year are for myocarditis, Dr. Butts said. While viruses are the most common cause of myocarditis, bacterial infections and noninfectious causes, including hypersensitivity reactions, systemic disorders, and toxic substances, can also cause the condition. The dominant viruses causing myocarditis have shifted over the years as well. Coxsackie B was the most common cause in the 1980s, but adenovirus became more common in the 1990s and parvovirus B19 in the 2000s. Why some kids develop myocarditis while others don’t is unclear, but the host-immune response to the virus likely plays an important role.

Research has shown two substantial spikes in the incidence of myocarditis children: infants under 2 years old and teens aged 14-19. Although myocarditis refers to any inflammation of myocardium not caused by ischemia, the signs, symptoms, and lab results vary according to patient’s age group. The only constant is that diaphoresis is rare across all ages.

Infants are more likely to show respiratory distress (68%) and an enlarged liver (40%) but can also present with gastrointestinal symptoms (24%). Vomiting without fever or diarrhea should arouse clinical suspicion of myocarditis in infants, although fever and diarrhea can occur.

In young children, who have the lowest incidence, fatigue presents in about one-third, with 20% presenting with chest pain and 20% with hepatomegaly. The most common symptom in teens by far (80%) is chest pain. About one-third also have respiratory distress but gastrointestinal symptoms are less common (20%).

When should a clinician suspect myocarditis in a teen presenting with chest pain? “If the chest pain is reproducible and if you can localize it, they don’t need further evaluation,” Dr. Butts said. “After that, it’s a lot about the history.”

In terms of lab results, ventricular function measured by brain natriuretic peptide is significantly depressed in infants and young children but often near normal in teens. Inflammatory markers (C-reactive protein) tend to be low in infants but elevated in young children and teens. And troponin levels, denoting myocardial injury, are minimal in infants and young children but elevated in teens. Median ejection fraction on echocardiograms, about 55% in normal hearts, will often be low in infants and young children, around 30%-33%, but is near normal (54%) in teens.
 

Diagnosis and management

Cardiac MRI increasingly has been replacing endomyocardial biopsy for diagnosis, with MRI exceeding biopsy use between 2009 and 2010, Dr. Butts said. The advantage of endomyocardial biopsy is that it’s specific, if not very sensitive. The test is invasive, however, requiring sedation and carrying the risk of tricuspid injury. The most common finding on cardiac MRI is late gadolinium enhancement (80%) while early gadolinium enhancement is less common (55%).

Although Dr. Butts mentioned the Dallas diagnostic criteria from 1987, he advocated for the more recent Lake Louise Criteria, which require clinical suspicion of myocarditis and at least two of three findings on MRI: T2-weighted myocardial abnormalities, T1 early or late gadolinium enhancement, or regional wall motion abnormalities or evidence of pericarditis

Point-of-care ultrasound can be useful for detecting myocarditis, but its success depends on whether the user can pick up on the subtle changes in ventricular function. “Just because someone has a point-of-care ultrasound that’s normal or thought to be normal, it shouldn’t rule out the diagnosis,” he said.

Learning the etiology of viral myocarditis often is difficult, and etiology doesn’t affect management of the condition, Dr. Butts said. Even in cases of myocarditis confirmed by biopsy, the virus may be identified in only about 60%-70% of cases with myocardial polymerase chain reaction. In clinical cases, the virus can be determined only about 25%-30% of the time with serum PCR.

Prognosis is usually good, with 80%-90% of children and teens going home transplant free despite most arriving critically ill and 50%-80% initially being admitted to ICU. Two-thirds of those discharged go home with heart failure medications, but only one in six are readmitted within a year.

The strongest risk factors for poor prognosis are younger age and being critically ill at presentation but other risk factors include female sex, poor ventricular function, poor perfusion on exam, increased dilation on echocardiogram, and a need for ECMO or inotropes or mechanical ventilation.

That said, Dr. Butts cautioned attendees not to ignore normal function. In one study of 171 patients, among 75 who presented with normal function, 15% went home with inotropes, 12% required mechanical ventilation, 9% had arrhythmia, and 5% needed extracorporeal membrane oxygenation.

A big question in treatment is whether to give IVIG or not and the evidence is murky, Dr. Butts said. He reviewed a couple studies on IVIG, including one that suggested better ventricular functional recovery with the treatment but those who received IVIG were also more likely to be on an ACE inhibitor.

“Was it the ACE inhibitor or was it IVIG? We don’t know,” he said. Different cardiologists may give different opinions on IVIG. “It has nothing to do with the actual evidence behind it.”

IVIG has drawbacks: It’s very expensive and it involves risks that include serum sickness and interstitial nephritis.

“Pediatricians typically aren’t going to directly decide on giving or not giving IVIG,” Dr. Han said. “Typically, the ultimate choice comes from a group discussion between the hospital cardiologist – perhaps the hospitalist pediatrician if they are involved – and the family. We acknowledge the ambiguity of the evidence and decide based upon the severity of the initial disease process.”
 

Return to competitive sports; Follow-up critical

Experts are much more confident, however, about when teens admitted with viral myocarditis can return to competitive sports. But Dr. Butts said he suspects the guidelines for these children aren’t followed as closely as they should be. The American Heart Association recommends waiting 6 months after discharge and ensuring the athlete has a normal echocardiogram, Holter monitoring, and stress test.

“It’s incredibly important to have them come back and see the cardiologist 6 months after admission,” Dr. Butts said. “The only patient I’ve ever had who died 6-7 months post myocarditis is somebody who, during their stress test, had increasing ventricular ectopy. I told him not to do sports. He didn’t listen to me and unfortunately passed away – I’m assuming from arrhythmia.”
 

