Cardiology

PCSK9 inhibitors, which are among the most effective therapies for reducing LDL cholesterol (LDL-C), are associated with a neutral effect on cognitive function, according to a genetics-based Mendelian randomization study intended to sort out through the complexity of confounders.

The same study linked HMG-Co A reductase inhibitors (statins) with the potential for modest adverse neurocognitive effects, although these are likely to be outweighed by cardiovascular benefits, according to a collaborating team of investigators from the U.S. National Institutes of Health and the University of Oxford (England).

For clinicians and patients who continue to harbor concerns that cognitive function is threatened by very low LDL-C, this novel approach to evaluating risk is “reassuring,” according to the authors.

Early in clinical testing of PCSK9 inhibitors, a potential signal for adverse effects on cognitive function was reported but unconfirmed. This signal raised concern that extremely low levels of LDL-C, such as < 25 mg/dL, achieved with PCSK9 inhibitors might pose a risk to neurocognitive function.

Of several factors that provided a basis for concern, the PCSK9 enzyme is known to participate in brain development, according to the authors of this newly published study.
 

Mendelian randomization addresses complex issue

The objective of this Mendelian randomization analysis was to evaluate the relationship of PCSK9 inhibitors and statins on long-term neurocognitive function. Used previously to address other clinical issues, a drug-effect Mendelian randomization analysis evaluates genetic variants to determine whether there is a causal relationship between a risk, which in this case was lipid-lowering drugs, to a specific outcome, which was cognitive performance.

By looking directly at genetic variants that simulate the pharmacological inhibition of drug gene targets, the bias of confounders of clinical effects, such as baseline cognitive function, are avoided, according to the authors.

The message from this drug-effect Mendelian analysis was simple, according to the senior author of the study, Falk W. Lohoff, MD, chief of the section on clinical genomics and experimental therapeutics, National Institute of Alcohol Abuse and Alcoholism.

“Based on our data, we do not see a significant cognitive risk profile with PCSK9 inhibition associated with low LDL-C,” Dr. Lohoff said in an interview. He cautioned that “future long-term clinical studies are needed to confirm the absence of this effect,” but he and his coauthors noted that these data concur with the clinical studies.

From genome-wide association studies, single-nucleotide polymorphisms in PCSK9 and HMG-Co A reductase were extracted from a sample of more than 700,000 individuals of predominantly European ancestry. In the analysis, the investigators evaluated whether inhibition of PCSK9 or HMG-Co A reductase had an effect on seven clinical outcomes that relate to neurocognitive function, including memory, verbal intelligence, and reaction time, as well as biomarkers of cognitive function, such as cortical surface area.

The genetic effect of PCSK9 inhibition was “null for every cognitive-related outcome evaluated,” the investigators reported. The genetic effect of HMG-Co A reductase inhibition had a statistically significant but modest effect on cognitive performance (P = .03) and cortical surface area (P = .03). While the impact of HMG-Co A reductase inhibition on reaction time was stronger on a statistical basis (P = .0002), the investigators reported that it translated into a decrease of only 0.067 milliseconds per 38.7 mg/dL. They characterized this as a “small impact” unlikely to outweigh clinical benefits.

In an editorial that accompanied publication of this study, Brian A. Ference, MD, MPhil, provided context for the suitability of a Mendelian randomization analysis to address this or other questions regarding the impact of lipid-lowering therapies on clinical outcomes, and he ultimately concurred with the major conclusions

Ultimately, this analysis is consistent with other evidence that PCSK9 inhibition does not pose a risk of impaired cognitive function, he wrote. For statins, he concluded that this study “does not provide compelling evidence” to challenge their current clinical use.


 

Data do not support low LDL-C as cognitive risk factor

Moreover, this study – as well as other evidence – argues strongly against very low levels of LDL-C, regardless of how they are achieved, as a risk factor for diminished cognitive function, Dr. Ference, director of research in the division of translational therapeutics, University of Cambridge (England), said in an interview.

“There is no evidence from Mendelian randomization studies that lifelong exposure to lower LDL-C increases the risk of cognitive impairment,” he said. “This is true when evaluating lifelong exposure to lower LDL-C due to genetic variants in a wide variety of different genes or the genes that encode the target PCKS9 inhibitors, statins, or other lipid-lowering therapies.”

In other words, this study “adds to the accumulating evidence” that LDL-C lowering by itself does not contribute to an adverse impact on cognitive function despite persistent concern. This should not be surprising. Dr. Ference emphasized that there has never been strong evidence for an association.

“As I point out in the editorial, there is no biologically plausible mechanism by which reducing peripheral LDL-C should impact neurological function in any way, because the therapies do not cross the blood brain barrier, and because the nervous system produces its own cholesterol to maintain the integrity of membranes in nervous system cells,” he explained.

Dr. Lohoff reports no potential conflicts of interest. Dr. Ference has financial relationships with numerous pharmaceutical companies including those that make lipid-lowering therapies.

PCSK9 inhibitors, which are among the most effective therapies for reducing LDL cholesterol (LDL-C), are associated with a neutral effect on cognitive function, according to a genetics-based Mendelian randomization study intended to sort out through the complexity of confounders.

The same study linked HMG-Co A reductase inhibitors (statins) with the potential for modest adverse neurocognitive effects, although these are likely to be outweighed by cardiovascular benefits, according to a collaborating team of investigators from the U.S. National Institutes of Health and the University of Oxford (England).

For clinicians and patients who continue to harbor concerns that cognitive function is threatened by very low LDL-C, this novel approach to evaluating risk is “reassuring,” according to the authors.

Early in clinical testing of PCSK9 inhibitors, a potential signal for adverse effects on cognitive function was reported but unconfirmed. This signal raised concern that extremely low levels of LDL-C, such as < 25 mg/dL, achieved with PCSK9 inhibitors might pose a risk to neurocognitive function.

Of several factors that provided a basis for concern, the PCSK9 enzyme is known to participate in brain development, according to the authors of this newly published study.
 

Mendelian randomization addresses complex issue

The objective of this Mendelian randomization analysis was to evaluate the relationship of PCSK9 inhibitors and statins on long-term neurocognitive function. Used previously to address other clinical issues, a drug-effect Mendelian randomization analysis evaluates genetic variants to determine whether there is a causal relationship between a risk, which in this case was lipid-lowering drugs, to a specific outcome, which was cognitive performance.

By looking directly at genetic variants that simulate the pharmacological inhibition of drug gene targets, the bias of confounders of clinical effects, such as baseline cognitive function, are avoided, according to the authors.

The message from this drug-effect Mendelian analysis was simple, according to the senior author of the study, Falk W. Lohoff, MD, chief of the section on clinical genomics and experimental therapeutics, National Institute of Alcohol Abuse and Alcoholism.

“Based on our data, we do not see a significant cognitive risk profile with PCSK9 inhibition associated with low LDL-C,” Dr. Lohoff said in an interview. He cautioned that “future long-term clinical studies are needed to confirm the absence of this effect,” but he and his coauthors noted that these data concur with the clinical studies.

From genome-wide association studies, single-nucleotide polymorphisms in PCSK9 and HMG-Co A reductase were extracted from a sample of more than 700,000 individuals of predominantly European ancestry. In the analysis, the investigators evaluated whether inhibition of PCSK9 or HMG-Co A reductase had an effect on seven clinical outcomes that relate to neurocognitive function, including memory, verbal intelligence, and reaction time, as well as biomarkers of cognitive function, such as cortical surface area.

The genetic effect of PCSK9 inhibition was “null for every cognitive-related outcome evaluated,” the investigators reported. The genetic effect of HMG-Co A reductase inhibition had a statistically significant but modest effect on cognitive performance (P = .03) and cortical surface area (P = .03). While the impact of HMG-Co A reductase inhibition on reaction time was stronger on a statistical basis (P = .0002), the investigators reported that it translated into a decrease of only 0.067 milliseconds per 38.7 mg/dL. They characterized this as a “small impact” unlikely to outweigh clinical benefits.

In an editorial that accompanied publication of this study, Brian A. Ference, MD, MPhil, provided context for the suitability of a Mendelian randomization analysis to address this or other questions regarding the impact of lipid-lowering therapies on clinical outcomes, and he ultimately concurred with the major conclusions

Ultimately, this analysis is consistent with other evidence that PCSK9 inhibition does not pose a risk of impaired cognitive function, he wrote. For statins, he concluded that this study “does not provide compelling evidence” to challenge their current clinical use.


