Marilynn Larkin

Transplantation of hearts donated after circulatory death (DCD) is associated with short-term clinical outcomes similar to those of hearts donated after brain death (DBD), except for transient posttransplant right heart dysfunction, a single-center analysis suggests.

The right-heart dysfunction resolved by 3 weeks post transplant, and recipient mortality was similar for those receiving DCD and DBD, which is considered standard of care (SOC).

Furthermore, the median waiting list time was significantly shorter for DCD recipients than for SOC recipients (17 vs. 70 days).

The authors suggest that use of DCD hearts could expand the donor pool by as much as 30%.

“Now that we and others have demonstrated the safety of this technique, I believe it is our obligation as a transplant community to use these organs and not allow them to be wasted,” David A. D’Alessandro, MD, of Massachusetts General Hospital, Boston, told this news organization.

“I will caution that DCD heart transplantation is labor intensive, and there is a learning curve which can potentially put patients at risk,” he added. “It is vitally important, therefore, that we learn from each other’s experiences to flatten this curve.”

The study was published online in the Journal of the American College of Cardiology.
 

Similar outcomes

Dr. D’Alessandro and colleagues compared the hemodynamic and clinical profiles of 47 DCD hearts with 166 SOC hearts implanted at Massachusetts General Hospital between 2016 and 2022. DCD hearts were maintained with use of a proprietary warm perfusion circuit organ care system (OCS, TransMedics).

Baseline characteristics were similar between the groups, except the DCD heart recipients were younger (mean age, 55 vs. 59); they were less likely to be an inpatient at the time of transplant (26% vs. 49%); and they had lower pulmonary vascular resistance (1.73 WU vs. 2.26 WU).

The median time from DCD consent to transplant was significantly shorter than for SOC hearts (17 vs. 70 days). However, there was a higher, though not statistically significant, incidence of severe primary graft dysfunction at 24 hours post transplant with DCD (10.6% vs. SOC 3.6%), leading five DCD recipients (10.6%) and nine SOC recipients (5.4%) to receive venoarterial extracorporeal membrane oxygenation.

Right heart function was significantly impaired in DCD vs. SOC recipients 1 week post transplant, with higher median right atrial pressure (10 mm Hg vs. 7 mm Hg); higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 vs. 0.57); and lower pulmonary arterial pulsatility index (1.66 vs. 2.52).

However, by 3 weeks post transplant, right heart function was similar between the groups, as was mortality at 30 days (0 vs. 2%) and 1 year (3% vs. 8%).

Furthermore, hospital length of stay following transplant, intensive care unit length of stay, ICU readmissions, and 30-day readmissions were similar between the groups.

“We and others will continue to push the boundaries of this technique to understand if we can safely extend the warm ischemic time, which could make additional organs available,” Dr. D’Alessandro said. “We will also be exploring additional ways to monitor and assess organ health and viability ex situ and potential avenues of treatment which could repair and optimize organ function.

“A successful DCD heart transplant program requires institutional and team commitment,” he added, “and there are clinical nuances which should be appreciated to minimize patient risks associated with the obligate learning curve.”

Ulrich P. Jorde, MD, of Montefiore Medical Center in New York, author of a related editorial, concluded that heart donation after circulatory death “promises significant expansion of the donor pool and will lead to many lives saved” and that “the current investigation is a timely and important contribution to this effort”.

However, he noted, “it must be acknowledged that donation after cardiac death has evoked significant controversy regarding the ethics of this approach,” particularly when using a technique called normothermic regional perfusion (NRP), in which, after declaration of death and ligation of cerebral vessels, the heart is resuscitated in situ using extracorporeal membrane oxygenation, as opposed to the proprietary warm perfusion OCS used in this study.

“Central to this discussion is the definition of death and its irreversibility,” Dr. Jorde noted. “In contrast to DBD, where brain death protocols are well established and accepted by societies across the globe, DCD protocol rules, e.g., standoff times after complete cessation of circulation, continue to vary even within national jurisdictions. Such variability and incomplete standardization of practice is particularly important when the organ is resuscitated in situ using normothermic regional perfusion.

“The International Society of Heart and Lung Transplantation has recently provided a framework within which donation after cardiac death, with or without the use of NRP, can be conducted to comply with ethical and legal norms and regulations, acknowledging that such norms and regulations may differ between societies,” he wrote. “To advance the field, and to ensure ongoing trust in the transplantation system, it is of critical importance that such discussions are held publicly and transparently.”
 

More ‘dry runs’

“Donor heart allographs are safe for our patients with heart failure if procured and transplanted in an organized and protocolized manner,” Philip J. Spencer, MD, a cardiovascular and transplant surgeon at Mayo Clinic in Rochester, Minn., told this news organization. “As the techniques are adopted globally, our patients will benefit.”

Nevertheless, like Dr. D’Alessandro, he noted that procurement of DCD hearts is more labor intensive. “A program and its patients must be willing to accept a higher number of ‘dry runs,’ which occurs when the team is sent for an organ and the donor does not progress to circulatory death in a time and manner appropriate for safe organ recovery.

“There is no doubt that being open to these organs will increase the patient’s chances of receiving a donor heart in a shorter period of time,” he said. “However, the experience of a dry run, or multiple, can be emotionally and financially stressful for the patient and the program.”

No commercial funding or relevant conflicts of interest were disclosed.

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

Transplantation of hearts donated after circulatory death (DCD) is associated with short-term clinical outcomes similar to those of hearts donated after brain death (DBD), except for transient posttransplant right heart dysfunction, a single-center analysis suggests.

The right-heart dysfunction resolved by 3 weeks post transplant, and recipient mortality was similar for those receiving DCD and DBD, which is considered standard of care (SOC).

Furthermore, the median waiting list time was significantly shorter for DCD recipients than for SOC recipients (17 vs. 70 days).

The authors suggest that use of DCD hearts could expand the donor pool by as much as 30%.

“Now that we and others have demonstrated the safety of this technique, I believe it is our obligation as a transplant community to use these organs and not allow them to be wasted,” David A. D’Alessandro, MD, of Massachusetts General Hospital, Boston, told this news organization.

“I will caution that DCD heart transplantation is labor intensive, and there is a learning curve which can potentially put patients at risk,” he added. “It is vitally important, therefore, that we learn from each other’s experiences to flatten this curve.”

The study was published online in the Journal of the American College of Cardiology.
 

Similar outcomes

Dr. D’Alessandro and colleagues compared the hemodynamic and clinical profiles of 47 DCD hearts with 166 SOC hearts implanted at Massachusetts General Hospital between 2016 and 2022. DCD hearts were maintained with use of a proprietary warm perfusion circuit organ care system (OCS, TransMedics).

Baseline characteristics were similar between the groups, except the DCD heart recipients were younger (mean age, 55 vs. 59); they were less likely to be an inpatient at the time of transplant (26% vs. 49%); and they had lower pulmonary vascular resistance (1.73 WU vs. 2.26 WU).

The median time from DCD consent to transplant was significantly shorter than for SOC hearts (17 vs. 70 days). However, there was a higher, though not statistically significant, incidence of severe primary graft dysfunction at 24 hours post transplant with DCD (10.6% vs. SOC 3.6%), leading five DCD recipients (10.6%) and nine SOC recipients (5.4%) to receive venoarterial extracorporeal membrane oxygenation.

Right heart function was significantly impaired in DCD vs. SOC recipients 1 week post transplant, with higher median right atrial pressure (10 mm Hg vs. 7 mm Hg); higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 vs. 0.57); and lower pulmonary arterial pulsatility index (1.66 vs. 2.52).

However, by 3 weeks post transplant, right heart function was similar between the groups, as was mortality at 30 days (0 vs. 2%) and 1 year (3% vs. 8%).

Furthermore, hospital length of stay following transplant, intensive care unit length of stay, ICU readmissions, and 30-day readmissions were similar between the groups.

“We and others will continue to push the boundaries of this technique to understand if we can safely extend the warm ischemic time, which could make additional organs available,” Dr. D’Alessandro said. “We will also be exploring additional ways to monitor and assess organ health and viability ex situ and potential avenues of treatment which could repair and optimize organ function.

“A successful DCD heart transplant program requires institutional and team commitment,” he added, “and there are clinical nuances which should be appreciated to minimize patient risks associated with the obligate learning curve.”

Ulrich P. Jorde, MD, of Montefiore Medical Center in New York, author of a related editorial, concluded that heart donation after circulatory death “promises significant expansion of the donor pool and will lead to many lives saved” and that “the current investigation is a timely and important contribution to this effort”.

However, he noted, “it must be acknowledged that donation after cardiac death has evoked significant controversy regarding the ethics of this approach,” particularly when using a technique called normothermic regional perfusion (NRP), in which, after declaration of death and ligation of cerebral vessels, the heart is resuscitated in situ using extracorporeal membrane oxygenation, as opposed to the proprietary warm perfusion OCS used in this study.

“Central to this discussion is the definition of death and its irreversibility,” Dr. Jorde noted. “In contrast to DBD, where brain death protocols are well established and accepted by societies across the globe, DCD protocol rules, e.g., standoff times after complete cessation of circulation, continue to vary even within national jurisdictions. Such variability and incomplete standardization of practice is particularly important when the organ is resuscitated in situ using normothermic regional perfusion.