COVID and vaccine-associated myocarditis

Vaccine-associated myocarditis is substantially milder than viral myocarditis, Dr. Butts said. A small study from a single center in Atlanta found that ejection fraction at admission was normal, around 56%, in those with vaccine-associated myocarditis, compared with 45% with non-COVID viral myocarditis and 50% with multisystem inflammatory syndrome in children or myocarditis from COVID-19. All patients with vaccine-associated myocarditis had normal function at discharge, compared with 73% of those with viral myocarditis and 93% with COVID-associated myocarditis.

While 22% of those with vaccine-associated myocarditis were admitted to the ICU, twice as many (40%) with viral myocarditis were, and three times as many (68%) with COVID-associated myocarditis ended up in intensive care.

Dr. Butts also noted a Morbidity and Mortality Weekly Report from the Centers of Disease Control and Prevention that found teen boys had two to six times greater risk of heart complications after COVID-19 infection than after COVID vaccination.

In terms of direct comparisons, vaccine-related myocarditis occurred about 12-18 times per 100,000 doses for boys ages 5-11 years, compared with cardiac involvement in 93-133 cases out of 100,000 COVID-19 infections. Boys aged 12-17 years experienced 12-21 cases of myocarditis per 100,000 doses of the vaccine, compared with cardiac involvement in 50-64 out of 100,000 infections.

The bottom line, Dr. Butts said, is that cardiac involvement in MIS-C is common, but typically improves by discharge. “Vaccine-associated myocarditis is a mild clinical syndrome that has a very short duration, and, in my opinion, should never lead us to ever advise anybody not to get the vaccine. I’ve had many patients, even patients in their first year post transplant, who have gotten the COVID-19 vaccine and were just fine.”

Dr. Butts acknowledged that talking with families about the risk of myocarditis with the vaccine is challenging. He often starts these conversations by sharing the statistics, but he said relatable stories are the key. He will also relate the statistics to something the parents and teen will understand, whether it’s sports or another comparison. He does recommend that teens who develop vaccine-associated myocarditis complete the series and get the booster. Their chances of developing myocarditis again are extremely low, whereas “the likelihood of them being really ill from COVID-19 is much, much higher.”

Dr. Butts and Dr. Han had no disclosures. The presentation involved no external funding.

ANAHEIM – A wide range of factors can cause myocarditis; most often viral infections cause myocarditis in children and teens, according to Ryan Butts, MD, medical director of the pediatric advanced cardiac care program at the University of Texas Southwestern Medical Center and Children’s Health of Texas.

Dr. Butts provided an overview of what pediatricians and other clinicians caring for children and teens should know about myocarditis at the annual meeting of the American Academy of Pediatrics.

The important new things that attendees may want to take away from this for their practice are improved recognition and diagnostic workup for acute viral myocarditis, making sure cardiology follow-up occurs after an admission for the condition, enhanced evaluation of the child before they return to competitive sports, and the availability of written or verbal education for patients relating to COVID vaccine–associated myocarditis, Dr. Butts said.

He also provided a set of key takeaways:

• Myocarditis is rare.
• The most common viruses causing myocarditis are always changing.
• Myocarditis is most common in infants and teenagers but it has different clinical patterns in each population.
• MRI is becoming the diagnostic tool of choice.
• IVIG frequently is used but good evidence for the therapy is lacking.
• Patients may go home on cardiac medications but have good long-term outcomes.
• Patients must have a 6-month restriction on competitive sports after diagnosis.

Frank Han, MD, a pediatric cardiologist at OSF Medical Center and Children’s Hospital of Illinois in Peoria, said he found the most helpful parts of Dr. Butts’ presentation to be the diagnosis and triage of myocarditis in the major age groups.

“Myocarditis can have variable presentations, and its cause may influence how the myocarditis behaves,” Dr. Han said. Pediatric cardiologists, he said, are uniquely positioned to triage and diagnose myocarditis.
 

Epidemiology and presentation

Just 0.05% of admissions from 28.6 million U.S. pediatric ED visits every year are for myocarditis, Dr. Butts said. While viruses are the most common cause of myocarditis, bacterial infections and noninfectious causes, including hypersensitivity reactions, systemic disorders, and toxic substances, can also cause the condition. The dominant viruses causing myocarditis have shifted over the years as well. Coxsackie B was the most common cause in the 1980s, but adenovirus became more common in the 1990s and parvovirus B19 in the 2000s. Why some kids develop myocarditis while others don’t is unclear, but the host-immune response to the virus likely plays an important role.

Research has shown two substantial spikes in the incidence of myocarditis children: infants under 2 years old and teens aged 14-19. Although myocarditis refers to any inflammation of myocardium not caused by ischemia, the signs, symptoms, and lab results vary according to patient’s age group. The only constant is that diaphoresis is rare across all ages.

Infants are more likely to show respiratory distress (68%) and an enlarged liver (40%) but can also present with gastrointestinal symptoms (24%). Vomiting without fever or diarrhea should arouse clinical suspicion of myocarditis in infants, although fever and diarrhea can occur.

In young children, who have the lowest incidence, fatigue presents in about one-third, with 20% presenting with chest pain and 20% with hepatomegaly. The most common symptom in teens by far (80%) is chest pain. About one-third also have respiratory distress but gastrointestinal symptoms are less common (20%).

When should a clinician suspect myocarditis in a teen presenting with chest pain? “If the chest pain is reproducible and if you can localize it, they don’t need further evaluation,” Dr. Butts said. “After that, it’s a lot about the history.”