 

Data do not support low LDL-C as cognitive risk factor

Moreover, this study – as well as other evidence – argues strongly against very low levels of LDL-C, regardless of how they are achieved, as a risk factor for diminished cognitive function, Dr. Ference, director of research in the division of translational therapeutics, University of Cambridge (England), said in an interview.

“There is no evidence from Mendelian randomization studies that lifelong exposure to lower LDL-C increases the risk of cognitive impairment,” he said. “This is true when evaluating lifelong exposure to lower LDL-C due to genetic variants in a wide variety of different genes or the genes that encode the target PCKS9 inhibitors, statins, or other lipid-lowering therapies.”

In other words, this study “adds to the accumulating evidence” that LDL-C lowering by itself does not contribute to an adverse impact on cognitive function despite persistent concern. This should not be surprising. Dr. Ference emphasized that there has never been strong evidence for an association.

“As I point out in the editorial, there is no biologically plausible mechanism by which reducing peripheral LDL-C should impact neurological function in any way, because the therapies do not cross the blood brain barrier, and because the nervous system produces its own cholesterol to maintain the integrity of membranes in nervous system cells,” he explained.

Dr. Lohoff reports no potential conflicts of interest. Dr. Ference has financial relationships with numerous pharmaceutical companies including those that make lipid-lowering therapies.

PCSK9 inhibitors, which are among the most effective therapies for reducing LDL cholesterol (LDL-C), are associated with a neutral effect on cognitive function, according to a genetics-based Mendelian randomization study intended to sort out through the complexity of confounders.

The same study linked HMG-Co A reductase inhibitors (statins) with the potential for modest adverse neurocognitive effects, although these are likely to be outweighed by cardiovascular benefits, according to a collaborating team of investigators from the U.S. National Institutes of Health and the University of Oxford (England).

For clinicians and patients who continue to harbor concerns that cognitive function is threatened by very low LDL-C, this novel approach to evaluating risk is “reassuring,” according to the authors.

Early in clinical testing of PCSK9 inhibitors, a potential signal for adverse effects on cognitive function was reported but unconfirmed. This signal raised concern that extremely low levels of LDL-C, such as < 25 mg/dL, achieved with PCSK9 inhibitors might pose a risk to neurocognitive function.

Of several factors that provided a basis for concern, the PCSK9 enzyme is known to participate in brain development, according to the authors of this newly published study.
 

Mendelian randomization addresses complex issue

The objective of this Mendelian randomization analysis was to evaluate the relationship of PCSK9 inhibitors and statins on long-term neurocognitive function. Used previously to address other clinical issues, a drug-effect Mendelian randomization analysis evaluates genetic variants to determine whether there is a causal relationship between a risk, which in this case was lipid-lowering drugs, to a specific outcome, which was cognitive performance.

By looking directly at genetic variants that simulate the pharmacological inhibition of drug gene targets, the bias of confounders of clinical effects, such as baseline cognitive function, are avoided, according to the authors.

The message from this drug-effect Mendelian analysis was simple, according to the senior author of the study, Falk W. Lohoff, MD, chief of the section on clinical genomics and experimental therapeutics, National Institute of Alcohol Abuse and Alcoholism.

“Based on our data, we do not see a significant cognitive risk profile with PCSK9 inhibition associated with low LDL-C,” Dr. Lohoff said in an interview. He cautioned that “future long-term clinical studies are needed to confirm the absence of this effect,” but he and his coauthors noted that these data concur with the clinical studies.

From genome-wide association studies, single-nucleotide polymorphisms in PCSK9 and HMG-Co A reductase were extracted from a sample of more than 700,000 individuals of predominantly European ancestry. In the analysis, the investigators evaluated whether inhibition of PCSK9 or HMG-Co A reductase had an effect on seven clinical outcomes that relate to neurocognitive function, including memory, verbal intelligence, and reaction time, as well as biomarkers of cognitive function, such as cortical surface area.

The genetic effect of PCSK9 inhibition was “null for every cognitive-related outcome evaluated,” the investigators reported. The genetic effect of HMG-Co A reductase inhibition had a statistically significant but modest effect on cognitive performance (P = .03) and cortical surface area (P = .03). While the impact of HMG-Co A reductase inhibition on reaction time was stronger on a statistical basis (P = .0002), the investigators reported that it translated into a decrease of only 0.067 milliseconds per 38.7 mg/dL. They characterized this as a “small impact” unlikely to outweigh clinical benefits.

In an editorial that accompanied publication of this study, Brian A. Ference, MD, MPhil, provided context for the suitability of a Mendelian randomization analysis to address this or other questions regarding the impact of lipid-lowering therapies on clinical outcomes, and he ultimately concurred with the major conclusions

Ultimately, this analysis is consistent with other evidence that PCSK9 inhibition does not pose a risk of impaired cognitive function, he wrote. For statins, he concluded that this study “does not provide compelling evidence” to challenge their current clinical use.


 

Data do not support low LDL-C as cognitive risk factor

Moreover, this study – as well as other evidence – argues strongly against very low levels of LDL-C, regardless of how they are achieved, as a risk factor for diminished cognitive function, Dr. Ference, director of research in the division of translational therapeutics, University of Cambridge (England), said in an interview.

“There is no evidence from Mendelian randomization studies that lifelong exposure to lower LDL-C increases the risk of cognitive impairment,” he said. “This is true when evaluating lifelong exposure to lower LDL-C due to genetic variants in a wide variety of different genes or the genes that encode the target PCKS9 inhibitors, statins, or other lipid-lowering therapies.”

In other words, this study “adds to the accumulating evidence” that LDL-C lowering by itself does not contribute to an adverse impact on cognitive function despite persistent concern. This should not be surprising. Dr. Ference emphasized that there has never been strong evidence for an association.

“As I point out in the editorial, there is no biologically plausible mechanism by which reducing peripheral LDL-C should impact neurological function in any way, because the therapies do not cross the blood brain barrier, and because the nervous system produces its own cholesterol to maintain the integrity of membranes in nervous system cells,” he explained.

Dr. Lohoff reports no potential conflicts of interest. Dr. Ference has financial relationships with numerous pharmaceutical companies including those that make lipid-lowering therapies.

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

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

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

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

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

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

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

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

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

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

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

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

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

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

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

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

Patients who take beta-blockers or antiplatelet agents are lowering their risk for cardiovascular events, but the protection may fall short for those who spend time outdoors on hot summer days, hints a limited analysis published as a letter in Nature Cardiovascular Research.

Patients taking either a beta-blocker or antiplatelet, or both medications together, appeared at elevated risk for nonfatal acute MI specifically on days when the weather turned hot, suggests the registry cohort study that covered 14 years of clinical and meteorologic data.

rottadana/Thinkstock

“The take-away message is not that patients should stop using these two medications, by no means. We’re raising cautions for patients taking them, to watch out for themselves during high-heat days,” lead author Kai Chen, PhD, Yale University, New Haven, Conn., said in an interview.

“We’re not giving the message that these drugs have harmful effects” because the nature of the links between the medications and MI in the study, with its potential for confounding, remain unknown, said Dr. Chen, from the department of environmental health sciences and Yale Center on Climate Change and Health.

For example, patients who take beta-blockers or antiplatelets tend to be sicker than patients not on the drugs, which could make heat-related MI more likely, and the drugs wrongly appear to be culprits, he observed. The analysis contained signals that could support either scenario.

The study is based on cases of nonfatal MI in Augsburg, Germany, that are part of the MONICA-KORA MI registry. The odds of a heat-related nonfatal MI, it suggests, were increased 63% among patients taking antiplatelets and by 65% among those on beta-blockers, compared with those not on these drugs. The odds went up by 75% among those on both drug classes, but the risks weren’t raised in patients not taking them.
 

Rising heat-related MI

Chen said analysis was inspired by a 2019 report – also based on MONICA-KORA, from many of the same authors and using similar methods to track events by daily air temperature – that showed a rising trend for heat-related MI and declining rate for MI related to cold weather from 1987 to 2014. A next step, he figured, would be to determine whether the MI risk trends were associated with any cardiovascular medications.

The current study’s signal of risk related to antiplatelets and beta-blockers did not emerge for ACE inhibitors, calcium-channel blockers, or diuretics. Statins showed a link to increased nonfatal MI risk, but solely among participants aged younger than 60 years, who were also far less likely to have pre-existing coronary heart disease (CHD). He and his colleagues chose not to highlight that finding, Dr. Chen said, because the age subgroup analysis was grossly underpowered.

The overall analysis involved 2,494 cases of nonfatal MI that occurred during the warmer months – May to September – from 2001 to 2014. It was limited to nonfatal cases – those with at least a month of survival after hospital admission – because of insufficient data on medication use associated with fatal MIs, the report states.