“The International Society of Heart and Lung Transplantation has recently provided a framework within which donation after cardiac death, with or without the use of NRP, can be conducted to comply with ethical and legal norms and regulations, acknowledging that such norms and regulations may differ between societies,” he wrote. “To advance the field, and to ensure ongoing trust in the transplantation system, it is of critical importance that such discussions are held publicly and transparently.”
 

More ‘dry runs’

“Donor heart allographs are safe for our patients with heart failure if procured and transplanted in an organized and protocolized manner,” Philip J. Spencer, MD, a cardiovascular and transplant surgeon at Mayo Clinic in Rochester, Minn., told this news organization. “As the techniques are adopted globally, our patients will benefit.”

Nevertheless, like Dr. D’Alessandro, he noted that procurement of DCD hearts is more labor intensive. “A program and its patients must be willing to accept a higher number of ‘dry runs,’ which occurs when the team is sent for an organ and the donor does not progress to circulatory death in a time and manner appropriate for safe organ recovery.

“There is no doubt that being open to these organs will increase the patient’s chances of receiving a donor heart in a shorter period of time,” he said. “However, the experience of a dry run, or multiple, can be emotionally and financially stressful for the patient and the program.”

No commercial funding or relevant conflicts of interest were disclosed.

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

Transplantation of hearts donated after circulatory death (DCD) is associated with short-term clinical outcomes similar to those of hearts donated after brain death (DBD), except for transient posttransplant right heart dysfunction, a single-center analysis suggests.

The right-heart dysfunction resolved by 3 weeks post transplant, and recipient mortality was similar for those receiving DCD and DBD, which is considered standard of care (SOC).

Furthermore, the median waiting list time was significantly shorter for DCD recipients than for SOC recipients (17 vs. 70 days).

The authors suggest that use of DCD hearts could expand the donor pool by as much as 30%.

“Now that we and others have demonstrated the safety of this technique, I believe it is our obligation as a transplant community to use these organs and not allow them to be wasted,” David A. D’Alessandro, MD, of Massachusetts General Hospital, Boston, told this news organization.

“I will caution that DCD heart transplantation is labor intensive, and there is a learning curve which can potentially put patients at risk,” he added. “It is vitally important, therefore, that we learn from each other’s experiences to flatten this curve.”

The study was published online in the Journal of the American College of Cardiology.
 

Similar outcomes

Dr. D’Alessandro and colleagues compared the hemodynamic and clinical profiles of 47 DCD hearts with 166 SOC hearts implanted at Massachusetts General Hospital between 2016 and 2022. DCD hearts were maintained with use of a proprietary warm perfusion circuit organ care system (OCS, TransMedics).

Baseline characteristics were similar between the groups, except the DCD heart recipients were younger (mean age, 55 vs. 59); they were less likely to be an inpatient at the time of transplant (26% vs. 49%); and they had lower pulmonary vascular resistance (1.73 WU vs. 2.26 WU).

The median time from DCD consent to transplant was significantly shorter than for SOC hearts (17 vs. 70 days). However, there was a higher, though not statistically significant, incidence of severe primary graft dysfunction at 24 hours post transplant with DCD (10.6% vs. SOC 3.6%), leading five DCD recipients (10.6%) and nine SOC recipients (5.4%) to receive venoarterial extracorporeal membrane oxygenation.

Right heart function was significantly impaired in DCD vs. SOC recipients 1 week post transplant, with higher median right atrial pressure (10 mm Hg vs. 7 mm Hg); higher right atrial pressure to pulmonary capillary wedge pressure ratio (0.64 vs. 0.57); and lower pulmonary arterial pulsatility index (1.66 vs. 2.52).

However, by 3 weeks post transplant, right heart function was similar between the groups, as was mortality at 30 days (0 vs. 2%) and 1 year (3% vs. 8%).

Furthermore, hospital length of stay following transplant, intensive care unit length of stay, ICU readmissions, and 30-day readmissions were similar between the groups.

“We and others will continue to push the boundaries of this technique to understand if we can safely extend the warm ischemic time, which could make additional organs available,” Dr. D’Alessandro said. “We will also be exploring additional ways to monitor and assess organ health and viability ex situ and potential avenues of treatment which could repair and optimize organ function.

“A successful DCD heart transplant program requires institutional and team commitment,” he added, “and there are clinical nuances which should be appreciated to minimize patient risks associated with the obligate learning curve.”

Ulrich P. Jorde, MD, of Montefiore Medical Center in New York, author of a related editorial, concluded that heart donation after circulatory death “promises significant expansion of the donor pool and will lead to many lives saved” and that “the current investigation is a timely and important contribution to this effort”.

However, he noted, “it must be acknowledged that donation after cardiac death has evoked significant controversy regarding the ethics of this approach,” particularly when using a technique called normothermic regional perfusion (NRP), in which, after declaration of death and ligation of cerebral vessels, the heart is resuscitated in situ using extracorporeal membrane oxygenation, as opposed to the proprietary warm perfusion OCS used in this study.

“Central to this discussion is the definition of death and its irreversibility,” Dr. Jorde noted. “In contrast to DBD, where brain death protocols are well established and accepted by societies across the globe, DCD protocol rules, e.g., standoff times after complete cessation of circulation, continue to vary even within national jurisdictions. Such variability and incomplete standardization of practice is particularly important when the organ is resuscitated in situ using normothermic regional perfusion.

“The International Society of Heart and Lung Transplantation has recently provided a framework within which donation after cardiac death, with or without the use of NRP, can be conducted to comply with ethical and legal norms and regulations, acknowledging that such norms and regulations may differ between societies,” he wrote. “To advance the field, and to ensure ongoing trust in the transplantation system, it is of critical importance that such discussions are held publicly and transparently.”
 

More ‘dry runs’

“Donor heart allographs are safe for our patients with heart failure if procured and transplanted in an organized and protocolized manner,” Philip J. Spencer, MD, a cardiovascular and transplant surgeon at Mayo Clinic in Rochester, Minn., told this news organization. “As the techniques are adopted globally, our patients will benefit.”

Nevertheless, like Dr. D’Alessandro, he noted that procurement of DCD hearts is more labor intensive. “A program and its patients must be willing to accept a higher number of ‘dry runs,’ which occurs when the team is sent for an organ and the donor does not progress to circulatory death in a time and manner appropriate for safe organ recovery.

“There is no doubt that being open to these organs will increase the patient’s chances of receiving a donor heart in a shorter period of time,” he said. “However, the experience of a dry run, or multiple, can be emotionally and financially stressful for the patient and the program.”

No commercial funding or relevant conflicts of interest were disclosed.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Among people with HIV (PWH), coinfection with hepatitis C (HCV) is associated with an 85% increase in risk of myocardial infarction (MI) every decade, a new analysis suggests.

By contrast, the risk increases by 30% every 10 years among PWH without HCV infection.

“There is other evidence that suggests people with HIV and HCV have a greater burden of negative health outcomes,” senior author Keri N. Althoff, PhD, MPH, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. “But the magnitude of ‘greater’ was bigger than I expected.”

“Understanding the difference HCV can make in the risk of MI with increasing age among those with – compared to without – HCV is an important step for understanding additional potential benefits of HCV treatment (among PWH),” she said.

The amplified risk with age occurred even though, overall, the association between HCV coinfection and increased risk of type 1 myocardial infarction (T1MI) was not significant, the analysis showed.

The study was published online in the Journal of the American Heart Association.

How age counts

Dr. Althoff and colleagues analyzed data from 23,361 PWH aged 40-79 who had initiated antiretroviral therapy between 2000 and 2017. The primary outcome was T1MI.

A total of 4,677 participants (20%) had HCV. Eighty-nine T1MIs occurred among PWH with HCV (1.9%) vs. 314 among PWH without HCV (1.7%). In adjusted analyses, HCV was not associated with increased T1MI risk (adjusted hazard ratio, 0.98).

However, the risk of T1MI increased with age and was augmented in those with HCV (aHR per 10-year increase in age, 1.85) vs. those without HCV (aHR, 1.30).

Specifically, compared with those without HCV, the estimated T1MI risk was 17% higher among 50- to 59-year-olds with HCV and 77% higher among those 60 and older; neither association was statistically significant, although the authors suggest this probably was because of the smaller number of participants in the older age categories.

Even without HCV, the risk of T1MI increased in participants who had traditional risk factors. The risk was significantly higher among PWH aged 40-49 with diabetes, hypertension, chronic kidney disease, protease inhibitor (PI) use, and smoking, whereas among PWH aged 50-59, the T1MI risk was significantly greater among those with hypertension, PI use, and smoking.

Among those aged 60 or older, hypertension and low CD4 counts were associated with a significantly increased T1MI risk.

“Clinicians providing health care to people with HIV should know their patients’ HCV status,” Dr. Althoff said, “and provide support regarding HCV treatment and ways to reduce their cardiovascular risk, including smoking cessation, reaching and maintaining a healthy BMI, and substance use treatment.”
 