In terms of lab results, ventricular function measured by brain natriuretic peptide is significantly depressed in infants and young children but often near normal in teens. Inflammatory markers (C-reactive protein) tend to be low in infants but elevated in young children and teens. And troponin levels, denoting myocardial injury, are minimal in infants and young children but elevated in teens. Median ejection fraction on echocardiograms, about 55% in normal hearts, will often be low in infants and young children, around 30%-33%, but is near normal (54%) in teens.
 

Diagnosis and management

Cardiac MRI increasingly has been replacing endomyocardial biopsy for diagnosis, with MRI exceeding biopsy use between 2009 and 2010, Dr. Butts said. The advantage of endomyocardial biopsy is that it’s specific, if not very sensitive. The test is invasive, however, requiring sedation and carrying the risk of tricuspid injury. The most common finding on cardiac MRI is late gadolinium enhancement (80%) while early gadolinium enhancement is less common (55%).

Although Dr. Butts mentioned the Dallas diagnostic criteria from 1987, he advocated for the more recent Lake Louise Criteria, which require clinical suspicion of myocarditis and at least two of three findings on MRI: T2-weighted myocardial abnormalities, T1 early or late gadolinium enhancement, or regional wall motion abnormalities or evidence of pericarditis

Point-of-care ultrasound can be useful for detecting myocarditis, but its success depends on whether the user can pick up on the subtle changes in ventricular function. “Just because someone has a point-of-care ultrasound that’s normal or thought to be normal, it shouldn’t rule out the diagnosis,” he said.

Learning the etiology of viral myocarditis often is difficult, and etiology doesn’t affect management of the condition, Dr. Butts said. Even in cases of myocarditis confirmed by biopsy, the virus may be identified in only about 60%-70% of cases with myocardial polymerase chain reaction. In clinical cases, the virus can be determined only about 25%-30% of the time with serum PCR.

Prognosis is usually good, with 80%-90% of children and teens going home transplant free despite most arriving critically ill and 50%-80% initially being admitted to ICU. Two-thirds of those discharged go home with heart failure medications, but only one in six are readmitted within a year.

The strongest risk factors for poor prognosis are younger age and being critically ill at presentation but other risk factors include female sex, poor ventricular function, poor perfusion on exam, increased dilation on echocardiogram, and a need for ECMO or inotropes or mechanical ventilation.

That said, Dr. Butts cautioned attendees not to ignore normal function. In one study of 171 patients, among 75 who presented with normal function, 15% went home with inotropes, 12% required mechanical ventilation, 9% had arrhythmia, and 5% needed extracorporeal membrane oxygenation.

A big question in treatment is whether to give IVIG or not and the evidence is murky, Dr. Butts said. He reviewed a couple studies on IVIG, including one that suggested better ventricular functional recovery with the treatment but those who received IVIG were also more likely to be on an ACE inhibitor.

“Was it the ACE inhibitor or was it IVIG? We don’t know,” he said. Different cardiologists may give different opinions on IVIG. “It has nothing to do with the actual evidence behind it.”

IVIG has drawbacks: It’s very expensive and it involves risks that include serum sickness and interstitial nephritis.

“Pediatricians typically aren’t going to directly decide on giving or not giving IVIG,” Dr. Han said. “Typically, the ultimate choice comes from a group discussion between the hospital cardiologist – perhaps the hospitalist pediatrician if they are involved – and the family. We acknowledge the ambiguity of the evidence and decide based upon the severity of the initial disease process.”
 

Return to competitive sports; Follow-up critical

Experts are much more confident, however, about when teens admitted with viral myocarditis can return to competitive sports. But Dr. Butts said he suspects the guidelines for these children aren’t followed as closely as they should be. The American Heart Association recommends waiting 6 months after discharge and ensuring the athlete has a normal echocardiogram, Holter monitoring, and stress test.

“It’s incredibly important to have them come back and see the cardiologist 6 months after admission,” Dr. Butts said. “The only patient I’ve ever had who died 6-7 months post myocarditis is somebody who, during their stress test, had increasing ventricular ectopy. I told him not to do sports. He didn’t listen to me and unfortunately passed away – I’m assuming from arrhythmia.”
 

COVID and vaccine-associated myocarditis

Vaccine-associated myocarditis is substantially milder than viral myocarditis, Dr. Butts said. A small study from a single center in Atlanta found that ejection fraction at admission was normal, around 56%, in those with vaccine-associated myocarditis, compared with 45% with non-COVID viral myocarditis and 50% with multisystem inflammatory syndrome in children or myocarditis from COVID-19. All patients with vaccine-associated myocarditis had normal function at discharge, compared with 73% of those with viral myocarditis and 93% with COVID-associated myocarditis.

While 22% of those with vaccine-associated myocarditis were admitted to the ICU, twice as many (40%) with viral myocarditis were, and three times as many (68%) with COVID-associated myocarditis ended up in intensive care.

Dr. Butts also noted a Morbidity and Mortality Weekly Report from the Centers of Disease Control and Prevention that found teen boys had two to six times greater risk of heart complications after COVID-19 infection than after COVID vaccination.

In terms of direct comparisons, vaccine-related myocarditis occurred about 12-18 times per 100,000 doses for boys ages 5-11 years, compared with cardiac involvement in 93-133 cases out of 100,000 COVID-19 infections. Boys aged 12-17 years experienced 12-21 cases of myocarditis per 100,000 doses of the vaccine, compared with cardiac involvement in 50-64 out of 100,000 infections.

The bottom line, Dr. Butts said, is that cardiac involvement in MIS-C is common, but typically improves by discharge. “Vaccine-associated myocarditis is a mild clinical syndrome that has a very short duration, and, in my opinion, should never lead us to ever advise anybody not to get the vaccine. I’ve had many patients, even patients in their first year post transplant, who have gotten the COVID-19 vaccine and were just fine.”