Nonfatal MIs were defined as heat-related if they struck on days reaching the 95th percentile for temperature across the 14 years, in this case 24.2 °C (about 75.6 °F), relative to the average temperature of lowest nonfatal MI risk across the cohort, 7.5 °C (about 45.5 °F).

Patients served as both cases and their own controls, in that air temperature exposures on the day of their MI (case day) were compared with the remaining same days of the week in the same calendar month (control days). That approach, the report stated, “automatically controls for long-term time trends, seasonality, day of the week, and time-invariant confounders (for example, pre-existing cardiovascular disease).”

The odds ratio for heat-related MI for patients on antiplatelets was 1.63 (95% confidence interval, 1.07-2.46), and for antiplatelet nonusers was 0.94 (95% CI, 0.68-1.29). The difference between the two ratios was significant (P = .04).

The corresponding OR for patients taking beta-blockers was 1.65 (95% CI, 1.11-2.45), and for nonusers of beta-blockers was 0.90 (95% CI, 0.64-1.26). Again, the OR difference was significant (P = .02).

The ORs for users of both medication classes and nonusers of either med class, respectively, were 1.75 (95% CI, 1.12-2.73) and 0.84 (95% CI, 0.59-1.19). The latter OR was significantly lower than former (P = .01).

In a sign that antiplatelet and beta-blocker use might have been just a marker for sicker patients who were more vulnerable to heat-related MI, Chen said, the nonfatal MI risk was significantly elevated (OR, 2.17; 95% CI, 1.40-3.38) among patients with pre-existing CHD, but not among those free of pre-existing CHD (OR, 0.88; 95% CI, 0.65-1.20); the odds difference was P < .01.

That signal of confounding by indication is somewhat countered, the report states, by variations in nonfatal MI risk by age group. The increased chances of an event seen overall in relation to beta-blockers and antiplatelets were more pronounced among the 39% of patients aged 25-59 years (P < .01). That’s in spite that group’s lower CHD prevalence. The risk elevation solely among the older patients was attenuated and rendered nonsignificant, even with their greater CHD burden, the report noted.

The report speculates on a potential mechanism by which beta-blockers, at least, might conceivably raise the risk for heat-related MI. “Beta-receptor blockers inhibit skin vasodilation, resulting in reduced heat dissipation through convection and, at the same time, could intensify the blood-pressure-lowering effect of other antihypertensive drugs, which then could lead to syncope.”

Beta-blockers, Dr. Chen said, “can mechanistically make people more vulnerable to heat. That’s one potential explanation. Or it could be that these people taking the medications are just sicker. Whatever the reasons, the phenomenon we observed is that these patients taking these two medications are at higher risk during high-temperature days.”

Dr. Chen and the other authors declare no competing interests.

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

Treatment with the novel agent omecamtiv mecarbil did not improve exercise capacity in people with chronic heart failure with reduced ejection fraction (HFrEF), in the METEORIC-HF trial.

The double-blind, phase 3 study failed to achieve its primary endpoint of change in peak oxygen uptake (VO₂) after 20 weeks of treatment with omecamtiv mecarbil, compared with placebo.

There also was no benefit on secondary measures of total workload, ventilatory efficiency, and daily physical activity, according to results presented earlier this year at ACC 2022 and formally published this month in JAMA.

“These findings do not support the use of omecamtiv mecarbil for treatment of HFrEF for improvement of exercise capacity,” lead author Gregory D. Lewis, MD, Massachusetts General Hospital, Boston, and colleagues conclude in the paper.

Researchers had hoped that the oral selective myosin activator would prove useful in this subset of patients, having previously shown in the GALACTIC-HF trial to provide a significant improvement in heart failure (HF) events and cardiovascular death.

A prespecified subgroup analysis from that trial also found that HF patients with the lowest ejection fraction derived the greatest relative benefit from omecamtiv mecarbil.

“The lack of effect of omecamtiv mecarbil on exercise performance is inconsistent with its known mechanism of action of directly enhancing ventricular performance and reducing the risk of cardiovascular events,” Dr. Lewis and colleagues observe.

The drug’s novel mechanism of action, direct activation of myosin, contrasts with that of currently available inotropic agents, such as dobutamine or milrinone. It is not yet approved by the U.S. Food and Drug Administration but is scheduled for an advisory committee meeting on Dec. 13, 2022, and has been assigned a Prescription Drug User Fee Act date of Feb. 28, 2023.

METEORIC-HF randomly assigned 276 patients with New York Heart Association class II or III symptoms and a left ventricular ejection fraction of 35% or less to omecamtiv mecarbil (n = 185) or placebo (n = 91), given orally twice daily at a dose of 25 mg, 37.5 mg, or 50 mg based on target plasma levels for 20 weeks, on top of guideline-directed medical therapy.

The patients’ median age was 64 years and 15% were women. The median ejection fraction was 28% and median baseline peak VO₂ was 14.2 mL/kg per minute in the omecamtiv mecarbil group and 15.0 mL/kg per minute in the control group.

At 20 weeks, the mean change in peak VO₂ in the omecamtiv mecarbil group was –0.24 mL/kg per minute and 0.21 mL/kg per minute in the placebo group (95% confidence interval, –1.02-0.13; P = .13).

For the secondary outcomes, the change in workload achieved on stress testing declined in the omecamtiv mecarbil group (–3.8 vs. 1.6). The drug had a neutral effect on minute ventilation relative to carbon dioxide production throughout exercise (0.28 vs. –0.14 VE/VCO₂ slope) and average total daily activity units, measured over 2 weeks by accelerometer (–0.2 vs. –0.5).

The authors suggest that “one possible explanation for discordance between clinical events in a long-term follow-up study and exercise capacity improvement is that cardiac performance was not exclusively responsible for limiting exercise capacity in trial participants with HFrEF who were stable and very well treated with both pharmacologic and device HFrEF therapy.”

In an accompanying editorial, Mark H. Drazner, MD, MSc, University of Texas Southwestern Medical Center, Dallas, writes that another possible explanation is that participants in METEORIC-HF had less severe heart failure, compared with participants in GALACTIC-HF, and so were less likely to benefit from omecamtiv mecarbil.

METEORIC-HF excluded participants who had a HF hospitalization that required intravenous diuretics in the preceding 3 months, whereas 25% of participants in GALACTIC-HF were inpatients for decompensated HF and 36% had a HF hospitalization within the preceding 3 months.

Another plausible explanation for the differing results is that a therapy that improves long-term clinical outcomes may not improve exercise capacity, Dr. Drazner writes. “The available data are persuasive to suggest this may be the case.”

Some pharmacologic therapies, such as flosequinan, improved exercise capacity in patients with HF yet increased long-term mortality, he noted. Several medications that have a class I recommendation in the 2022 Heart Failure Guideline for the treatment of HFrEF also have not been shown to improve exercise capacity, as measured by peak VO₂ or by 6-minute walk distance.

In this context, Dr. Drazner said he doesn’t anticipate the METEORIC-HF findings to derail FDA approval. However, should the drug be approved, clinicians will have increasingly complex decisions to make about which therapies should be prescribed to which patients.

“Some clinicians may contemplate using omecamtiv mecarbil either in the subgroup of patients with very low ejection fractions or more severe disease, believing this strategy will maximize the benefits of this therapy, but those approaches should be pursued with caution given they are predicated on subgroup and post hoc analyses, respectively,” he wrote.

Dr. Drazner concludes that medications known to improve survival in patients with HFrEF are used at “disappointingly low rates and suboptimal doses in the United States. Implementation strategies to improve use of such therapies are needed, and those efforts should be prioritized before adoption of therapies that reduce morbidity but not cardiovascular mortality.”

The study was sponsored by Amgen and Cytokinetics. Dr. Lewis reports financial relationships with the National Institutes of Health, American Heart Association, Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, SoniVie, Pfizer, Merck, Boehringer Ingelheim, Novartis, American Regent, Cyclerion, MyoKardia, Novo Nordisk, and UpToDate. Dr. Drazner reports being a member of the writing committee of the 2022 Heart Failure guidelines; and that he is supported by the James M. Wooten Chair in Cardiology at the University of Texas Southwestern Medical Center, which was a clinical site in METEORIC-HF. However, Dr. Drazner was not a study investigator in the trial.

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

Treatment with the novel agent omecamtiv mecarbil did not improve exercise capacity in people with chronic heart failure with reduced ejection fraction (HFrEF), in the METEORIC-HF trial.