Truly additive?

American Heart Association expert volunteer Nieca Goldberg, MD, a clinical associate professor of medicine at New York University and medical director of Atria NY, said the increased T1MI risk with coinfection “makes sense” because both HIV and HCV are linked to inflammation.

However, she said in an interview, “the fact that the authors didn’t control for other, more traditional heart attack risk factors is a limitation. I would like to see a study that takes other risk factors into consideration to see if HCV is truly additive.”

Meanwhile, like Dr. Althoff, she said, “Clinicians should be taking a careful history that includes chronic infections as well as traditional heart risk factors.”

Additional studies are needed, Dr. Althoff agreed. “There are two paths we are keenly interested in pursuing. The first is understanding how metabolic risk factors for MI change after HCV treatment. We are working on this.”

“Ultimately,” she said, “we want to compare MI risk in people with HIV who had successful HCV treatment to those who have not had successful HCV treatment.”

In their current study, they had nearly 2 decades of follow-up, she noted. “Although we don’t need to wait that long, we would like to have close to a decade of potential follow-up time (since 2016, when sofosbuvir/velpatasvir became available) so that we have a large enough sample size to observe a sufficient number of MIs within the first 5 years after successful HCV treatment.”

No commercial funding or relevant disclosures were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

Elderly patients with atrial fibrillation (AF) who are at high risk of bleeding may benefit from a low 15-mg dose of edoxaban, regardless of their frailty status, a subanalysis of the ELDERCARE-AF trial suggests.  

Major bleeding and major or clinically relevant nonmajor bleeding events were both numerically higher in the edoxaban group than placebo, the authors reported, with no heterogeneity by frailty status.

The subanalysis extends findings of the overall study by teasing out stroke, systemic embolism (SSE) and bleeding events across frailty status among Japanese patients aged 80 and older who were ineligible for oral anticoagulants (OACs) at usual doses.

Findings from the original phase 3 ELDERCARE-AF study were previously reported during the virtual European Society of Cardiology Congress 2020 and simultaneously published in The New England Journal of Medicine. The current study was published online in JAMA Network Open.
 

All frailty levels benefited

Shintaro Akashi, MD, PhD, of National Hospital Organization Hamada Medical Center, Shimane, Japan, and colleagues analyzed data from 944 patients randomly assigned to edoxaban 15 mg or placebo for about 3 years. The mean age of participants was 86.6 years and 57% were women. Baseline characteristics, including history of bleeding, were similar between groups.

Patient physical condition was assessed via five parameters: weight loss, grip strength, walking speed, exhaustion, and activity level. This yielded a frailty score, with one point given for each parameter: 0 indicated robust; 1 or 2, prefrail; and 3 or higher, frail. For this analysis, robust (6.5% of patients) and prefrail (51%) were combined and categorized as nonfrail.

In the placebo group, estimated event rates for stroke or SSE were 7.1% per patient-year among frail patients and 6.1% per patient-year among those who were nonfrail.

In the edoxaban group, SSE occurred at an estimated event rate of 2.5% of frail patients and 1.5% of nonfrail patients (adjusted HR, 1.41).

The edoxaban group “consistently had fewer SSE events regardless of frailty status including each frailty assessment parameter, and there was no heterogeneity between the groups,” the authors wrote, with similar trends for the association of edoxaban 15 mg for each frailty assessment parameter.

However, major bleeding and major or clinically relevant nonmajor (CRNM) bleeding events were both higher with edoxaban, regardless of frailty status.

More specifically, in the placebo group, the incidence of major bleeding was 2.3% in the frail group and 1.5% in the nonfrail group (adjusted HR, 1.48) versus 3.7% and 2.9%, respectively, in the edoxaban group (adjusted HR, 1.04).

In addition, exhaustion was related to a significantly increased risk of major or CRNM bleeding in frail versus nonfrail patients (16.3% vs. 8.4%; adjusted HR, 1.97). The incidences were all higher in the edoxaban group, irrespective of frailty status.

Furthermore, although both all-cause death and the net clinical composite outcome of stroke or SSE occurred more frequently in frail than in nonfrail patients, there was no association with frailty status between the edoxaban and placebo groups.

Findings unrelated to edoxaban were also noteworthy. “Surprisingly, grip strength showed an association with adverse events,” the authors wrote. Among those with lower grip strength, “there was nearly a 3-fold increase in risk of SSE and major bleeding and a more than 16-fold significant increase in risk of death. In addition, in those with exhaustion, there was nearly a 2-fold significant increase in major or CRNM bleeding.”

Thus, they suggested, in this patient population, “an objective physical assessment of grip strength or exhaustion in addition to the well-known walking speed may more accurately estimate the risks of clinical outcomes than the overall frailty assessment.”

Head-to-head comparisons needed

Commenting on the findings, Richard Kovach, MD, chair of the interventional cardiology division at Deborah Heart and Lung Center, Browns Mills, N.J., said, “It is interesting that the lower dose of edoxaban still appears to have a statistically significant reduction in the incidence of stroke in this subgroup of extremely frail elderly patients, and it may be useful in this highly selected subset.

“That being said,” he added, “the major complication of oral anticoagulants – major bleeding – appears to be similar to other NOACs prescribed more frequently in the U.S., specifically rivaroxaban and apixaban.”

“Furthermore, in the U.S., frail or complex patients who are not candidates for oral anticoagulant therapy are much more likely to receive a left atrial appendage closure device such as a Watchman or Amulet in order to avoid the risk of bleeding complications completely,” he said. “Procedural success with these devices is extremely high and procedural complications are extremely low. With both devices, the long-term reduction in stroke risk is equivalent to the use of anticoagulant therapy.

“Clearly, more research is needed to compare the outcomes with edoxaban against other NOACs,” Dr. Kovach concluded. “A head-to-head comparison of low-dose edoxaban versus left atrial appendage closure in this high-risk group would also be of great clinical value.”

The study was funded by Daiichi Sankyo. Two coauthors are employees of and five have received fees from the company. Dr. Kovach has reported no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

A 5-minute bout of direct-to-consumer advertising (DTCA) for prescription heart drugs was associated with favorable perceptions of both medication use and pharmaceutical companies, but did not seem to negate intentions to use lifestyle interventions, a survey study shows.

Participants who watched ads for various prescription heart drugs, with or without price disclosure, were more likely to report positive perceptions of drug companies and intentions to take actions such as switching medications.

AlShadsky/Fotolia.com

The ads did not seem to affect intentions to eat healthfully and exercise.

The study was published online in JAMA Health Forum.
 

DTCA ‘unlikely to have an adverse effect’

“Increasing prevalence of DTCA may promote an overreliance on medication over healthy lifestyle choices to manage chronic conditions,” coauthor Yashaswini Singh, MPA, a PhD candidate at the Johns Hopkins University, Baltimore, told this news organization. “Thus, we hypothesized that DTCA exposure would reduce the likelihood of individuals engaging in preventive health behaviors.”

“However,” she said, “our results did not support this hypothesis, suggesting that exposure to DTCA for heart disease medication is unlikely to have an adverse effect on individuals’ intentions to engage in diet and exercise.”

That said, she added, “DTCA of prescription drugs can contribute to rising drug costs due to overprescribing of both inappropriate and brand-name drugs over cheaper generic alternatives. While we do not examine this mechanism in our paper, this remains an important question for future research.”

For the study, the team recruited 2,874 individuals (mean age, 53.8 years; 54% men; 83% White) from a U.S. nationally representative sample of people at high risk of cardiovascular disease, the Ipsos Public Affairs KnowledgePanel.

Participants were randomly assigned to one of three interventions: DTCA for heart disease medications, DTCA for heart disease medications with price disclosure, or nonpharmaceutical advertising (control). Each group watched five 1-minute videos for a total of 5 minutes of advertising exposure.

One group viewed ads for four heart disease medications – two ads for sacubitril/valsartan (Entresto, Novartis) and one each for rivaroxaban (Xarelto, Bayer), evolocumab (Repatha, Amgen), and ticagrelor (Brilinta, AstraZeneca); the second group saw the same ads, but with prices spliced in; and controls watched videos for nondrug products, such as consumer electronics.

Participants then completed a questionnaire to measure medication- and lifestyle-related intentions, as well as health-related beliefs and perceptions. Using a scale of 1 (highly unlikely) to 5 (highly likely), they rated the likelihood of their switching medication, asking a physician or insurer about a medication, searching for the drug online, or taking it as directed. The same scale was used to rate the likelihood of their being more physically active or eating more healthfully.

On a scale of 1 (always disagree) to 5 (always agree), they also related their perceptions of pharmaceutical manufacturers as being competent, innovative, and trustworthy.

To measure the magnitude of DTCA associations, the researchers calculated marginal effects (MEs) of treatment – that is, the difference in probability of an outcome between the treatment and control arms.

They found a positive association between DTCA and medication-related behavioral intentions, including intention to switch medication (ME, 0.004; P = .002) and engage in information-seeking behaviors (ME, 0.02; P = .01).