Dr. Butts acknowledged that talking with families about the risk of myocarditis with the vaccine is challenging. He often starts these conversations by sharing the statistics, but he said relatable stories are the key. He will also relate the statistics to something the parents and teen will understand, whether it’s sports or another comparison. He does recommend that teens who develop vaccine-associated myocarditis complete the series and get the booster. Their chances of developing myocarditis again are extremely low, whereas “the likelihood of them being really ill from COVID-19 is much, much higher.”

Dr. Butts and Dr. Han had no disclosures. The presentation involved no external funding.

ANAHEIM – A wide range of factors can cause myocarditis; most often viral infections cause myocarditis in children and teens, according to Ryan Butts, MD, medical director of the pediatric advanced cardiac care program at the University of Texas Southwestern Medical Center and Children’s Health of Texas.

Dr. Butts provided an overview of what pediatricians and other clinicians caring for children and teens should know about myocarditis at the annual meeting of the American Academy of Pediatrics.

The important new things that attendees may want to take away from this for their practice are improved recognition and diagnostic workup for acute viral myocarditis, making sure cardiology follow-up occurs after an admission for the condition, enhanced evaluation of the child before they return to competitive sports, and the availability of written or verbal education for patients relating to COVID vaccine–associated myocarditis, Dr. Butts said.

He also provided a set of key takeaways:

• Myocarditis is rare.
• The most common viruses causing myocarditis are always changing.
• Myocarditis is most common in infants and teenagers but it has different clinical patterns in each population.
• MRI is becoming the diagnostic tool of choice.
• IVIG frequently is used but good evidence for the therapy is lacking.
• Patients may go home on cardiac medications but have good long-term outcomes.
• Patients must have a 6-month restriction on competitive sports after diagnosis.

Frank Han, MD, a pediatric cardiologist at OSF Medical Center and Children’s Hospital of Illinois in Peoria, said he found the most helpful parts of Dr. Butts’ presentation to be the diagnosis and triage of myocarditis in the major age groups.

“Myocarditis can have variable presentations, and its cause may influence how the myocarditis behaves,” Dr. Han said. Pediatric cardiologists, he said, are uniquely positioned to triage and diagnose myocarditis.
 

Epidemiology and presentation

Just 0.05% of admissions from 28.6 million U.S. pediatric ED visits every year are for myocarditis, Dr. Butts said. While viruses are the most common cause of myocarditis, bacterial infections and noninfectious causes, including hypersensitivity reactions, systemic disorders, and toxic substances, can also cause the condition. The dominant viruses causing myocarditis have shifted over the years as well. Coxsackie B was the most common cause in the 1980s, but adenovirus became more common in the 1990s and parvovirus B19 in the 2000s. Why some kids develop myocarditis while others don’t is unclear, but the host-immune response to the virus likely plays an important role.

Research has shown two substantial spikes in the incidence of myocarditis children: infants under 2 years old and teens aged 14-19. Although myocarditis refers to any inflammation of myocardium not caused by ischemia, the signs, symptoms, and lab results vary according to patient’s age group. The only constant is that diaphoresis is rare across all ages.

Infants are more likely to show respiratory distress (68%) and an enlarged liver (40%) but can also present with gastrointestinal symptoms (24%). Vomiting without fever or diarrhea should arouse clinical suspicion of myocarditis in infants, although fever and diarrhea can occur.

In young children, who have the lowest incidence, fatigue presents in about one-third, with 20% presenting with chest pain and 20% with hepatomegaly. The most common symptom in teens by far (80%) is chest pain. About one-third also have respiratory distress but gastrointestinal symptoms are less common (20%).

When should a clinician suspect myocarditis in a teen presenting with chest pain? “If the chest pain is reproducible and if you can localize it, they don’t need further evaluation,” Dr. Butts said. “After that, it’s a lot about the history.”

In terms of lab results, ventricular function measured by brain natriuretic peptide is significantly depressed in infants and young children but often near normal in teens. Inflammatory markers (C-reactive protein) tend to be low in infants but elevated in young children and teens. And troponin levels, denoting myocardial injury, are minimal in infants and young children but elevated in teens. Median ejection fraction on echocardiograms, about 55% in normal hearts, will often be low in infants and young children, around 30%-33%, but is near normal (54%) in teens.
 

Diagnosis and management

Cardiac MRI increasingly has been replacing endomyocardial biopsy for diagnosis, with MRI exceeding biopsy use between 2009 and 2010, Dr. Butts said. The advantage of endomyocardial biopsy is that it’s specific, if not very sensitive. The test is invasive, however, requiring sedation and carrying the risk of tricuspid injury. The most common finding on cardiac MRI is late gadolinium enhancement (80%) while early gadolinium enhancement is less common (55%).

Although Dr. Butts mentioned the Dallas diagnostic criteria from 1987, he advocated for the more recent Lake Louise Criteria, which require clinical suspicion of myocarditis and at least two of three findings on MRI: T2-weighted myocardial abnormalities, T1 early or late gadolinium enhancement, or regional wall motion abnormalities or evidence of pericarditis

Point-of-care ultrasound can be useful for detecting myocarditis, but its success depends on whether the user can pick up on the subtle changes in ventricular function. “Just because someone has a point-of-care ultrasound that’s normal or thought to be normal, it shouldn’t rule out the diagnosis,” he said.