The double-blind, phase 3 study failed to achieve its primary endpoint of change in peak oxygen uptake (VO₂) after 20 weeks of treatment with omecamtiv mecarbil, compared with placebo.

There also was no benefit on secondary measures of total workload, ventilatory efficiency, and daily physical activity, according to results presented earlier this year at ACC 2022 and formally published this month in JAMA.

“These findings do not support the use of omecamtiv mecarbil for treatment of HFrEF for improvement of exercise capacity,” lead author Gregory D. Lewis, MD, Massachusetts General Hospital, Boston, and colleagues conclude in the paper.

Researchers had hoped that the oral selective myosin activator would prove useful in this subset of patients, having previously shown in the GALACTIC-HF trial to provide a significant improvement in heart failure (HF) events and cardiovascular death.

A prespecified subgroup analysis from that trial also found that HF patients with the lowest ejection fraction derived the greatest relative benefit from omecamtiv mecarbil.

“The lack of effect of omecamtiv mecarbil on exercise performance is inconsistent with its known mechanism of action of directly enhancing ventricular performance and reducing the risk of cardiovascular events,” Dr. Lewis and colleagues observe.

The drug’s novel mechanism of action, direct activation of myosin, contrasts with that of currently available inotropic agents, such as dobutamine or milrinone. It is not yet approved by the U.S. Food and Drug Administration but is scheduled for an advisory committee meeting on Dec. 13, 2022, and has been assigned a Prescription Drug User Fee Act date of Feb. 28, 2023.

METEORIC-HF randomly assigned 276 patients with New York Heart Association class II or III symptoms and a left ventricular ejection fraction of 35% or less to omecamtiv mecarbil (n = 185) or placebo (n = 91), given orally twice daily at a dose of 25 mg, 37.5 mg, or 50 mg based on target plasma levels for 20 weeks, on top of guideline-directed medical therapy.

The patients’ median age was 64 years and 15% were women. The median ejection fraction was 28% and median baseline peak VO₂ was 14.2 mL/kg per minute in the omecamtiv mecarbil group and 15.0 mL/kg per minute in the control group.

At 20 weeks, the mean change in peak VO₂ in the omecamtiv mecarbil group was –0.24 mL/kg per minute and 0.21 mL/kg per minute in the placebo group (95% confidence interval, –1.02-0.13; P = .13).

For the secondary outcomes, the change in workload achieved on stress testing declined in the omecamtiv mecarbil group (–3.8 vs. 1.6). The drug had a neutral effect on minute ventilation relative to carbon dioxide production throughout exercise (0.28 vs. –0.14 VE/VCO₂ slope) and average total daily activity units, measured over 2 weeks by accelerometer (–0.2 vs. –0.5).

The authors suggest that “one possible explanation for discordance between clinical events in a long-term follow-up study and exercise capacity improvement is that cardiac performance was not exclusively responsible for limiting exercise capacity in trial participants with HFrEF who were stable and very well treated with both pharmacologic and device HFrEF therapy.”

In an accompanying editorial, Mark H. Drazner, MD, MSc, University of Texas Southwestern Medical Center, Dallas, writes that another possible explanation is that participants in METEORIC-HF had less severe heart failure, compared with participants in GALACTIC-HF, and so were less likely to benefit from omecamtiv mecarbil.

METEORIC-HF excluded participants who had a HF hospitalization that required intravenous diuretics in the preceding 3 months, whereas 25% of participants in GALACTIC-HF were inpatients for decompensated HF and 36% had a HF hospitalization within the preceding 3 months.

Another plausible explanation for the differing results is that a therapy that improves long-term clinical outcomes may not improve exercise capacity, Dr. Drazner writes. “The available data are persuasive to suggest this may be the case.”

Some pharmacologic therapies, such as flosequinan, improved exercise capacity in patients with HF yet increased long-term mortality, he noted. Several medications that have a class I recommendation in the 2022 Heart Failure Guideline for the treatment of HFrEF also have not been shown to improve exercise capacity, as measured by peak VO₂ or by 6-minute walk distance.

In this context, Dr. Drazner said he doesn’t anticipate the METEORIC-HF findings to derail FDA approval. However, should the drug be approved, clinicians will have increasingly complex decisions to make about which therapies should be prescribed to which patients.

“Some clinicians may contemplate using omecamtiv mecarbil either in the subgroup of patients with very low ejection fractions or more severe disease, believing this strategy will maximize the benefits of this therapy, but those approaches should be pursued with caution given they are predicated on subgroup and post hoc analyses, respectively,” he wrote.

Dr. Drazner concludes that medications known to improve survival in patients with HFrEF are used at “disappointingly low rates and suboptimal doses in the United States. Implementation strategies to improve use of such therapies are needed, and those efforts should be prioritized before adoption of therapies that reduce morbidity but not cardiovascular mortality.”

The study was sponsored by Amgen and Cytokinetics. Dr. Lewis reports financial relationships with the National Institutes of Health, American Heart Association, Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, SoniVie, Pfizer, Merck, Boehringer Ingelheim, Novartis, American Regent, Cyclerion, MyoKardia, Novo Nordisk, and UpToDate. Dr. Drazner reports being a member of the writing committee of the 2022 Heart Failure guidelines; and that he is supported by the James M. Wooten Chair in Cardiology at the University of Texas Southwestern Medical Center, which was a clinical site in METEORIC-HF. However, Dr. Drazner was not a study investigator in the trial.

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

Treatment with the novel agent omecamtiv mecarbil did not improve exercise capacity in people with chronic heart failure with reduced ejection fraction (HFrEF), in the METEORIC-HF trial.

The double-blind, phase 3 study failed to achieve its primary endpoint of change in peak oxygen uptake (VO₂) after 20 weeks of treatment with omecamtiv mecarbil, compared with placebo.

There also was no benefit on secondary measures of total workload, ventilatory efficiency, and daily physical activity, according to results presented earlier this year at ACC 2022 and formally published this month in JAMA.

“These findings do not support the use of omecamtiv mecarbil for treatment of HFrEF for improvement of exercise capacity,” lead author Gregory D. Lewis, MD, Massachusetts General Hospital, Boston, and colleagues conclude in the paper.

Researchers had hoped that the oral selective myosin activator would prove useful in this subset of patients, having previously shown in the GALACTIC-HF trial to provide a significant improvement in heart failure (HF) events and cardiovascular death.

A prespecified subgroup analysis from that trial also found that HF patients with the lowest ejection fraction derived the greatest relative benefit from omecamtiv mecarbil.

“The lack of effect of omecamtiv mecarbil on exercise performance is inconsistent with its known mechanism of action of directly enhancing ventricular performance and reducing the risk of cardiovascular events,” Dr. Lewis and colleagues observe.

The drug’s novel mechanism of action, direct activation of myosin, contrasts with that of currently available inotropic agents, such as dobutamine or milrinone. It is not yet approved by the U.S. Food and Drug Administration but is scheduled for an advisory committee meeting on Dec. 13, 2022, and has been assigned a Prescription Drug User Fee Act date of Feb. 28, 2023.

METEORIC-HF randomly assigned 276 patients with New York Heart Association class II or III symptoms and a left ventricular ejection fraction of 35% or less to omecamtiv mecarbil (n = 185) or placebo (n = 91), given orally twice daily at a dose of 25 mg, 37.5 mg, or 50 mg based on target plasma levels for 20 weeks, on top of guideline-directed medical therapy.

The patients’ median age was 64 years and 15% were women. The median ejection fraction was 28% and median baseline peak VO₂ was 14.2 mL/kg per minute in the omecamtiv mecarbil group and 15.0 mL/kg per minute in the control group.

At 20 weeks, the mean change in peak VO₂ in the omecamtiv mecarbil group was –0.24 mL/kg per minute and 0.21 mL/kg per minute in the placebo group (95% confidence interval, –1.02-0.13; P = .13).

For the secondary outcomes, the change in workload achieved on stress testing declined in the omecamtiv mecarbil group (–3.8 vs. 1.6). The drug had a neutral effect on minute ventilation relative to carbon dioxide production throughout exercise (0.28 vs. –0.14 VE/VCO₂ slope) and average total daily activity units, measured over 2 weeks by accelerometer (–0.2 vs. –0.5).

The authors suggest that “one possible explanation for discordance between clinical events in a long-term follow-up study and exercise capacity improvement is that cardiac performance was not exclusively responsible for limiting exercise capacity in trial participants with HFrEF who were stable and very well treated with both pharmacologic and device HFrEF therapy.”