There was no evidence suggesting that pharmaceutical DTCA discouraged use of nonpharmacologic lifestyle interventions to help manage heart disease. DTCA also was positively associated with consumers’ favorable perceptions of pharmaceutical manufacturers (competence: ME, 0.03; P = .01; innovative: ME, 0.03; P = .008).

No differential associations were seen for price disclosures in DTCA.
 

Questions remain

The authors acknowledged that the study focused on short-term behavioral intentions and that “future research should focus on the long-term effects of advertising in a real-world randomized setting.”

Ms. Singh said additional questions, some of which her team is investigating, include “understanding the interaction between government policies [such as] drug pricing reforms and firms’ advertising decisions; understanding whether observed changes in individuals’ health beliefs translate into actual changes to information-seeking behavior and health care utilization; and whether the demographic, political, and social characteristics of individuals shape their behavioral responses to advertising.”

Johanna Contreras, MD, an advanced heart failure and transplantation cardiologist at Mount Sinai Hospital, New York, said in an interview that the findings don’t surprise her. “The caveat is that this study was an online survey, so it only captured the beliefs and intentions, but not patient demand for the product and use of the product.”

“I do believe DTCA can create positive intentions towards the product ... and could make people more receptive to interventions,” she said. However, the information must be presented in a balanced way.

In addition, she noted, “price is still important. I think people take pricing into account when deciding to proceed with an intervention. If the price is ‘right’ or a little lower than expected, then they will likely consider the product. But if the price is significantly lower, then they may not trust that it is a good product. Generic drugs are an example. Even though they are approved and far cheaper than brand names, patients are often skeptical to take them.”

The study was funded with a grant from the Blue Cross Blue Shield of Illinois Affordability Cures Consortium. Ms. Singh and coauthors disclosed no relevant financial relationships.

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

Among children born prematurely, rates of school readiness were lower, compared with rates for children born full term, new data indicate.

In a Canadian cohort study that included more than 60,000 children, 35% of children born prematurely had scores on the Early Development Instrument (EDI) that indicated they were vulnerable to developmental problems, compared with 28% of children born full term.

“Our take-home message is that being born prematurely, even if all was well, is a risk factor for not being ready for school, and these families should be identified early, screened for any difficulties, and offered early intervention,” senior author Chelsea A. Ruth, MD, assistant professor of pediatrics and child health at the University of Manitoba, Winnipeg, told this news organization.

The findings were published online in JAMA Pediatrics.
 

Gestational age gradient

The investigators examined two cohorts of children who were in kindergarten at the time of data collection. One of them, the population-based cohort, included children born between 2000 and 2011 whose school readiness was assessed using the EDI data. Preterm birth was defined as a gestational age (GA) of less than 37 weeks. The other, the sibling cohort, was a subset of the population cohort and included children born prematurely and their closest-in-age siblings who were born full term.

The main outcome was vulnerability in the EDI, which was defined as having a score below the 10th percentile of the Canadian population norms for one or more of the five EDI domains. These domains are physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge.

A total of 63,277 children were included in the analyses, of whom 4,352 were born prematurely (mean GA, 34 weeks; 53% boys) and 58,925 were born full term (mean GA, 39 weeks; 51% boys).

After data adjustment, 35% of children born prematurely were vulnerable in the EDI, compared with 28% of those born full term (adjusted odds ratio, 1.32).

The investigators found a clear GA gradient. Children born at earlier GAs (< 28 weeks or 28-33 weeks) were at higher risk of being vulnerable than those born at later GAs (34-36 weeks) in any EDI domain (48% vs. 40%) and in each of the five EDI domains. Earlier GA was associated with greater risk for vulnerability in physical health and well-being (34% vs. 22%) and in the Multiple Challenge Index (25% vs. 17%). It also was associated with greater risk for need for additional support in kindergarten (22% vs. 5%).

Furthermore, 12% of children born at less than 28 weeks’ gestation were vulnerable in two EDI domains, and 8% were vulnerable in three domains. The corresponding proportions were 9% and 7%, respectively, for those born between 28 and 33 weeks and 7% and 5% for those born between 34 and 36 weeks.

“The study confirmed what we see in practice, that being born even a little bit early increases the chance for not being ready for school, and the earlier a child is born, the more likely they are to have troubles,” said Dr. Ruth.
 

Cause or manifestation?

In the population cohort, prematurity (< 34 weeks’ GA: AOR, 1.72; 34-36 weeks’ GA: AOR, 1.23), male sex (AOR, 2.24), small for GA (AOR, 1.31), and various maternal medical and sociodemographic factors were associated with EDI vulnerability.

In the sibling subset, EDI outcomes were similar for children born prematurely and their siblings born full term, except for the communication skills and general knowledge domain (AOR, 1.39) and the Multiple Challenge Index (AOR, 1.43). Male sex (AOR, 2.19) was associated with EDI vulnerability in this cohort as well, as was maternal age at delivery (AOR, 1.53).

“Whether prematurity is a cause or a manifestation of an altered family ecosystem is difficult to ascertain,” Lauren Neel, MD, a neonatologist at Emory University, Atlanta, and colleagues write in an accompanying editorial. “However, research on this topic is much needed, along with novel interventions to change academic trajectories and care models that implement these findings in practice. As we begin to understand the factors in and interventions for promoting resilience in preterm-born children, we may need to change our research question to this: Could we optimize resilience and long-term academic trajectories to include the family as well?”
 

Six crucial years

Commenting on the study, Veronica Bordes Edgar, PhD, associate professor of psychiatry and pediatrics at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, Dallas, said, “None of the findings surprised me, but I was very pleased that they looked at such a broad sample.”

Pediatricians should monitor and screen children for early academic readiness, since these factors are associated with later academic outcomes, Dr. Edgar added. “Early intervention does not stop at age 3, but rather the first 6 years are so crucial to lay the foundation for future success. The pediatrician can play a role in preparing children and families by promoting early reading, such as through Reach Out and Read, encouraging language-rich play, and providing guidance on early childhood education and developmental needs.

“Further examination of long-term outcomes for these children to capture the longitudinal trend would help to document what is often observed clinically, in that children who start off with difficulties do not always catch up once they are in the academic environment,” Dr. Edgar concluded.

The study was supported by Research Manitoba and the Children’s Research Institute of Manitoba. Dr. Ruth, Dr. Neel, and Dr. Edgar have disclosed no relevant financial relationships.

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

Among children born prematurely, rates of school readiness were lower, compared with rates for children born full term, new data indicate.

In a Canadian cohort study that included more than 60,000 children, 35% of children born prematurely had scores on the Early Development Instrument (EDI) that indicated they were vulnerable to developmental problems, compared with 28% of children born full term.

“Our take-home message is that being born prematurely, even if all was well, is a risk factor for not being ready for school, and these families should be identified early, screened for any difficulties, and offered early intervention,” senior author Chelsea A. Ruth, MD, assistant professor of pediatrics and child health at the University of Manitoba, Winnipeg, told this news organization.

The findings were published online in JAMA Pediatrics.
 

Gestational age gradient

The investigators examined two cohorts of children who were in kindergarten at the time of data collection. One of them, the population-based cohort, included children born between 2000 and 2011 whose school readiness was assessed using the EDI data. Preterm birth was defined as a gestational age (GA) of less than 37 weeks. The other, the sibling cohort, was a subset of the population cohort and included children born prematurely and their closest-in-age siblings who were born full term.

The main outcome was vulnerability in the EDI, which was defined as having a score below the 10th percentile of the Canadian population norms for one or more of the five EDI domains. These domains are physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge.

A total of 63,277 children were included in the analyses, of whom 4,352 were born prematurely (mean GA, 34 weeks; 53% boys) and 58,925 were born full term (mean GA, 39 weeks; 51% boys).

After data adjustment, 35% of children born prematurely were vulnerable in the EDI, compared with 28% of those born full term (adjusted odds ratio, 1.32).

The investigators found a clear GA gradient. Children born at earlier GAs (< 28 weeks or 28-33 weeks) were at higher risk of being vulnerable than those born at later GAs (34-36 weeks) in any EDI domain (48% vs. 40%) and in each of the five EDI domains. Earlier GA was associated with greater risk for vulnerability in physical health and well-being (34% vs. 22%) and in the Multiple Challenge Index (25% vs. 17%). It also was associated with greater risk for need for additional support in kindergarten (22% vs. 5%).

Furthermore, 12% of children born at less than 28 weeks’ gestation were vulnerable in two EDI domains, and 8% were vulnerable in three domains. The corresponding proportions were 9% and 7%, respectively, for those born between 28 and 33 weeks and 7% and 5% for those born between 34 and 36 weeks.

“The study confirmed what we see in practice, that being born even a little bit early increases the chance for not being ready for school, and the earlier a child is born, the more likely they are to have troubles,” said Dr. Ruth.
 

Cause or manifestation?

In the population cohort, prematurity (< 34 weeks’ GA: AOR, 1.72; 34-36 weeks’ GA: AOR, 1.23), male sex (AOR, 2.24), small for GA (AOR, 1.31), and various maternal medical and sociodemographic factors were associated with EDI vulnerability.