Learning the etiology of viral myocarditis often is difficult, and etiology doesn’t affect management of the condition, Dr. Butts said. Even in cases of myocarditis confirmed by biopsy, the virus may be identified in only about 60%-70% of cases with myocardial polymerase chain reaction. In clinical cases, the virus can be determined only about 25%-30% of the time with serum PCR.

Prognosis is usually good, with 80%-90% of children and teens going home transplant free despite most arriving critically ill and 50%-80% initially being admitted to ICU. Two-thirds of those discharged go home with heart failure medications, but only one in six are readmitted within a year.

The strongest risk factors for poor prognosis are younger age and being critically ill at presentation but other risk factors include female sex, poor ventricular function, poor perfusion on exam, increased dilation on echocardiogram, and a need for ECMO or inotropes or mechanical ventilation.

That said, Dr. Butts cautioned attendees not to ignore normal function. In one study of 171 patients, among 75 who presented with normal function, 15% went home with inotropes, 12% required mechanical ventilation, 9% had arrhythmia, and 5% needed extracorporeal membrane oxygenation.

A big question in treatment is whether to give IVIG or not and the evidence is murky, Dr. Butts said. He reviewed a couple studies on IVIG, including one that suggested better ventricular functional recovery with the treatment but those who received IVIG were also more likely to be on an ACE inhibitor.

“Was it the ACE inhibitor or was it IVIG? We don’t know,” he said. Different cardiologists may give different opinions on IVIG. “It has nothing to do with the actual evidence behind it.”

IVIG has drawbacks: It’s very expensive and it involves risks that include serum sickness and interstitial nephritis.

“Pediatricians typically aren’t going to directly decide on giving or not giving IVIG,” Dr. Han said. “Typically, the ultimate choice comes from a group discussion between the hospital cardiologist – perhaps the hospitalist pediatrician if they are involved – and the family. We acknowledge the ambiguity of the evidence and decide based upon the severity of the initial disease process.”
 

Return to competitive sports; Follow-up critical

Experts are much more confident, however, about when teens admitted with viral myocarditis can return to competitive sports. But Dr. Butts said he suspects the guidelines for these children aren’t followed as closely as they should be. The American Heart Association recommends waiting 6 months after discharge and ensuring the athlete has a normal echocardiogram, Holter monitoring, and stress test.

“It’s incredibly important to have them come back and see the cardiologist 6 months after admission,” Dr. Butts said. “The only patient I’ve ever had who died 6-7 months post myocarditis is somebody who, during their stress test, had increasing ventricular ectopy. I told him not to do sports. He didn’t listen to me and unfortunately passed away – I’m assuming from arrhythmia.”
 

COVID and vaccine-associated myocarditis

Vaccine-associated myocarditis is substantially milder than viral myocarditis, Dr. Butts said. A small study from a single center in Atlanta found that ejection fraction at admission was normal, around 56%, in those with vaccine-associated myocarditis, compared with 45% with non-COVID viral myocarditis and 50% with multisystem inflammatory syndrome in children or myocarditis from COVID-19. All patients with vaccine-associated myocarditis had normal function at discharge, compared with 73% of those with viral myocarditis and 93% with COVID-associated myocarditis.

While 22% of those with vaccine-associated myocarditis were admitted to the ICU, twice as many (40%) with viral myocarditis were, and three times as many (68%) with COVID-associated myocarditis ended up in intensive care.

Dr. Butts also noted a Morbidity and Mortality Weekly Report from the Centers of Disease Control and Prevention that found teen boys had two to six times greater risk of heart complications after COVID-19 infection than after COVID vaccination.

In terms of direct comparisons, vaccine-related myocarditis occurred about 12-18 times per 100,000 doses for boys ages 5-11 years, compared with cardiac involvement in 93-133 cases out of 100,000 COVID-19 infections. Boys aged 12-17 years experienced 12-21 cases of myocarditis per 100,000 doses of the vaccine, compared with cardiac involvement in 50-64 out of 100,000 infections.

The bottom line, Dr. Butts said, is that cardiac involvement in MIS-C is common, but typically improves by discharge. “Vaccine-associated myocarditis is a mild clinical syndrome that has a very short duration, and, in my opinion, should never lead us to ever advise anybody not to get the vaccine. I’ve had many patients, even patients in their first year post transplant, who have gotten the COVID-19 vaccine and were just fine.”

Dr. Butts acknowledged that talking with families about the risk of myocarditis with the vaccine is challenging. He often starts these conversations by sharing the statistics, but he said relatable stories are the key. He will also relate the statistics to something the parents and teen will understand, whether it’s sports or another comparison. He does recommend that teens who develop vaccine-associated myocarditis complete the series and get the booster. Their chances of developing myocarditis again are extremely low, whereas “the likelihood of them being really ill from COVID-19 is much, much higher.”

Dr. Butts and Dr. Han had no disclosures. The presentation involved no external funding.

The ability of an Apple Watch to detect atrial fibrillation (AFib) is significantly affected by underlying ECG abnormalities such as sinus node dysfunction, atrioventricular (AV) block, or intraventricular conduction delay (IVCD), a single-center study suggests.

LDProd/Getty Images

“We were surprised to find that in one in every five patients, the smartwatch ECG failed to produce an automatic diagnosis,” study author Marc Strik, MD, PhD, a clinician at Bordeaux University Hospital in Pessac, France, told this news organization. “This [failure] was mostly due to insufficient quality of the tracing [60%], but in a third of cases, [34%], it was due to bradycardia, and in some cases, tachycardia [6%].

“We were also surprised to find that the existence of ventricular conduction disease was associated with a higher likelihood of missing AFib,” he said.

The study was published in the Canadian Journal of Cardiology.
 