In an accompanying editorial, Mark H. Drazner, MD, MSc, University of Texas Southwestern Medical Center, Dallas, writes that another possible explanation is that participants in METEORIC-HF had less severe heart failure, compared with participants in GALACTIC-HF, and so were less likely to benefit from omecamtiv mecarbil.

METEORIC-HF excluded participants who had a HF hospitalization that required intravenous diuretics in the preceding 3 months, whereas 25% of participants in GALACTIC-HF were inpatients for decompensated HF and 36% had a HF hospitalization within the preceding 3 months.

Another plausible explanation for the differing results is that a therapy that improves long-term clinical outcomes may not improve exercise capacity, Dr. Drazner writes. “The available data are persuasive to suggest this may be the case.”

Some pharmacologic therapies, such as flosequinan, improved exercise capacity in patients with HF yet increased long-term mortality, he noted. Several medications that have a class I recommendation in the 2022 Heart Failure Guideline for the treatment of HFrEF also have not been shown to improve exercise capacity, as measured by peak VO₂ or by 6-minute walk distance.

In this context, Dr. Drazner said he doesn’t anticipate the METEORIC-HF findings to derail FDA approval. However, should the drug be approved, clinicians will have increasingly complex decisions to make about which therapies should be prescribed to which patients.

“Some clinicians may contemplate using omecamtiv mecarbil either in the subgroup of patients with very low ejection fractions or more severe disease, believing this strategy will maximize the benefits of this therapy, but those approaches should be pursued with caution given they are predicated on subgroup and post hoc analyses, respectively,” he wrote.

Dr. Drazner concludes that medications known to improve survival in patients with HFrEF are used at “disappointingly low rates and suboptimal doses in the United States. Implementation strategies to improve use of such therapies are needed, and those efforts should be prioritized before adoption of therapies that reduce morbidity but not cardiovascular mortality.”

The study was sponsored by Amgen and Cytokinetics. Dr. Lewis reports financial relationships with the National Institutes of Health, American Heart Association, Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, SoniVie, Pfizer, Merck, Boehringer Ingelheim, Novartis, American Regent, Cyclerion, MyoKardia, Novo Nordisk, and UpToDate. Dr. Drazner reports being a member of the writing committee of the 2022 Heart Failure guidelines; and that he is supported by the James M. Wooten Chair in Cardiology at the University of Texas Southwestern Medical Center, which was a clinical site in METEORIC-HF. However, Dr. Drazner was not a study investigator in the trial.

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

Black and Hispanic adults are diagnosed with hypertension at a significantly younger age than are white adults, and they also are more likely than Whites to be unaware of undiagnosed high blood pressure, based on national survey data collected from 2011 to 2020.

“Earlier hypertension onset in Black and Hispanic adults may contribute to racial and ethnic CVD disparities,” Xiaoning Huang, PhD, and associates wrote in JAMA Cardiology, also noting that “lower hypertension awareness among racial and ethnic minoritized groups suggests potential for underestimating differences in age at onset.”

Overall mean age at diagnosis was 46 years for the overall study sample of 9,627 participants in the National Health and Nutrition Examination Surveys over the 10 years covered in the analysis. Black adults, with a median age of 42 years, and Hispanic adults (median, 43 years) were significantly younger at diagnosis than White adults, who had a median age of 47 years, the investigators reported.

“Earlier age at hypertension onset may mean greater cumulative exposure to high blood pressure across the life course, which is associated with increased risk of [cardiovascular disease] and may contribute to racial disparities in hypertension-related outcomes,” said Dr. Huang and associates at Northwestern University, Chicago.

The increased cumulative exposure can be seen when age at diagnosis is stratified “across the life course.” Black/Hispanic adults were significantly more likely than White/Asian adults to be diagnosed at or before 30 years of age, and that difference continued to at least age 50 years, the investigators said.

Many adults unaware of their hypertension

There was a somewhat different trend among those in the study population who reported BP at or above 140/90 mm Hg but did not report a hypertension diagnosis. Black, Hispanic, and Asian adults all were significantly more likely than White adults to be unaware of their hypertension, the survey data showed.

Overall, 18% of those who did not report a hypertension diagnosis had a BP of 140/90 mm Hg or higher and 38% had a BP of 130/80 mm Hg or more. Broken down by race and ethnicity, 16% and 36% of Whites reporting no hypertension had BPs of 140/90 and 130/80 mm Hg, respectively; those proportions were 21% and 42% for Hispanics, 24% and 44% for Asians, and 28% and 51% for Blacks, with all of the differences between Whites and the others significant, the research team reported.

One investigator is an associate editor for JAMA Cardiology and reported receiving grants from the American Heart Association and the National Institutes of Health during the conduct of the study. None of the other investigators reported any conflicts.

Black and Hispanic adults are diagnosed with hypertension at a significantly younger age than are white adults, and they also are more likely than Whites to be unaware of undiagnosed high blood pressure, based on national survey data collected from 2011 to 2020.

“Earlier hypertension onset in Black and Hispanic adults may contribute to racial and ethnic CVD disparities,” Xiaoning Huang, PhD, and associates wrote in JAMA Cardiology, also noting that “lower hypertension awareness among racial and ethnic minoritized groups suggests potential for underestimating differences in age at onset.”

Overall mean age at diagnosis was 46 years for the overall study sample of 9,627 participants in the National Health and Nutrition Examination Surveys over the 10 years covered in the analysis. Black adults, with a median age of 42 years, and Hispanic adults (median, 43 years) were significantly younger at diagnosis than White adults, who had a median age of 47 years, the investigators reported.

“Earlier age at hypertension onset may mean greater cumulative exposure to high blood pressure across the life course, which is associated with increased risk of [cardiovascular disease] and may contribute to racial disparities in hypertension-related outcomes,” said Dr. Huang and associates at Northwestern University, Chicago.

The increased cumulative exposure can be seen when age at diagnosis is stratified “across the life course.” Black/Hispanic adults were significantly more likely than White/Asian adults to be diagnosed at or before 30 years of age, and that difference continued to at least age 50 years, the investigators said.

Many adults unaware of their hypertension

There was a somewhat different trend among those in the study population who reported BP at or above 140/90 mm Hg but did not report a hypertension diagnosis. Black, Hispanic, and Asian adults all were significantly more likely than White adults to be unaware of their hypertension, the survey data showed.

Overall, 18% of those who did not report a hypertension diagnosis had a BP of 140/90 mm Hg or higher and 38% had a BP of 130/80 mm Hg or more. Broken down by race and ethnicity, 16% and 36% of Whites reporting no hypertension had BPs of 140/90 and 130/80 mm Hg, respectively; those proportions were 21% and 42% for Hispanics, 24% and 44% for Asians, and 28% and 51% for Blacks, with all of the differences between Whites and the others significant, the research team reported.

One investigator is an associate editor for JAMA Cardiology and reported receiving grants from the American Heart Association and the National Institutes of Health during the conduct of the study. None of the other investigators reported any conflicts.

Black and Hispanic adults are diagnosed with hypertension at a significantly younger age than are white adults, and they also are more likely than Whites to be unaware of undiagnosed high blood pressure, based on national survey data collected from 2011 to 2020.

“Earlier hypertension onset in Black and Hispanic adults may contribute to racial and ethnic CVD disparities,” Xiaoning Huang, PhD, and associates wrote in JAMA Cardiology, also noting that “lower hypertension awareness among racial and ethnic minoritized groups suggests potential for underestimating differences in age at onset.”

Overall mean age at diagnosis was 46 years for the overall study sample of 9,627 participants in the National Health and Nutrition Examination Surveys over the 10 years covered in the analysis. Black adults, with a median age of 42 years, and Hispanic adults (median, 43 years) were significantly younger at diagnosis than White adults, who had a median age of 47 years, the investigators reported.

“Earlier age at hypertension onset may mean greater cumulative exposure to high blood pressure across the life course, which is associated with increased risk of [cardiovascular disease] and may contribute to racial disparities in hypertension-related outcomes,” said Dr. Huang and associates at Northwestern University, Chicago.

The increased cumulative exposure can be seen when age at diagnosis is stratified “across the life course.” Black/Hispanic adults were significantly more likely than White/Asian adults to be diagnosed at or before 30 years of age, and that difference continued to at least age 50 years, the investigators said.

Many adults unaware of their hypertension

There was a somewhat different trend among those in the study population who reported BP at or above 140/90 mm Hg but did not report a hypertension diagnosis. Black, Hispanic, and Asian adults all were significantly more likely than White adults to be unaware of their hypertension, the survey data showed.