In the sibling subset, EDI outcomes were similar for children born prematurely and their siblings born full term, except for the communication skills and general knowledge domain (AOR, 1.39) and the Multiple Challenge Index (AOR, 1.43). Male sex (AOR, 2.19) was associated with EDI vulnerability in this cohort as well, as was maternal age at delivery (AOR, 1.53).

“Whether prematurity is a cause or a manifestation of an altered family ecosystem is difficult to ascertain,” Lauren Neel, MD, a neonatologist at Emory University, Atlanta, and colleagues write in an accompanying editorial. “However, research on this topic is much needed, along with novel interventions to change academic trajectories and care models that implement these findings in practice. As we begin to understand the factors in and interventions for promoting resilience in preterm-born children, we may need to change our research question to this: Could we optimize resilience and long-term academic trajectories to include the family as well?”
 

Six crucial years

Commenting on the study, Veronica Bordes Edgar, PhD, associate professor of psychiatry and pediatrics at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, Dallas, said, “None of the findings surprised me, but I was very pleased that they looked at such a broad sample.”

Pediatricians should monitor and screen children for early academic readiness, since these factors are associated with later academic outcomes, Dr. Edgar added. “Early intervention does not stop at age 3, but rather the first 6 years are so crucial to lay the foundation for future success. The pediatrician can play a role in preparing children and families by promoting early reading, such as through Reach Out and Read, encouraging language-rich play, and providing guidance on early childhood education and developmental needs.

“Further examination of long-term outcomes for these children to capture the longitudinal trend would help to document what is often observed clinically, in that children who start off with difficulties do not always catch up once they are in the academic environment,” Dr. Edgar concluded.

The study was supported by Research Manitoba and the Children’s Research Institute of Manitoba. Dr. Ruth, Dr. Neel, and Dr. Edgar have disclosed no relevant financial relationships.

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

Among children born prematurely, rates of school readiness were lower, compared with rates for children born full term, new data indicate.

In a Canadian cohort study that included more than 60,000 children, 35% of children born prematurely had scores on the Early Development Instrument (EDI) that indicated they were vulnerable to developmental problems, compared with 28% of children born full term.

“Our take-home message is that being born prematurely, even if all was well, is a risk factor for not being ready for school, and these families should be identified early, screened for any difficulties, and offered early intervention,” senior author Chelsea A. Ruth, MD, assistant professor of pediatrics and child health at the University of Manitoba, Winnipeg, told this news organization.

The findings were published online in JAMA Pediatrics.
 

Gestational age gradient

The investigators examined two cohorts of children who were in kindergarten at the time of data collection. One of them, the population-based cohort, included children born between 2000 and 2011 whose school readiness was assessed using the EDI data. Preterm birth was defined as a gestational age (GA) of less than 37 weeks. The other, the sibling cohort, was a subset of the population cohort and included children born prematurely and their closest-in-age siblings who were born full term.

The main outcome was vulnerability in the EDI, which was defined as having a score below the 10th percentile of the Canadian population norms for one or more of the five EDI domains. These domains are physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge.

A total of 63,277 children were included in the analyses, of whom 4,352 were born prematurely (mean GA, 34 weeks; 53% boys) and 58,925 were born full term (mean GA, 39 weeks; 51% boys).

After data adjustment, 35% of children born prematurely were vulnerable in the EDI, compared with 28% of those born full term (adjusted odds ratio, 1.32).

The investigators found a clear GA gradient. Children born at earlier GAs (< 28 weeks or 28-33 weeks) were at higher risk of being vulnerable than those born at later GAs (34-36 weeks) in any EDI domain (48% vs. 40%) and in each of the five EDI domains. Earlier GA was associated with greater risk for vulnerability in physical health and well-being (34% vs. 22%) and in the Multiple Challenge Index (25% vs. 17%). It also was associated with greater risk for need for additional support in kindergarten (22% vs. 5%).

Furthermore, 12% of children born at less than 28 weeks’ gestation were vulnerable in two EDI domains, and 8% were vulnerable in three domains. The corresponding proportions were 9% and 7%, respectively, for those born between 28 and 33 weeks and 7% and 5% for those born between 34 and 36 weeks.

“The study confirmed what we see in practice, that being born even a little bit early increases the chance for not being ready for school, and the earlier a child is born, the more likely they are to have troubles,” said Dr. Ruth.
 

Cause or manifestation?

In the population cohort, prematurity (< 34 weeks’ GA: AOR, 1.72; 34-36 weeks’ GA: AOR, 1.23), male sex (AOR, 2.24), small for GA (AOR, 1.31), and various maternal medical and sociodemographic factors were associated with EDI vulnerability.

In the sibling subset, EDI outcomes were similar for children born prematurely and their siblings born full term, except for the communication skills and general knowledge domain (AOR, 1.39) and the Multiple Challenge Index (AOR, 1.43). Male sex (AOR, 2.19) was associated with EDI vulnerability in this cohort as well, as was maternal age at delivery (AOR, 1.53).

“Whether prematurity is a cause or a manifestation of an altered family ecosystem is difficult to ascertain,” Lauren Neel, MD, a neonatologist at Emory University, Atlanta, and colleagues write in an accompanying editorial. “However, research on this topic is much needed, along with novel interventions to change academic trajectories and care models that implement these findings in practice. As we begin to understand the factors in and interventions for promoting resilience in preterm-born children, we may need to change our research question to this: Could we optimize resilience and long-term academic trajectories to include the family as well?”
 

Six crucial years

Commenting on the study, Veronica Bordes Edgar, PhD, associate professor of psychiatry and pediatrics at the University of Texas Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute, Dallas, said, “None of the findings surprised me, but I was very pleased that they looked at such a broad sample.”

Pediatricians should monitor and screen children for early academic readiness, since these factors are associated with later academic outcomes, Dr. Edgar added. “Early intervention does not stop at age 3, but rather the first 6 years are so crucial to lay the foundation for future success. The pediatrician can play a role in preparing children and families by promoting early reading, such as through Reach Out and Read, encouraging language-rich play, and providing guidance on early childhood education and developmental needs.

“Further examination of long-term outcomes for these children to capture the longitudinal trend would help to document what is often observed clinically, in that children who start off with difficulties do not always catch up once they are in the academic environment,” Dr. Edgar concluded.

The study was supported by Research Manitoba and the Children’s Research Institute of Manitoba. Dr. Ruth, Dr. Neel, and Dr. Edgar have disclosed no relevant financial relationships.

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

Cardiorespiratory fitness emerged as a stronger predictor of all-cause mortality than did any traditional risk factor across the spectrum of age, sex, and race in a modeling study that included more than 750,000 U.S. veterans.

In addition, mortality risk was cut in half if individuals achieved a moderate cardiorespiratory fitness (CRF) level – that is, by meeting the current U.S. physical activity recommendations of 150 minutes per week, the authors note.

Furthermore, contrary to some previous research, “extremely high” fitness was not associated with an increased risk for mortality in the study, published online in the Journal of the American College of Cardiology.

“This study has been 15 years in the making,” lead author Peter Kokkinos, PhD, Rutgers University, New Brunswick, N.J., and the VA Medical Center, Washington, told this news organization. “We waited until we had the computer power and the right people to really assess this. We wanted to be very liberal in excluding patients we thought might contaminate the results, such as those with cardiovascular disease in the 6 months prior to a stress test.”

Figuring the time was right, the team analyzed data from the VA’s Exercise Testing and Health Outcomes Study (ETHOS) on individuals aged 30-95 years who underwent exercise treadmill tests between 1999 and 2020.

After exclusions, 750,302 individuals (from among 822,995) were included: 6.5% were women; 73.7% were White individuals; 19% were African American individuals; 4.7% were Hispanic individuals; and 2.1% were Native American, Asian, or Hawaiian individuals. Septuagenarians made up 14.7% of the cohort, and octogenarians made up 3.6%.

CRF categories for age and sex were determined by the peak metabolic equivalent of task (MET) achieved during the treadmill test. One MET is the energy spent at rest – that is the basal metabolic rate.

Although some physicians may resist putting patients through a stress test, “the amount of information we get from it is incredible,” Dr. Kokkinos noted. “We get blood pressure, we get heart rate, we get a response if you’re not doing exercise. This tells us a lot more than having you sit around so we can measure resting heart rate and blood pressure.”

Lowest mortality at 14.0 METs

During a median follow-up of 10.2 years (7,803,861 person-years), 23% of participants died, for an average of 22.4 events per 1,000 person-years.

Higher exercise capacity was inversely related to mortality risk across the cohort and within each age category. Specifically, every 1 MET increase in exercise capacity yielded an adjusted hazard ratio for mortality of 0.86 (95% confidence interval, 0.85-0.87; P < .001) for the entire cohort and similar HRs by sex and race.

The mortality risk for the least-fit individuals (20th percentile) was fourfold higher than for extremely fit individuals (HR, 4.09; 95% CI, 3.90-4.20), with the lowest mortality risk at about 14.0 METs for both men (HR, 0.24; 95% CI, 0.23-0.25) and women (HR, 0.23; 95% CI, 0.17-0.29). Extremely high CRF did not increase the risk.