Abnormalities affected detection

The investigators tested the accuracy of the Apple Watch (Apple, Cupertino, California) in detecting AFib in patients with various ECG anomalies. All participants underwent 12-lead ECG, followed by a 30-second ECG tracing with an Apple Watch Series 5. The smartwatch’s automated AFib detection algorithm gave a result of “no signs of AFib,” “AFib,” or “not checked for AFib (unclassified).”

Unclassified recordings resulted from “low heart rate” (below 50 beats/min), “high heart rate” (above 150 beats/min), “poor recording,” or “inconclusive recording.”

The smartwatch recordings were reviewed by a blinded electrophysiologist who interpreted each tracing and assigned a diagnosis of “AFib,” “absence of AFib,” or “diagnosis unclear.” To assess interobserver agreement, a second blinded electrophysiologist interpreted 100 randomly selected tracings.

Among the 734 patients (mean age, 66; 58% men) enrolled, 539 (73%) were in normal sinus rhythm (SR), 154 (21%) in AFib, 33 in atrial flutter or atrial tachycardia, 3 in ventricular tachycardia, and 5 in junctional tachycardia.

Furthermore, 65 (8.9%) had sinus node dysfunction, 21 (2.9%) had second- or third-degree AV block, 39 (5.3%) had a ventricular paced rhythm, 54 (7.4%) had premature ventricular contractions (PVCs), and 132 (18%) had IVCD (right or left bundle branch block or nonspecific IVCD).

Of the 539 patients in normal SR, 437 recordings were correctly diagnosed by the smartwatch, 7 were diagnosed incorrectly as AFib, and 95 were not classified.

Of the 187 patients in AFib, 129 were correctly diagnosed, 17 were incorrectly diagnosed as SR, and 41 were not classified.

When unclassified ECGs were considered false results, the smartwatch had a sensitivity of 69% and specificity of 81% for AFib detection. When unclassified ECGs were excluded from the analysis, sensitivity was 88%, and specificity was 98%.

Compared with patients without the abnormality, the relative risk of having false positive tracings was higher for patients with premature atrial contractions (PACs) or PVCs (risk ratio, 2.9), sinus node dysfunction (RR, 3.71), and AV block (RR, 7.8).

Fifty-eight patients with AFib were classified as SR or inconclusive by the smartwatch. Among them, 21 (36%) had an IVCD, 7 (12%) had a ventricular paced rhythm, and 5 (9%) had PACs or PVCs.

The risk of having false negative tracings (missed AF) was higher for patients with IVCD (RR, 2.6) and pacing (RR, 2.47), compared with those without the abnormality.
 

‘A powerful tool’

Overall, cardiac electrophysiologists showed high agreement in differentiating between AFib and non-AFib, with high interobserver reproducibility. A manual diagnosis was not possible for 10% of tracings because of either poor ECG quality (3%) or unclear P-waves (7%).

Fifty-nine of the 580 patients in SR were misclassified as AFib by the experts, and 5 of the 154 patients in AFib were misclassified as SR.

“Our results show that the presence of sinus node dysfunction, second- or third-degree AV block, ventricular paced rhythm, PVCs, and IVCD were more frequently represented in smartwatch misdiagnoses,” wrote the authors. “Patients with PVCs were three times as likely to have false positive AFib diagnoses.”

Study limitations included the single-center nature of the study and the fact that patients were recruited in a cardiology office. The latter factor may have influenced the incidence of ECG abnormalities, which was much higher than for the average smartwatch user.

“Even with its limitations, the smartwatch remains a powerful tool that is able to detect AFib and multiple other abnormalities,” said Dr. Strik. “Missed diagnosis of AFib may be less important in real life because of repeated measurements, and algorithms will continue to improve.”
 

Technology improving

Richard C. Becker, MD, director and physician in chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said, “This is exactly the kind of investigation required to improve upon existing detection algorithms that will someday facilitate routine use in patient care. An ability to detect AFib in a large proportion of those with the heart rhythm abnormality is encouraging.”

The findings should not detract from well-conducted studies in otherwise healthy individuals of varied age in whom AFib was accurately detected, he added. “Similarly, an automatic diagnosis algorithm for AF, pending optimization and validation in a large and diverse cohort, should be viewed as a communication tool between patients and health care providers.”

Patients at risk for developing AFib could benefit from continuous monitoring using a smartwatch, said Dr. Becker. “Pre-existing heart rhythm abnormalities must be taken into consideration. Optimal utilization of emerging technology to include wearables requires an understanding of performance and limitations. It is best undertaken in coordination with a health care provider.”

Andrés F. Miranda-Arboleda, MD, and Adrian Baranchuk, MD, of Kingston Health Sciences Center, Canada, conclude in an accompanying editorial, “In a certain manner, the smartwatch algorithms for the detection of AFib in patients with cardiovascular conditions are not yet smart enough ... but they may soon be.”

The study was supported by the French government. Dr. Strik, Dr. Miranda-Arboleda, Dr. Baranchuk, and Dr. Becker reported no conflicts of interest.

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

The ability of an Apple Watch to detect atrial fibrillation (AFib) is significantly affected by underlying ECG abnormalities such as sinus node dysfunction, atrioventricular (AV) block, or intraventricular conduction delay (IVCD), a single-center study suggests.

LDProd/Getty Images

“We were surprised to find that in one in every five patients, the smartwatch ECG failed to produce an automatic diagnosis,” study author Marc Strik, MD, PhD, a clinician at Bordeaux University Hospital in Pessac, France, told this news organization. “This [failure] was mostly due to insufficient quality of the tracing [60%], but in a third of cases, [34%], it was due to bradycardia, and in some cases, tachycardia [6%].