Overall, 18% of those who did not report a hypertension diagnosis had a BP of 140/90 mm Hg or higher and 38% had a BP of 130/80 mm Hg or more. Broken down by race and ethnicity, 16% and 36% of Whites reporting no hypertension had BPs of 140/90 and 130/80 mm Hg, respectively; those proportions were 21% and 42% for Hispanics, 24% and 44% for Asians, and 28% and 51% for Blacks, with all of the differences between Whites and the others significant, the research team reported.

One investigator is an associate editor for JAMA Cardiology and reported receiving grants from the American Heart Association and the National Institutes of Health during the conduct of the study. None of the other investigators reported any conflicts.

Researchers from the Centers for Disease Control and Prevention report that children and teenagers with long COVID have about twice the risk of getting serious outcomes, compared to others without COVID.

Heart inflammation; a blood clot in the lung; or a blood clot in the lower leg, thigh, or pelvis were the most common bad outcomes in a new study. Even though the risk was higher for these and some other serious events, the overall numbers were small.

“Many of these conditions were rare or uncommon among children in this analysis, but even a small increase in these conditions is notable,” a CDC new release stated.

The investigators said their findings stress the importance of COVID-19 vaccination in Americans under the age of 18.

The study was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Less is known about long COVID in children

Lyudmyla Kompaniyets, PhD, and colleagues noted that most research on long COVID to date has been done in adults, so little information is available about the risks to Americans ages 17 and younger.

To learn more, they compared post–COVID-19 symptoms and conditions between 781,419 children and teenagers with confirmed COVID-19 to another 2,344,257 without COVID-19. They looked at medical claims and laboratory data for these children and teenagers from March 1, 2020, through Jan. 31, 2022, to see who got any of 15 specific outcomes linked to long COVID-19.

Long COVID was defined as a condition where symptoms that last for or begin at least 4 weeks after a COVID-19 diagnosis.

Compared to children with no history of a COVID-19 diagnosis, the long COVID-19 group was 101% more likely to have an acute pulmonary embolism, 99% more likely to have myocarditis or cardiomyopathy, 87% more likely to have a venous thromboembolic event, 32% more likely to have acute and unspecified renal failure, and 23% more likely to have type 1 diabetes.

“This report points to the fact that the risks of COVID infection itself, both in terms of the acute effects, MIS-C [multisystem inflammatory syndrome in children], as well as the long-term effects, are real, are concerning, and are potentially very serious,” said Stuart Berger, MD, chair of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.

“The message that we should take away from this is that we should be very keen on all the methods of prevention for COVID, especially the vaccine,” said Dr. Berger, chief of cardiology in the department of pediatrics at Northwestern University in Chicago.


 

A ‘wake-up call’

The study findings are “sobering” and are “a reminder of the seriousness of COVID infection,” says Gregory Poland, MD, an infectious disease expert at the Mayo Clinic in Rochester, Minn.

“When you look in particular at the more serious complications from COVID in this young age group, those are life-altering complications that will have consequences and ramifications throughout their lives,” he said.

“I would take this as a serious wake-up call to parents [at a time when] the immunization rates in younger children are so pitifully low,” Dr. Poland said.
 

Still early days

The study is suggestive but not definitive, said Peter Katona, MD, professor of medicine and infectious diseases expert at the UCLA Fielding School of Public Health.

It’s still too early to draw conclusions about long COVID, including in children, because many questions remain, he said: Should long COVID be defined as symptoms at 1 month or 3 months after infection? How do you define brain fog?

Dr. Katona and colleagues are studying long COVID intervention among students at UCLA to answer some of these questions, including the incidence and effect of early intervention.

The study had “at least seven limitations,” the researchers noted. Among them was the use of medical claims data that noted long COVID outcomes but not how severe they were; some people in the no COVID group might have had the illness but not been diagnosed; and the researchers did not adjust for vaccination status.

Dr. Poland noted that the study was done during surges in COVID variants including Delta and Omicron. In other words, any long COVID effects linked to more recent variants such as BA.5 or BA.2.75 are unknown.

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

Researchers from the Centers for Disease Control and Prevention report that children and teenagers with long COVID have about twice the risk of getting serious outcomes, compared to others without COVID.

Heart inflammation; a blood clot in the lung; or a blood clot in the lower leg, thigh, or pelvis were the most common bad outcomes in a new study. Even though the risk was higher for these and some other serious events, the overall numbers were small.

“Many of these conditions were rare or uncommon among children in this analysis, but even a small increase in these conditions is notable,” a CDC new release stated.

The investigators said their findings stress the importance of COVID-19 vaccination in Americans under the age of 18.

The study was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Less is known about long COVID in children

Lyudmyla Kompaniyets, PhD, and colleagues noted that most research on long COVID to date has been done in adults, so little information is available about the risks to Americans ages 17 and younger.

To learn more, they compared post–COVID-19 symptoms and conditions between 781,419 children and teenagers with confirmed COVID-19 to another 2,344,257 without COVID-19. They looked at medical claims and laboratory data for these children and teenagers from March 1, 2020, through Jan. 31, 2022, to see who got any of 15 specific outcomes linked to long COVID-19.

Long COVID was defined as a condition where symptoms that last for or begin at least 4 weeks after a COVID-19 diagnosis.

Compared to children with no history of a COVID-19 diagnosis, the long COVID-19 group was 101% more likely to have an acute pulmonary embolism, 99% more likely to have myocarditis or cardiomyopathy, 87% more likely to have a venous thromboembolic event, 32% more likely to have acute and unspecified renal failure, and 23% more likely to have type 1 diabetes.

“This report points to the fact that the risks of COVID infection itself, both in terms of the acute effects, MIS-C [multisystem inflammatory syndrome in children], as well as the long-term effects, are real, are concerning, and are potentially very serious,” said Stuart Berger, MD, chair of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.

“The message that we should take away from this is that we should be very keen on all the methods of prevention for COVID, especially the vaccine,” said Dr. Berger, chief of cardiology in the department of pediatrics at Northwestern University in Chicago.


 

A ‘wake-up call’

The study findings are “sobering” and are “a reminder of the seriousness of COVID infection,” says Gregory Poland, MD, an infectious disease expert at the Mayo Clinic in Rochester, Minn.

“When you look in particular at the more serious complications from COVID in this young age group, those are life-altering complications that will have consequences and ramifications throughout their lives,” he said.

“I would take this as a serious wake-up call to parents [at a time when] the immunization rates in younger children are so pitifully low,” Dr. Poland said.
 

Still early days

The study is suggestive but not definitive, said Peter Katona, MD, professor of medicine and infectious diseases expert at the UCLA Fielding School of Public Health.

It’s still too early to draw conclusions about long COVID, including in children, because many questions remain, he said: Should long COVID be defined as symptoms at 1 month or 3 months after infection? How do you define brain fog?

Dr. Katona and colleagues are studying long COVID intervention among students at UCLA to answer some of these questions, including the incidence and effect of early intervention.

The study had “at least seven limitations,” the researchers noted. Among them was the use of medical claims data that noted long COVID outcomes but not how severe they were; some people in the no COVID group might have had the illness but not been diagnosed; and the researchers did not adjust for vaccination status.

Dr. Poland noted that the study was done during surges in COVID variants including Delta and Omicron. In other words, any long COVID effects linked to more recent variants such as BA.5 or BA.2.75 are unknown.

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

Researchers from the Centers for Disease Control and Prevention report that children and teenagers with long COVID have about twice the risk of getting serious outcomes, compared to others without COVID.

Heart inflammation; a blood clot in the lung; or a blood clot in the lower leg, thigh, or pelvis were the most common bad outcomes in a new study. Even though the risk was higher for these and some other serious events, the overall numbers were small.

“Many of these conditions were rare or uncommon among children in this analysis, but even a small increase in these conditions is notable,” a CDC new release stated.

The investigators said their findings stress the importance of COVID-19 vaccination in Americans under the age of 18.

The study was published online in the CDC’s Morbidity and Mortality Weekly Report.
 

Less is known about long COVID in children

Lyudmyla Kompaniyets, PhD, and colleagues noted that most research on long COVID to date has been done in adults, so little information is available about the risks to Americans ages 17 and younger.

To learn more, they compared post–COVID-19 symptoms and conditions between 781,419 children and teenagers with confirmed COVID-19 to another 2,344,257 without COVID-19. They looked at medical claims and laboratory data for these children and teenagers from March 1, 2020, through Jan. 31, 2022, to see who got any of 15 specific outcomes linked to long COVID-19.

Long COVID was defined as a condition where symptoms that last for or begin at least 4 weeks after a COVID-19 diagnosis.