In addition, at 20 years of follow-up, about 80% of men and 95% of women in the highest CRF category (98th percentile) were alive vs. less than 40% of men and approximately 75% of women in the least fit CRF category.

“We know CRF declines by 1% per year after age 30,” Dr. Kokkinos said. “But the age-related decline is cut in half if you are fit, meaning that an expected 10% decline over a decade will be only a 5% decline if you stay active. We cannot stop or reverse the decline, but we can kind of put the brakes on, and that’s a reason for clinicians to continue to encourage fitness.” 

Indeed, “improving CRF should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight,” Carl J. Lavie, MD, Ochsner Health, New Orleans, and colleagues affirm in a related editorial.
 

‘A difficult battle’

But that may not happen any time soon. “Unfortunately, despite having been recognized in an American Heart Association scientific statement as a clinical vital sign, aerobic fitness is undervalued and underutilized,” Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX, Rio de Janeiro, told this news organization.

Dr. Araújo led a recent study showing that the ability to stand on one leg for at least 10 seconds is strongly linked to the risk for death over the next 7 years.

Although physicians should be encouraging fitness, he said that “a substantial part of health professionals are physically unfit and feel uncomfortable talking about and prescribing exercise for their patients. Also, physicians tend to be better trained in treating diseases (using medications and/or prescribing procedures) than in preventing diseases by stimulating adoption of healthy habits. So, this a long road and a difficult battle.”

Nonetheless, he added, “Darwin said a long time ago that only the fittest will survive. If Darwin could read this study, he would surely smile.”

No commercial funding or conflicts of interest related to the study were reported. Dr. Lavie previously served as a speaker and consultant for PAI Health on their PAI (Personalized Activity Intelligence) applications.

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

Cardiorespiratory fitness emerged as a stronger predictor of all-cause mortality than did any traditional risk factor across the spectrum of age, sex, and race in a modeling study that included more than 750,000 U.S. veterans.

In addition, mortality risk was cut in half if individuals achieved a moderate cardiorespiratory fitness (CRF) level – that is, by meeting the current U.S. physical activity recommendations of 150 minutes per week, the authors note.

Furthermore, contrary to some previous research, “extremely high” fitness was not associated with an increased risk for mortality in the study, published online in the Journal of the American College of Cardiology.

“This study has been 15 years in the making,” lead author Peter Kokkinos, PhD, Rutgers University, New Brunswick, N.J., and the VA Medical Center, Washington, told this news organization. “We waited until we had the computer power and the right people to really assess this. We wanted to be very liberal in excluding patients we thought might contaminate the results, such as those with cardiovascular disease in the 6 months prior to a stress test.”

Figuring the time was right, the team analyzed data from the VA’s Exercise Testing and Health Outcomes Study (ETHOS) on individuals aged 30-95 years who underwent exercise treadmill tests between 1999 and 2020.

After exclusions, 750,302 individuals (from among 822,995) were included: 6.5% were women; 73.7% were White individuals; 19% were African American individuals; 4.7% were Hispanic individuals; and 2.1% were Native American, Asian, or Hawaiian individuals. Septuagenarians made up 14.7% of the cohort, and octogenarians made up 3.6%.

CRF categories for age and sex were determined by the peak metabolic equivalent of task (MET) achieved during the treadmill test. One MET is the energy spent at rest – that is the basal metabolic rate.

Although some physicians may resist putting patients through a stress test, “the amount of information we get from it is incredible,” Dr. Kokkinos noted. “We get blood pressure, we get heart rate, we get a response if you’re not doing exercise. This tells us a lot more than having you sit around so we can measure resting heart rate and blood pressure.”

Lowest mortality at 14.0 METs

During a median follow-up of 10.2 years (7,803,861 person-years), 23% of participants died, for an average of 22.4 events per 1,000 person-years.

Higher exercise capacity was inversely related to mortality risk across the cohort and within each age category. Specifically, every 1 MET increase in exercise capacity yielded an adjusted hazard ratio for mortality of 0.86 (95% confidence interval, 0.85-0.87; P < .001) for the entire cohort and similar HRs by sex and race.

The mortality risk for the least-fit individuals (20th percentile) was fourfold higher than for extremely fit individuals (HR, 4.09; 95% CI, 3.90-4.20), with the lowest mortality risk at about 14.0 METs for both men (HR, 0.24; 95% CI, 0.23-0.25) and women (HR, 0.23; 95% CI, 0.17-0.29). Extremely high CRF did not increase the risk.

In addition, at 20 years of follow-up, about 80% of men and 95% of women in the highest CRF category (98th percentile) were alive vs. less than 40% of men and approximately 75% of women in the least fit CRF category.

“We know CRF declines by 1% per year after age 30,” Dr. Kokkinos said. “But the age-related decline is cut in half if you are fit, meaning that an expected 10% decline over a decade will be only a 5% decline if you stay active. We cannot stop or reverse the decline, but we can kind of put the brakes on, and that’s a reason for clinicians to continue to encourage fitness.” 

Indeed, “improving CRF should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight,” Carl J. Lavie, MD, Ochsner Health, New Orleans, and colleagues affirm in a related editorial.
 

‘A difficult battle’

But that may not happen any time soon. “Unfortunately, despite having been recognized in an American Heart Association scientific statement as a clinical vital sign, aerobic fitness is undervalued and underutilized,” Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX, Rio de Janeiro, told this news organization.

Dr. Araújo led a recent study showing that the ability to stand on one leg for at least 10 seconds is strongly linked to the risk for death over the next 7 years.

Although physicians should be encouraging fitness, he said that “a substantial part of health professionals are physically unfit and feel uncomfortable talking about and prescribing exercise for their patients. Also, physicians tend to be better trained in treating diseases (using medications and/or prescribing procedures) than in preventing diseases by stimulating adoption of healthy habits. So, this a long road and a difficult battle.”

Nonetheless, he added, “Darwin said a long time ago that only the fittest will survive. If Darwin could read this study, he would surely smile.”

No commercial funding or conflicts of interest related to the study were reported. Dr. Lavie previously served as a speaker and consultant for PAI Health on their PAI (Personalized Activity Intelligence) applications.

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

Cardiorespiratory fitness emerged as a stronger predictor of all-cause mortality than did any traditional risk factor across the spectrum of age, sex, and race in a modeling study that included more than 750,000 U.S. veterans.

In addition, mortality risk was cut in half if individuals achieved a moderate cardiorespiratory fitness (CRF) level – that is, by meeting the current U.S. physical activity recommendations of 150 minutes per week, the authors note.

Furthermore, contrary to some previous research, “extremely high” fitness was not associated with an increased risk for mortality in the study, published online in the Journal of the American College of Cardiology.

“This study has been 15 years in the making,” lead author Peter Kokkinos, PhD, Rutgers University, New Brunswick, N.J., and the VA Medical Center, Washington, told this news organization. “We waited until we had the computer power and the right people to really assess this. We wanted to be very liberal in excluding patients we thought might contaminate the results, such as those with cardiovascular disease in the 6 months prior to a stress test.”

Figuring the time was right, the team analyzed data from the VA’s Exercise Testing and Health Outcomes Study (ETHOS) on individuals aged 30-95 years who underwent exercise treadmill tests between 1999 and 2020.

After exclusions, 750,302 individuals (from among 822,995) were included: 6.5% were women; 73.7% were White individuals; 19% were African American individuals; 4.7% were Hispanic individuals; and 2.1% were Native American, Asian, or Hawaiian individuals. Septuagenarians made up 14.7% of the cohort, and octogenarians made up 3.6%.

CRF categories for age and sex were determined by the peak metabolic equivalent of task (MET) achieved during the treadmill test. One MET is the energy spent at rest – that is the basal metabolic rate.

Although some physicians may resist putting patients through a stress test, “the amount of information we get from it is incredible,” Dr. Kokkinos noted. “We get blood pressure, we get heart rate, we get a response if you’re not doing exercise. This tells us a lot more than having you sit around so we can measure resting heart rate and blood pressure.”

Lowest mortality at 14.0 METs

During a median follow-up of 10.2 years (7,803,861 person-years), 23% of participants died, for an average of 22.4 events per 1,000 person-years.

Higher exercise capacity was inversely related to mortality risk across the cohort and within each age category. Specifically, every 1 MET increase in exercise capacity yielded an adjusted hazard ratio for mortality of 0.86 (95% confidence interval, 0.85-0.87; P < .001) for the entire cohort and similar HRs by sex and race.

The mortality risk for the least-fit individuals (20th percentile) was fourfold higher than for extremely fit individuals (HR, 4.09; 95% CI, 3.90-4.20), with the lowest mortality risk at about 14.0 METs for both men (HR, 0.24; 95% CI, 0.23-0.25) and women (HR, 0.23; 95% CI, 0.17-0.29). Extremely high CRF did not increase the risk.

In addition, at 20 years of follow-up, about 80% of men and 95% of women in the highest CRF category (98th percentile) were alive vs. less than 40% of men and approximately 75% of women in the least fit CRF category.