“We were also surprised to find that the existence of ventricular conduction disease was associated with a higher likelihood of missing AFib,” he said.

The study was published in the Canadian Journal of Cardiology.
 

Abnormalities affected detection

The investigators tested the accuracy of the Apple Watch (Apple, Cupertino, California) in detecting AFib in patients with various ECG anomalies. All participants underwent 12-lead ECG, followed by a 30-second ECG tracing with an Apple Watch Series 5. The smartwatch’s automated AFib detection algorithm gave a result of “no signs of AFib,” “AFib,” or “not checked for AFib (unclassified).”

Unclassified recordings resulted from “low heart rate” (below 50 beats/min), “high heart rate” (above 150 beats/min), “poor recording,” or “inconclusive recording.”

The smartwatch recordings were reviewed by a blinded electrophysiologist who interpreted each tracing and assigned a diagnosis of “AFib,” “absence of AFib,” or “diagnosis unclear.” To assess interobserver agreement, a second blinded electrophysiologist interpreted 100 randomly selected tracings.

Among the 734 patients (mean age, 66; 58% men) enrolled, 539 (73%) were in normal sinus rhythm (SR), 154 (21%) in AFib, 33 in atrial flutter or atrial tachycardia, 3 in ventricular tachycardia, and 5 in junctional tachycardia.

Furthermore, 65 (8.9%) had sinus node dysfunction, 21 (2.9%) had second- or third-degree AV block, 39 (5.3%) had a ventricular paced rhythm, 54 (7.4%) had premature ventricular contractions (PVCs), and 132 (18%) had IVCD (right or left bundle branch block or nonspecific IVCD).

Of the 539 patients in normal SR, 437 recordings were correctly diagnosed by the smartwatch, 7 were diagnosed incorrectly as AFib, and 95 were not classified.

Of the 187 patients in AFib, 129 were correctly diagnosed, 17 were incorrectly diagnosed as SR, and 41 were not classified.

When unclassified ECGs were considered false results, the smartwatch had a sensitivity of 69% and specificity of 81% for AFib detection. When unclassified ECGs were excluded from the analysis, sensitivity was 88%, and specificity was 98%.

Compared with patients without the abnormality, the relative risk of having false positive tracings was higher for patients with premature atrial contractions (PACs) or PVCs (risk ratio, 2.9), sinus node dysfunction (RR, 3.71), and AV block (RR, 7.8).

Fifty-eight patients with AFib were classified as SR or inconclusive by the smartwatch. Among them, 21 (36%) had an IVCD, 7 (12%) had a ventricular paced rhythm, and 5 (9%) had PACs or PVCs.

The risk of having false negative tracings (missed AF) was higher for patients with IVCD (RR, 2.6) and pacing (RR, 2.47), compared with those without the abnormality.
 

‘A powerful tool’

Overall, cardiac electrophysiologists showed high agreement in differentiating between AFib and non-AFib, with high interobserver reproducibility. A manual diagnosis was not possible for 10% of tracings because of either poor ECG quality (3%) or unclear P-waves (7%).

Fifty-nine of the 580 patients in SR were misclassified as AFib by the experts, and 5 of the 154 patients in AFib were misclassified as SR.

“Our results show that the presence of sinus node dysfunction, second- or third-degree AV block, ventricular paced rhythm, PVCs, and IVCD were more frequently represented in smartwatch misdiagnoses,” wrote the authors. “Patients with PVCs were three times as likely to have false positive AFib diagnoses.”

Study limitations included the single-center nature of the study and the fact that patients were recruited in a cardiology office. The latter factor may have influenced the incidence of ECG abnormalities, which was much higher than for the average smartwatch user.

“Even with its limitations, the smartwatch remains a powerful tool that is able to detect AFib and multiple other abnormalities,” said Dr. Strik. “Missed diagnosis of AFib may be less important in real life because of repeated measurements, and algorithms will continue to improve.”
 

Technology improving

Richard C. Becker, MD, director and physician in chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said, “This is exactly the kind of investigation required to improve upon existing detection algorithms that will someday facilitate routine use in patient care. An ability to detect AFib in a large proportion of those with the heart rhythm abnormality is encouraging.”

The findings should not detract from well-conducted studies in otherwise healthy individuals of varied age in whom AFib was accurately detected, he added. “Similarly, an automatic diagnosis algorithm for AF, pending optimization and validation in a large and diverse cohort, should be viewed as a communication tool between patients and health care providers.”

Patients at risk for developing AFib could benefit from continuous monitoring using a smartwatch, said Dr. Becker. “Pre-existing heart rhythm abnormalities must be taken into consideration. Optimal utilization of emerging technology to include wearables requires an understanding of performance and limitations. It is best undertaken in coordination with a health care provider.”

Andrés F. Miranda-Arboleda, MD, and Adrian Baranchuk, MD, of Kingston Health Sciences Center, Canada, conclude in an accompanying editorial, “In a certain manner, the smartwatch algorithms for the detection of AFib in patients with cardiovascular conditions are not yet smart enough ... but they may soon be.”

The study was supported by the French government. Dr. Strik, Dr. Miranda-Arboleda, Dr. Baranchuk, and Dr. Becker reported no conflicts of interest.

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

The ability of an Apple Watch to detect atrial fibrillation (AFib) is significantly affected by underlying ECG abnormalities such as sinus node dysfunction, atrioventricular (AV) block, or intraventricular conduction delay (IVCD), a single-center study suggests.