Compared to children with no history of a COVID-19 diagnosis, the long COVID-19 group was 101% more likely to have an acute pulmonary embolism, 99% more likely to have myocarditis or cardiomyopathy, 87% more likely to have a venous thromboembolic event, 32% more likely to have acute and unspecified renal failure, and 23% more likely to have type 1 diabetes.

“This report points to the fact that the risks of COVID infection itself, both in terms of the acute effects, MIS-C [multisystem inflammatory syndrome in children], as well as the long-term effects, are real, are concerning, and are potentially very serious,” said Stuart Berger, MD, chair of the American Academy of Pediatrics Section on Cardiology and Cardiac Surgery.

“The message that we should take away from this is that we should be very keen on all the methods of prevention for COVID, especially the vaccine,” said Dr. Berger, chief of cardiology in the department of pediatrics at Northwestern University in Chicago.


 

A ‘wake-up call’

The study findings are “sobering” and are “a reminder of the seriousness of COVID infection,” says Gregory Poland, MD, an infectious disease expert at the Mayo Clinic in Rochester, Minn.

“When you look in particular at the more serious complications from COVID in this young age group, those are life-altering complications that will have consequences and ramifications throughout their lives,” he said.

“I would take this as a serious wake-up call to parents [at a time when] the immunization rates in younger children are so pitifully low,” Dr. Poland said.
 

Still early days

The study is suggestive but not definitive, said Peter Katona, MD, professor of medicine and infectious diseases expert at the UCLA Fielding School of Public Health.

It’s still too early to draw conclusions about long COVID, including in children, because many questions remain, he said: Should long COVID be defined as symptoms at 1 month or 3 months after infection? How do you define brain fog?

Dr. Katona and colleagues are studying long COVID intervention among students at UCLA to answer some of these questions, including the incidence and effect of early intervention.

The study had “at least seven limitations,” the researchers noted. Among them was the use of medical claims data that noted long COVID outcomes but not how severe they were; some people in the no COVID group might have had the illness but not been diagnosed; and the researchers did not adjust for vaccination status.

Dr. Poland noted that the study was done during surges in COVID variants including Delta and Omicron. In other words, any long COVID effects linked to more recent variants such as BA.5 or BA.2.75 are unknown.

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

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

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

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

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

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

From Memora Health (Dr. Flyckt and Dr. Colbert), San Francisco, CA; and Harvard Medical School (Dr. Colbert), Boston, MA.

A close relative was recently diagnosed with follicular lymphoma. He was cared for at a high-ranked cancer center by physicians with demonstrated expertise, and even had the support of a care navigator. Still, he was often left feeling overwhelmed and confused, holding an inch-thick stack of papers, instructions, and pamphlets. As he left his treatment planning visit, reeling from the emotional burden of his diagnosis and all the unfamiliar terminology, he didn’t know what to do or what to expect. Later, when he experienced early signs of tumor lysis syndrome, he struggled to reach his care team for triage and guidance. When he went to the emergency room, his oncologist was never informed.

This scenario is unfortunately common, and versions of this scenario play out thousands of times each day across the US health system. Within the clinic and hospital setting, patients receive excellent care from their providers, but a disconnect emerges once the patient leaves these medical settings: patients at home struggle to find guidance and support, while care teams lack the tools to engage patients between visits or monitor their health across care settings, providers, or episodes of care.

Leveraging Technology to Move From Episodes of Care to Complex Care Journeys

The use of automated messaging, artificial intelligence and natural language processing–driven chat experiences, and text-based support is becoming more common. However, health care lags behind other industries in the adoption of these technologies.^1,2 The slow pace can be warranted, given that health care is more complicated and higher risk than inquiring about a lost package, ordering groceries, or applying for a mortgage. At the same time, many of the consumer engagement tools used to guide an applicant through the multiple steps and complexities of their home loan process or to prompt viewers to select new shows to binge have applications in health care.

Over the past few years, technologies have emerged that guide patients through complex care journeys and allow care teams to monitor and engage patients between visits. These solutions come in different formats, but generally patients can receive messages on their phones that contain disease-specific educational content, prompts to fill prescriptions and take medications, and reminders and guidance on how to prepare for appointments and procedures. These programs also collect relevant data from patients through survey and electronic patient-reported outcomes instruments, as well as connected patient monitoring devices, that help track patient progress and identify issues as they arise. Many programs also incorporate symptom triage pathways and use natural language processing to respond automatically to patient questions and concerns.^3,4

These technology solutions can automate many tasks that in the past required a care team member to spend hours on the phone. Newly freed from such repetitive tasks, care teams can now focus on more in-depth interactions with those patients who are most in need—the types of interactions that are more satisfying and rewarding. Such assistance is particularly needed today with the staffing shortages faced by most health systems.⁵

In addition, technology allows teams to see the panel of patients they are caring for and to quickly identify and take action on any specific needs or issues. Care teams can focus on any patient and see where they are in their journey. When appropriate, some solutions also allow care teams to engage directly with patients through text-messaging, creating a seamless experience and unified communication channel. Ideally, these solutions should be linked or embedded within the electronic health record or other primary system of record, so that teams can easily access these tools through their existing workflows and avoid creating yet another interface to navigate.

The Impact of Low-Tech Solutions to Deliver High-Touch Support

There is evidence showing that digital patient navigation tools impact patient care. In the oncology setting, patients with a digital navigator have achieved over 95% adherence rates with complex oral chemotherapy regimens (Memora Health Unpublished Data. 2022.). In the postpartum setting, a text message–based program improved screening rates for postpartum depression and did so with very high patient satisfaction ratings.⁶ Particularly notable is the fact that this depression screening program achieved these results in a population that was predominantly low income, with more than half belonging to underrepresented minority populations.⁶

We believe these digital patient navigation technologies, specifically low-tech solutions that don’t require app downloads, portal log-ins, or high-speed internet, will transform care delivery over the next 5 to 10 years. Successful management of complex conditions like diabetes or cancer requires more than 3 hours of care each day,⁷ yet most patients spend only 1 or 2 hours per month directly interacting with their health care providers. However, most patients carry their phones with them at all times, and artificial intelligence–enabled text support is “always on” to provide support, monitoring, and guidance, wherever a patient happens to be when assistance is needed.

Shifting the Model to Support a Lifetime of Care

While still in the early stages of development, these tools have the potential to radically alter the practice of medicine, shifting the focus from episodic interactions to continuous journey-based care delivery. Outside of an acute event bringing a patient into the clinic or emergency room, many patients go a year or more without seeing their primary care providers.⁸ During that time, an immense amount of information is underreported or completely lost. Capturing this information in real-time and more holistically over a person’s lifetime of care could provide physicians better insight to both better manage and more fully evaluate the success of treatment plans by tracking patient symptoms, pain, and functional status over time. With this more longitudinal view of the patient, we see a pathway towards achieving the Quadruple Aim: patients who are more supported will achieve better outcomes at lower cost, they will have a better experience, and care teams will be empowered to focus their time on more satisfying activities rather than repetitive administrative tasks.

Corresponding author: James A. Colbert, MD, MBA; [email protected]

Disclosures: Dr. Flyckt and Dr. Colbert are employed by Memora Health, an organization that helps health care systems digitize and automate care journeys.

From Memora Health (Dr. Flyckt and Dr. Colbert), San Francisco, CA; and Harvard Medical School (Dr. Colbert), Boston, MA.

A close relative was recently diagnosed with follicular lymphoma. He was cared for at a high-ranked cancer center by physicians with demonstrated expertise, and even had the support of a care navigator. Still, he was often left feeling overwhelmed and confused, holding an inch-thick stack of papers, instructions, and pamphlets. As he left his treatment planning visit, reeling from the emotional burden of his diagnosis and all the unfamiliar terminology, he didn’t know what to do or what to expect. Later, when he experienced early signs of tumor lysis syndrome, he struggled to reach his care team for triage and guidance. When he went to the emergency room, his oncologist was never informed.

This scenario is unfortunately common, and versions of this scenario play out thousands of times each day across the US health system. Within the clinic and hospital setting, patients receive excellent care from their providers, but a disconnect emerges once the patient leaves these medical settings: patients at home struggle to find guidance and support, while care teams lack the tools to engage patients between visits or monitor their health across care settings, providers, or episodes of care.

Leveraging Technology to Move From Episodes of Care to Complex Care Journeys

The use of automated messaging, artificial intelligence and natural language processing–driven chat experiences, and text-based support is becoming more common. However, health care lags behind other industries in the adoption of these technologies.^1,2 The slow pace can be warranted, given that health care is more complicated and higher risk than inquiring about a lost package, ordering groceries, or applying for a mortgage. At the same time, many of the consumer engagement tools used to guide an applicant through the multiple steps and complexities of their home loan process or to prompt viewers to select new shows to binge have applications in health care.