“We know CRF declines by 1% per year after age 30,” Dr. Kokkinos said. “But the age-related decline is cut in half if you are fit, meaning that an expected 10% decline over a decade will be only a 5% decline if you stay active. We cannot stop or reverse the decline, but we can kind of put the brakes on, and that’s a reason for clinicians to continue to encourage fitness.” 

Indeed, “improving CRF should be considered a target in CVD prevention, similar to improving lipids, blood sugar, blood pressure, and weight,” Carl J. Lavie, MD, Ochsner Health, New Orleans, and colleagues affirm in a related editorial.
 

‘A difficult battle’

But that may not happen any time soon. “Unfortunately, despite having been recognized in an American Heart Association scientific statement as a clinical vital sign, aerobic fitness is undervalued and underutilized,” Claudio Gil Araújo, MD, PhD, research director of the Exercise Medicine Clinic-CLINIMEX, Rio de Janeiro, told this news organization.

Dr. Araújo led a recent study showing that the ability to stand on one leg for at least 10 seconds is strongly linked to the risk for death over the next 7 years.

Although physicians should be encouraging fitness, he said that “a substantial part of health professionals are physically unfit and feel uncomfortable talking about and prescribing exercise for their patients. Also, physicians tend to be better trained in treating diseases (using medications and/or prescribing procedures) than in preventing diseases by stimulating adoption of healthy habits. So, this a long road and a difficult battle.”

Nonetheless, he added, “Darwin said a long time ago that only the fittest will survive. If Darwin could read this study, he would surely smile.”

No commercial funding or conflicts of interest related to the study were reported. Dr. Lavie previously served as a speaker and consultant for PAI Health on their PAI (Personalized Activity Intelligence) applications.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

Cardiovascular disease (CVD) mortality rose significantly during the COVID-19 pandemic and persists more than 2 years on and, once again, Blacks and African Americans have been disproportionately affected, an analysis of death certificates shows.

The findings “suggest that the pandemic may reverse years or decades of work aimed at reducing gaps in cardiovascular outcomes,” Sadeer G. Al-Kindi, MD, Case Western Reserve University, Cleveland, said in an interview.

Although the disparities are in line with previous research, he said, “what was surprising is the persistence of excess cardiovascular mortality approximately 2 years after the pandemic started, even during a period of low COVID-19 mortality.”

“This suggests that the pandemic resulted in a disruption of health care access and, along with disparities in COVID-19 infection and its complications, he said, “may have a long-lasting effect on health care disparities, especially among vulnerable populations.”

The study was published online in Mayo Clinic Proceedings with lead author Scott E. Janus, MD, also of Case Western Reserve University.
 

Impact consistently greater for Blacks

Dr. Al-Kindi and colleagues used 3,598,352 U.S. death files to investigate trends in deaths caused specifically by CVD as well as its subtypes myocardial infarction, stroke, and heart failure (HF) in 2018 and 2019 (prepandemic) and the pandemic years 2020 and 2021. Baseline demographics showed a higher percentage of older, female, and Black individuals among the CVD subtypes of interest.

Overall, there was an excess CVD mortality of 6.7% during the pandemic, compared with prepandemic years, including a 2.5% rise in MI deaths and an 8.5% rise in stroke deaths. HF mortality remained relatively steady, rising only 0.1%.

Subgroup analyses revealed “striking differences” in excess mortality between Blacks and Whites, the authors noted. Blacks had an overall excess mortality of 13.8% versus 5.1% for Whites, compared with the prepandemic years. The differences were consistent across subtypes: MI (9.6% vs. 1.0%); stroke (14.5% vs. 6.9%); and HF (5.1% vs. –1.2%; P value for all < .001).

When the investigators looked at deaths on a yearly basis with 2018 as the baseline, they found CVD deaths increased by 1.5% in 2019, 15.8% in 2020, and 13.5% in 2021 among Black Americans, compared with 0.5%, 5.1%, and 5.7%, respectively, among White Americans.

Excess deaths from MI rose by 9.5% in 2020 and by 6.7% in 2021 among Blacks but fell by 1.2% in 2020 and by 1.0% in 2021 among Whites.

Disparities in excess HF mortality were similar, rising 9.1% and 4.1% in 2020 and 2021 among Blacks, while dipping 0.1% and 0.8% in 2020 and 2021 among Whites.

The “most striking difference” was in excess stroke mortality, which doubled among Blacks compared with whites in 2020 (14.9% vs. 6.7%) and in 2021 (17.5% vs. 8.1%), according to the authors.
 

Awareness urged

Although the disparities were expected, “there is clear value in documenting and quantifying the magnitude of these disparities,” Amil M. Shah, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital, both in Boston, said in an interview.

In addition to being observational, the main limitation of the study, he noted, is the quality and resolution of the death certificate data, which may limit the accuracy of the cause of death ascertainment and classification of race or ethnicity. “However, I think these potential inaccuracies are unlikely to materially impact the overall study findings.”

Dr. Shah, who was not involved in the study, said he would like to see additional research into the diversity and heterogeneity in risk among Black communities. “Understanding the environmental, social, and health care factors – both harmful and protective – that influence risk for CVD morbidity and mortality among Black individuals and communities offers the promise to provide actionable insights to mitigate these disparities.”

“Intervention studies testing approaches to mitigate disparities based on race/ethnicity” are also needed, he added. These may be at the policy, community, health system, or individual level, and community involvement in phases will be essential.”

Meanwhile, both Dr. Al-Kindi and Dr. Shah urged clinicians to be aware of the disparities and the need to improve access to care and address social determinants of health in vulnerable populations.

These disparities “are driven by structural factors, and are reinforced by individual behaviors. In this context, implicit bias training is important to help clinicians recognize and mitigate bias in their own practice,” Dr. Shah said. “Supporting diversity, equity, and inclusion efforts, and advocating for anti-racist policies and practices in their health systems” can also help.

Dr. Al-Kindi and Dr. Shah disclosed no relevant financial relationships.

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

If 80% of individuals with hypertension were screened, 80% received treatment, and 80% then reached guideline-specified targets, up to 200 million cases of cardiovascular disease (CVD) and 130 million deaths could be averted by 2050, a modeling study suggests.

Achievement of the 80-80-80 target “could be one of the single most important global public health accomplishments of the coming decades,” according to the authors.

“We need to reprioritize hypertension care in our practices,” principal investigator David A. Watkins, MD, MPH, University of Washington, Seattle, told this news organization. “Only about one in five persons with hypertension around the world has their blood pressure well controlled. Oftentimes, clinicians are focused on addressing patients’ other health needs, many of which can be pressing in the short term, and we forget to talk about blood pressure, which has more than earned its reputation as ‘the silent killer.’ ”

The modeling study was published online  in Nature Medicine, with lead author Sarah J. Pickersgill, MPH, also from the University of Washington.
 

Two interventions, three scenarios

Dr. Watkins and colleagues based their analysis on two approaches to blood pressure (BP) control shown to be beneficial: drug treatment to a systolic BP of either 130 mm Hg or 140 mm Hg or less, depending on local guidelines, and dietary sodium reduction, as recommended by the World Health Organization.

The team modeled the impacts of these interventions in 182 countries according to three scenarios:

• Business as usual (control): allowing hypertension to increase at historic rates of change and mean sodium intake to remain at current levels
• Progress: matching historically high-performing countries (for example, accelerating hypertension control by about 3% per year at intermediate levels of intervention coverage) while lowering mean sodium intake by 15% by 2030
• Aspirational: hypertension control achieved faster than historically high-performing countries (about 4% per year) and mean sodium intake decreased by 30% by 2027

The analysis suggests that in the progressive scenario, all countries could achieve 80-80-80 targets by 2050 and most countries by 2040; the aspirational scenario would have all countries meeting them by 2040. That would result in reductions in all-cause mortality of 4%-7% (76 million to 130 million deaths averted) with progressive and aspirational interventions, respectively, compared with the control scenario.

There would also be a slower rise in expected CVD from population growth and aging (110 million to 200 million cases averted). That is, the probability of dying from any CVD cause between the ages of 30 and 80 years would be reduced by 16% in the progressive scenario and 26% in the aspirational scenario.

Of note, about 83%-85% of the potential mortality reductions would result from scaling up hypertension treatment in the progressive and aspirational scenarios, respectively, with the remaining 15%-17% coming from sodium reduction, the researchers state.

Further, they propose, scaling up BP interventions could reduce CVD inequalities across countries, with low-income and lower-middle-income countries likely experiencing the largest reductions in disease rates and mortality.
 

Implementation barriers

“Health systems in many low- and middle-income countries have not traditionally been set up to succeed in chronic disease management in primary care,” Dr. Watkins noted. For interventions to be successful, he said, “several barriers need to be addressed, including: low population awareness of chronic diseases like hypertension and diabetes, which leads to low rates of screening and treatment; high out-of-pocket cost and low availability of medicines for chronic diseases; and need for adherence support and provider incentives for improving quality of chronic disease care in primary care settings.”

“Based on the analysis, achieving the 80-80-80 seems feasible, though actually getting there may be much more complicated. I wonder whether countries have the resources to implement the needed policies,” Rodrigo M. Carrillo-Larco, MD, researcher, department of epidemiology and biostatistics, School of Public Health, Imperial College London, told this news organization.