LDProd/Getty Images

“We were surprised to find that in one in every five patients, the smartwatch ECG failed to produce an automatic diagnosis,” study author Marc Strik, MD, PhD, a clinician at Bordeaux University Hospital in Pessac, France, told this news organization. “This [failure] was mostly due to insufficient quality of the tracing [60%], but in a third of cases, [34%], it was due to bradycardia, and in some cases, tachycardia [6%].

“We were also surprised to find that the existence of ventricular conduction disease was associated with a higher likelihood of missing AFib,” he said.

The study was published in the Canadian Journal of Cardiology.
 

Abnormalities affected detection

The investigators tested the accuracy of the Apple Watch (Apple, Cupertino, California) in detecting AFib in patients with various ECG anomalies. All participants underwent 12-lead ECG, followed by a 30-second ECG tracing with an Apple Watch Series 5. The smartwatch’s automated AFib detection algorithm gave a result of “no signs of AFib,” “AFib,” or “not checked for AFib (unclassified).”

Unclassified recordings resulted from “low heart rate” (below 50 beats/min), “high heart rate” (above 150 beats/min), “poor recording,” or “inconclusive recording.”

The smartwatch recordings were reviewed by a blinded electrophysiologist who interpreted each tracing and assigned a diagnosis of “AFib,” “absence of AFib,” or “diagnosis unclear.” To assess interobserver agreement, a second blinded electrophysiologist interpreted 100 randomly selected tracings.

Among the 734 patients (mean age, 66; 58% men) enrolled, 539 (73%) were in normal sinus rhythm (SR), 154 (21%) in AFib, 33 in atrial flutter or atrial tachycardia, 3 in ventricular tachycardia, and 5 in junctional tachycardia.

Furthermore, 65 (8.9%) had sinus node dysfunction, 21 (2.9%) had second- or third-degree AV block, 39 (5.3%) had a ventricular paced rhythm, 54 (7.4%) had premature ventricular contractions (PVCs), and 132 (18%) had IVCD (right or left bundle branch block or nonspecific IVCD).

Of the 539 patients in normal SR, 437 recordings were correctly diagnosed by the smartwatch, 7 were diagnosed incorrectly as AFib, and 95 were not classified.

Of the 187 patients in AFib, 129 were correctly diagnosed, 17 were incorrectly diagnosed as SR, and 41 were not classified.

When unclassified ECGs were considered false results, the smartwatch had a sensitivity of 69% and specificity of 81% for AFib detection. When unclassified ECGs were excluded from the analysis, sensitivity was 88%, and specificity was 98%.

Compared with patients without the abnormality, the relative risk of having false positive tracings was higher for patients with premature atrial contractions (PACs) or PVCs (risk ratio, 2.9), sinus node dysfunction (RR, 3.71), and AV block (RR, 7.8).

Fifty-eight patients with AFib were classified as SR or inconclusive by the smartwatch. Among them, 21 (36%) had an IVCD, 7 (12%) had a ventricular paced rhythm, and 5 (9%) had PACs or PVCs.

The risk of having false negative tracings (missed AF) was higher for patients with IVCD (RR, 2.6) and pacing (RR, 2.47), compared with those without the abnormality.
 

‘A powerful tool’

Overall, cardiac electrophysiologists showed high agreement in differentiating between AFib and non-AFib, with high interobserver reproducibility. A manual diagnosis was not possible for 10% of tracings because of either poor ECG quality (3%) or unclear P-waves (7%).

Fifty-nine of the 580 patients in SR were misclassified as AFib by the experts, and 5 of the 154 patients in AFib were misclassified as SR.

“Our results show that the presence of sinus node dysfunction, second- or third-degree AV block, ventricular paced rhythm, PVCs, and IVCD were more frequently represented in smartwatch misdiagnoses,” wrote the authors. “Patients with PVCs were three times as likely to have false positive AFib diagnoses.”

Study limitations included the single-center nature of the study and the fact that patients were recruited in a cardiology office. The latter factor may have influenced the incidence of ECG abnormalities, which was much higher than for the average smartwatch user.

“Even with its limitations, the smartwatch remains a powerful tool that is able to detect AFib and multiple other abnormalities,” said Dr. Strik. “Missed diagnosis of AFib may be less important in real life because of repeated measurements, and algorithms will continue to improve.”
 

Technology improving

Richard C. Becker, MD, director and physician in chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said, “This is exactly the kind of investigation required to improve upon existing detection algorithms that will someday facilitate routine use in patient care. An ability to detect AFib in a large proportion of those with the heart rhythm abnormality is encouraging.”

The findings should not detract from well-conducted studies in otherwise healthy individuals of varied age in whom AFib was accurately detected, he added. “Similarly, an automatic diagnosis algorithm for AF, pending optimization and validation in a large and diverse cohort, should be viewed as a communication tool between patients and health care providers.”

Patients at risk for developing AFib could benefit from continuous monitoring using a smartwatch, said Dr. Becker. “Pre-existing heart rhythm abnormalities must be taken into consideration. Optimal utilization of emerging technology to include wearables requires an understanding of performance and limitations. It is best undertaken in coordination with a health care provider.”

Andrés F. Miranda-Arboleda, MD, and Adrian Baranchuk, MD, of Kingston Health Sciences Center, Canada, conclude in an accompanying editorial, “In a certain manner, the smartwatch algorithms for the detection of AFib in patients with cardiovascular conditions are not yet smart enough ... but they may soon be.”

The study was supported by the French government. Dr. Strik, Dr. Miranda-Arboleda, Dr. Baranchuk, and Dr. Becker reported no conflicts of interest.

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.

ClaudioVentrella/Thinkstock

“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.

ClaudioVentrella/Thinkstock

“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.

ClaudioVentrella/Thinkstock

“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.