Over the past few years, technologies have emerged that guide patients through complex care journeys and allow care teams to monitor and engage patients between visits. These solutions come in different formats, but generally patients can receive messages on their phones that contain disease-specific educational content, prompts to fill prescriptions and take medications, and reminders and guidance on how to prepare for appointments and procedures. These programs also collect relevant data from patients through survey and electronic patient-reported outcomes instruments, as well as connected patient monitoring devices, that help track patient progress and identify issues as they arise. Many programs also incorporate symptom triage pathways and use natural language processing to respond automatically to patient questions and concerns.^3,4

These technology solutions can automate many tasks that in the past required a care team member to spend hours on the phone. Newly freed from such repetitive tasks, care teams can now focus on more in-depth interactions with those patients who are most in need—the types of interactions that are more satisfying and rewarding. Such assistance is particularly needed today with the staffing shortages faced by most health systems.⁵

In addition, technology allows teams to see the panel of patients they are caring for and to quickly identify and take action on any specific needs or issues. Care teams can focus on any patient and see where they are in their journey. When appropriate, some solutions also allow care teams to engage directly with patients through text-messaging, creating a seamless experience and unified communication channel. Ideally, these solutions should be linked or embedded within the electronic health record or other primary system of record, so that teams can easily access these tools through their existing workflows and avoid creating yet another interface to navigate.

The Impact of Low-Tech Solutions to Deliver High-Touch Support

There is evidence showing that digital patient navigation tools impact patient care. In the oncology setting, patients with a digital navigator have achieved over 95% adherence rates with complex oral chemotherapy regimens (Memora Health Unpublished Data. 2022.). In the postpartum setting, a text message–based program improved screening rates for postpartum depression and did so with very high patient satisfaction ratings.⁶ Particularly notable is the fact that this depression screening program achieved these results in a population that was predominantly low income, with more than half belonging to underrepresented minority populations.⁶

We believe these digital patient navigation technologies, specifically low-tech solutions that don’t require app downloads, portal log-ins, or high-speed internet, will transform care delivery over the next 5 to 10 years. Successful management of complex conditions like diabetes or cancer requires more than 3 hours of care each day,⁷ yet most patients spend only 1 or 2 hours per month directly interacting with their health care providers. However, most patients carry their phones with them at all times, and artificial intelligence–enabled text support is “always on” to provide support, monitoring, and guidance, wherever a patient happens to be when assistance is needed.

Shifting the Model to Support a Lifetime of Care

While still in the early stages of development, these tools have the potential to radically alter the practice of medicine, shifting the focus from episodic interactions to continuous journey-based care delivery. Outside of an acute event bringing a patient into the clinic or emergency room, many patients go a year or more without seeing their primary care providers.⁸ During that time, an immense amount of information is underreported or completely lost. Capturing this information in real-time and more holistically over a person’s lifetime of care could provide physicians better insight to both better manage and more fully evaluate the success of treatment plans by tracking patient symptoms, pain, and functional status over time. With this more longitudinal view of the patient, we see a pathway towards achieving the Quadruple Aim: patients who are more supported will achieve better outcomes at lower cost, they will have a better experience, and care teams will be empowered to focus their time on more satisfying activities rather than repetitive administrative tasks.

Corresponding author: James A. Colbert, MD, MBA; [email protected]

Disclosures: Dr. Flyckt and Dr. Colbert are employed by Memora Health, an organization that helps health care systems digitize and automate care journeys.

From Memora Health (Dr. Flyckt and Dr. Colbert), San Francisco, CA; and Harvard Medical School (Dr. Colbert), Boston, MA.

A close relative was recently diagnosed with follicular lymphoma. He was cared for at a high-ranked cancer center by physicians with demonstrated expertise, and even had the support of a care navigator. Still, he was often left feeling overwhelmed and confused, holding an inch-thick stack of papers, instructions, and pamphlets. As he left his treatment planning visit, reeling from the emotional burden of his diagnosis and all the unfamiliar terminology, he didn’t know what to do or what to expect. Later, when he experienced early signs of tumor lysis syndrome, he struggled to reach his care team for triage and guidance. When he went to the emergency room, his oncologist was never informed.

This scenario is unfortunately common, and versions of this scenario play out thousands of times each day across the US health system. Within the clinic and hospital setting, patients receive excellent care from their providers, but a disconnect emerges once the patient leaves these medical settings: patients at home struggle to find guidance and support, while care teams lack the tools to engage patients between visits or monitor their health across care settings, providers, or episodes of care.

Leveraging Technology to Move From Episodes of Care to Complex Care Journeys

The use of automated messaging, artificial intelligence and natural language processing–driven chat experiences, and text-based support is becoming more common. However, health care lags behind other industries in the adoption of these technologies.^1,2 The slow pace can be warranted, given that health care is more complicated and higher risk than inquiring about a lost package, ordering groceries, or applying for a mortgage. At the same time, many of the consumer engagement tools used to guide an applicant through the multiple steps and complexities of their home loan process or to prompt viewers to select new shows to binge have applications in health care.

Over the past few years, technologies have emerged that guide patients through complex care journeys and allow care teams to monitor and engage patients between visits. These solutions come in different formats, but generally patients can receive messages on their phones that contain disease-specific educational content, prompts to fill prescriptions and take medications, and reminders and guidance on how to prepare for appointments and procedures. These programs also collect relevant data from patients through survey and electronic patient-reported outcomes instruments, as well as connected patient monitoring devices, that help track patient progress and identify issues as they arise. Many programs also incorporate symptom triage pathways and use natural language processing to respond automatically to patient questions and concerns.^3,4

These technology solutions can automate many tasks that in the past required a care team member to spend hours on the phone. Newly freed from such repetitive tasks, care teams can now focus on more in-depth interactions with those patients who are most in need—the types of interactions that are more satisfying and rewarding. Such assistance is particularly needed today with the staffing shortages faced by most health systems.⁵

In addition, technology allows teams to see the panel of patients they are caring for and to quickly identify and take action on any specific needs or issues. Care teams can focus on any patient and see where they are in their journey. When appropriate, some solutions also allow care teams to engage directly with patients through text-messaging, creating a seamless experience and unified communication channel. Ideally, these solutions should be linked or embedded within the electronic health record or other primary system of record, so that teams can easily access these tools through their existing workflows and avoid creating yet another interface to navigate.

The Impact of Low-Tech Solutions to Deliver High-Touch Support

There is evidence showing that digital patient navigation tools impact patient care. In the oncology setting, patients with a digital navigator have achieved over 95% adherence rates with complex oral chemotherapy regimens (Memora Health Unpublished Data. 2022.). In the postpartum setting, a text message–based program improved screening rates for postpartum depression and did so with very high patient satisfaction ratings.⁶ Particularly notable is the fact that this depression screening program achieved these results in a population that was predominantly low income, with more than half belonging to underrepresented minority populations.⁶

We believe these digital patient navigation technologies, specifically low-tech solutions that don’t require app downloads, portal log-ins, or high-speed internet, will transform care delivery over the next 5 to 10 years. Successful management of complex conditions like diabetes or cancer requires more than 3 hours of care each day,⁷ yet most patients spend only 1 or 2 hours per month directly interacting with their health care providers. However, most patients carry their phones with them at all times, and artificial intelligence–enabled text support is “always on” to provide support, monitoring, and guidance, wherever a patient happens to be when assistance is needed.

Shifting the Model to Support a Lifetime of Care

While still in the early stages of development, these tools have the potential to radically alter the practice of medicine, shifting the focus from episodic interactions to continuous journey-based care delivery. Outside of an acute event bringing a patient into the clinic or emergency room, many patients go a year or more without seeing their primary care providers.⁸ During that time, an immense amount of information is underreported or completely lost. Capturing this information in real-time and more holistically over a person’s lifetime of care could provide physicians better insight to both better manage and more fully evaluate the success of treatment plans by tracking patient symptoms, pain, and functional status over time. With this more longitudinal view of the patient, we see a pathway towards achieving the Quadruple Aim: patients who are more supported will achieve better outcomes at lower cost, they will have a better experience, and care teams will be empowered to focus their time on more satisfying activities rather than repetitive administrative tasks.

Corresponding author: James A. Colbert, MD, MBA; [email protected]

Disclosures: Dr. Flyckt and Dr. Colbert are employed by Memora Health, an organization that helps health care systems digitize and automate care journeys.

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.