“It may be challenging, particularly after COVID-19, which revealed deficiencies in many health care systems, and care for hypertension may have been disturbed,” said Dr. Carrillo-Larco, who is not connected with the analysis.

That said, simplified BP screening approaches could help maximize the number of people screened overall, potentially identifying those with hypertension and raising awareness, he proposed. His team’s recent study showed that such approaches vary from country to country but are generally reliable and can be used effectively for population screening.

In addition, Dr. Carrillo-Larco said, any efforts by clinicians to improve adherence and help patients achieve BP control “would also have positive effects at the population level.”

The study was supported by a grant from the Bill & Melinda Gates Foundation, with additional funding by a grant to Dr. Watkins from Resolve to Save Lives. No conflicts of interest were declared.

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

If 80% of individuals with hypertension were screened, 80% received treatment, and 80% then reached guideline-specified targets, up to 200 million cases of cardiovascular disease (CVD) and 130 million deaths could be averted by 2050, a modeling study suggests.

Achievement of the 80-80-80 target “could be one of the single most important global public health accomplishments of the coming decades,” according to the authors.

“We need to reprioritize hypertension care in our practices,” principal investigator David A. Watkins, MD, MPH, University of Washington, Seattle, told this news organization. “Only about one in five persons with hypertension around the world has their blood pressure well controlled. Oftentimes, clinicians are focused on addressing patients’ other health needs, many of which can be pressing in the short term, and we forget to talk about blood pressure, which has more than earned its reputation as ‘the silent killer.’ ”

The modeling study was published online  in Nature Medicine, with lead author Sarah J. Pickersgill, MPH, also from the University of Washington.
 

Two interventions, three scenarios

Dr. Watkins and colleagues based their analysis on two approaches to blood pressure (BP) control shown to be beneficial: drug treatment to a systolic BP of either 130 mm Hg or 140 mm Hg or less, depending on local guidelines, and dietary sodium reduction, as recommended by the World Health Organization.

The team modeled the impacts of these interventions in 182 countries according to three scenarios:

• Business as usual (control): allowing hypertension to increase at historic rates of change and mean sodium intake to remain at current levels
• Progress: matching historically high-performing countries (for example, accelerating hypertension control by about 3% per year at intermediate levels of intervention coverage) while lowering mean sodium intake by 15% by 2030
• Aspirational: hypertension control achieved faster than historically high-performing countries (about 4% per year) and mean sodium intake decreased by 30% by 2027

The analysis suggests that in the progressive scenario, all countries could achieve 80-80-80 targets by 2050 and most countries by 2040; the aspirational scenario would have all countries meeting them by 2040. That would result in reductions in all-cause mortality of 4%-7% (76 million to 130 million deaths averted) with progressive and aspirational interventions, respectively, compared with the control scenario.

There would also be a slower rise in expected CVD from population growth and aging (110 million to 200 million cases averted). That is, the probability of dying from any CVD cause between the ages of 30 and 80 years would be reduced by 16% in the progressive scenario and 26% in the aspirational scenario.

Of note, about 83%-85% of the potential mortality reductions would result from scaling up hypertension treatment in the progressive and aspirational scenarios, respectively, with the remaining 15%-17% coming from sodium reduction, the researchers state.

Further, they propose, scaling up BP interventions could reduce CVD inequalities across countries, with low-income and lower-middle-income countries likely experiencing the largest reductions in disease rates and mortality.
 

Implementation barriers

“Health systems in many low- and middle-income countries have not traditionally been set up to succeed in chronic disease management in primary care,” Dr. Watkins noted. For interventions to be successful, he said, “several barriers need to be addressed, including: low population awareness of chronic diseases like hypertension and diabetes, which leads to low rates of screening and treatment; high out-of-pocket cost and low availability of medicines for chronic diseases; and need for adherence support and provider incentives for improving quality of chronic disease care in primary care settings.”

“Based on the analysis, achieving the 80-80-80 seems feasible, though actually getting there may be much more complicated. I wonder whether countries have the resources to implement the needed policies,” Rodrigo M. Carrillo-Larco, MD, researcher, department of epidemiology and biostatistics, School of Public Health, Imperial College London, told this news organization.

“It may be challenging, particularly after COVID-19, which revealed deficiencies in many health care systems, and care for hypertension may have been disturbed,” said Dr. Carrillo-Larco, who is not connected with the analysis.

That said, simplified BP screening approaches could help maximize the number of people screened overall, potentially identifying those with hypertension and raising awareness, he proposed. His team’s recent study showed that such approaches vary from country to country but are generally reliable and can be used effectively for population screening.

In addition, Dr. Carrillo-Larco said, any efforts by clinicians to improve adherence and help patients achieve BP control “would also have positive effects at the population level.”

The study was supported by a grant from the Bill & Melinda Gates Foundation, with additional funding by a grant to Dr. Watkins from Resolve to Save Lives. No conflicts of interest were declared.

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

If 80% of individuals with hypertension were screened, 80% received treatment, and 80% then reached guideline-specified targets, up to 200 million cases of cardiovascular disease (CVD) and 130 million deaths could be averted by 2050, a modeling study suggests.

Achievement of the 80-80-80 target “could be one of the single most important global public health accomplishments of the coming decades,” according to the authors.

“We need to reprioritize hypertension care in our practices,” principal investigator David A. Watkins, MD, MPH, University of Washington, Seattle, told this news organization. “Only about one in five persons with hypertension around the world has their blood pressure well controlled. Oftentimes, clinicians are focused on addressing patients’ other health needs, many of which can be pressing in the short term, and we forget to talk about blood pressure, which has more than earned its reputation as ‘the silent killer.’ ”

The modeling study was published online  in Nature Medicine, with lead author Sarah J. Pickersgill, MPH, also from the University of Washington.
 

Two interventions, three scenarios

Dr. Watkins and colleagues based their analysis on two approaches to blood pressure (BP) control shown to be beneficial: drug treatment to a systolic BP of either 130 mm Hg or 140 mm Hg or less, depending on local guidelines, and dietary sodium reduction, as recommended by the World Health Organization.

The team modeled the impacts of these interventions in 182 countries according to three scenarios:

• Business as usual (control): allowing hypertension to increase at historic rates of change and mean sodium intake to remain at current levels
• Progress: matching historically high-performing countries (for example, accelerating hypertension control by about 3% per year at intermediate levels of intervention coverage) while lowering mean sodium intake by 15% by 2030
• Aspirational: hypertension control achieved faster than historically high-performing countries (about 4% per year) and mean sodium intake decreased by 30% by 2027

The analysis suggests that in the progressive scenario, all countries could achieve 80-80-80 targets by 2050 and most countries by 2040; the aspirational scenario would have all countries meeting them by 2040. That would result in reductions in all-cause mortality of 4%-7% (76 million to 130 million deaths averted) with progressive and aspirational interventions, respectively, compared with the control scenario.

There would also be a slower rise in expected CVD from population growth and aging (110 million to 200 million cases averted). That is, the probability of dying from any CVD cause between the ages of 30 and 80 years would be reduced by 16% in the progressive scenario and 26% in the aspirational scenario.

Of note, about 83%-85% of the potential mortality reductions would result from scaling up hypertension treatment in the progressive and aspirational scenarios, respectively, with the remaining 15%-17% coming from sodium reduction, the researchers state.

Further, they propose, scaling up BP interventions could reduce CVD inequalities across countries, with low-income and lower-middle-income countries likely experiencing the largest reductions in disease rates and mortality.
 

Implementation barriers

“Health systems in many low- and middle-income countries have not traditionally been set up to succeed in chronic disease management in primary care,” Dr. Watkins noted. For interventions to be successful, he said, “several barriers need to be addressed, including: low population awareness of chronic diseases like hypertension and diabetes, which leads to low rates of screening and treatment; high out-of-pocket cost and low availability of medicines for chronic diseases; and need for adherence support and provider incentives for improving quality of chronic disease care in primary care settings.”

“Based on the analysis, achieving the 80-80-80 seems feasible, though actually getting there may be much more complicated. I wonder whether countries have the resources to implement the needed policies,” Rodrigo M. Carrillo-Larco, MD, researcher, department of epidemiology and biostatistics, School of Public Health, Imperial College London, told this news organization.

“It may be challenging, particularly after COVID-19, which revealed deficiencies in many health care systems, and care for hypertension may have been disturbed,” said Dr. Carrillo-Larco, who is not connected with the analysis.

That said, simplified BP screening approaches could help maximize the number of people screened overall, potentially identifying those with hypertension and raising awareness, he proposed. His team’s recent study showed that such approaches vary from country to country but are generally reliable and can be used effectively for population screening.

In addition, Dr. Carrillo-Larco said, any efforts by clinicians to improve adherence and help patients achieve BP control “would also have positive effects at the population level.”

The study was supported by a grant from the Bill & Melinda Gates Foundation, with additional funding by a grant to Dr. Watkins from Resolve to Save Lives. No conflicts of interest were declared.

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