CAD & Atherosclerosis

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

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

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

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

Women with preexisting ischemic heart disease without another cardiac diagnosis have a higher risk of severe maternal morbidity and mortality than women with no cardiac disease, a new study suggests.

However, after adjustment for other comorbidities, the risk associated with isolated preexisting ischemic heart disease without additional evidence of cardiomyopathy was relatively similar to that of other low-risk cardiac diseases.

“These are reassuring findings,” lead author of the study, Anna E. Denoble, MD, Yale University, New Haven, Conn., told this news organization. “The risk is not zero. Women with preexisting ischemic heart disease are at a small increased risk compared to women without preexisting cardiac disease. But with good control of cardiovascular risk factors, these women have a good chance of a positive outcome.”

The study was published online in JACC: Advances.

“To our knowledge, this study provides the largest analysis to date examining the risk of severe morbidity and mortality among pregnant people with pre-existing ischemic heart disease,” the authors noted.

Dr. Denoble, a maternal and fetal medicine specialist, explained that in recent years, there has been an increase in the number of patients with preexisting ischemic heart disease who are considering pregnancy or who are pregnant when they present, but there is little information on outcomes for these patients.

The diagnosis of ischemic heart disease is not included in the main classification used for heart disease in pregnancy – the modified World Health Organization classification, Dr. Denoble noted. “This classification includes information on pregnancy outcomes in women with many cardiac conditions, including arrhythmias, congenital heart disease, heart failure, and aortic aneurysm, but ischemic heart disease is missing.”

She suggested this is probably because ischemic heart disease is regarded as a condition that occurs mainly in older people. “But we are seeing more and more women with ischemic heart disease who are pregnant or considering pregnancy. This could be because women are now often older when considering pregnancy, and also risk factors for ischemic heart disease, such as obesity and diabetes, are becoming more frequent in younger women.”

The researchers conducted the current study to investigate pregnancy outcomes for these women.

The retrospective cohort study analyzed data from the Nationwide Readmissions Database on women who had experienced a delivery hospitalization from Oct. 1, 2015, to Dec. 31, 2018. They compared outcomes for women with isolated preexisting ischemic heart disease with those of women who had no apparent cardiac condition and to those with mild or more severe cardiac conditions included in the mWHO classification after controlling for other comorbidities.

The primary outcome was severe maternal morbidity or death. Dr. Denoble explained that severe maternal morbidity includes mechanical ventilation, blood transfusion, and hysterectomy – the more severe maternal adverse outcomes of pregnancy.

Results showed that, of 11,556,136 delivery hospitalizations, 65,331 patients had another cardiac diagnosis, and 3,009 had ischemic heart disease alone. Patients with ischemic heart disease were older, and rates of diabetes and hypertension were higher.

In unadjusted analyses, adverse outcomes were more common among patients with ischemic heart disease alone than among patients with no cardiac disease and mild cardiac conditions (mWHO class I-II cardiac disease).

Of those with preexisting ischemic heart disease, 6.6% experienced severe maternal morbidity or death, compared with 1.5% of those without a cardiac disease (unadjusted relative risk vs. no cardiac disease, 4.3; 95% confidence interval, 3.5-5.2).

In comparison, 4.2% of women with mWHO I-II cardiac diseases and 23.1% of those with more severe mWHO II/III-IV cardiac diseases experienced severe maternal morbidity or death.

Similar differences were noted for nontransfusion severe maternal morbidity and mortality, as well as cardiac severe maternal morbidity and mortality.

After adjustment, ischemic heart disease alone was associated with a higher risk of severe maternal morbidity or death compared to no cardiac disease (adjusted RR, 1.51; 95% CI, 1.19-1.92).

In comparison, the aRR was 1.90 for WHO class I-II diseases and 5.87 (95% CI, 5.49-6.27) for more severe cardiac conditions defined as WHO II/III-IV diseases.

Risk for nontransfusion severe maternal morbidity or death (aRR, 1.60) and cardiac severe maternal morbidity or death (aRR, 2.98) were also higher for those with ischemic heart disease than for women without any cardiac disease.

There were no significant differences in preterm birth for those with preexisting ischemic heart disease compared to those with no cardiac disease after adjustment.

The risk of severe maternal morbidity and mortality, nontransfusion severe maternal morbidity and mortality, and cardiac severe maternal morbidity and mortality for ischemic heart disease alone most closely approximated that of mWHO class I or II cardiac diseases, the researchers said.

“We found that individuals with preexisting ischemic heart disease had a rate of severe maternal morbidity/mortality in the same range as those with other cardiac diagnoses in the mild cardiac disease classification (class I or II),” Dr. Denoble commented.

“This prognosis suggests it is very reasonable for these women to consider pregnancy. The risk of adverse outcomes is not so high that pregnancy is contraindicated,” she added.

Dr. Denoble said this information will be very helpful when counseling women with preexisting ischemic heart disease who are considering pregnancy. “These patients may need some extra monitoring, but in general, they have a high chance of a good outcome,” she noted.

“I would still advise these women to register with a high-risk obstetrics provider to have a baseline cardiovascular pregnancy evaluation. As long as that is reassuring, then further frequent intensive supervision may not be necessary,” she said.

However, the authors pointed out, “it is important to communicate to patients that while pregnancy may be considered low risk in the setting of pre-existing ischemic heart disease, 6.6% of patients with pre-existing ischemic heart disease alone did experience severe maternal morbidity or death during the delivery hospitalization.”

They added that other medical comorbidities should be factored into discussions regarding the risks of pregnancy.

The researchers also noted that the study was limited to evaluation of maternal outcomes occurring during the delivery hospitalization and that additional research that assesses rates of maternal adverse cardiac events and maternal morbidity occurring prior to or after the delivery hospitalization would be beneficial.

Future studies examining the potential gradation in risk associated with additional cardiac comorbidities in individuals with preexisting ischemic heart disease would also be worthwhile, they added.

The study was supported by funding from the National Institutes of Health and the Foundation for Women and Girls with Blood Disorders. The authors disclosed no relevant financial relationships.

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

A new strategy for the management of atherosclerotic plaque as a source of major adverse cardiac events is needed with the focus shifting from the flow-limiting coronary artery luminal lesions to the overall atherosclerotic burden, be it obstructive or nonobstructive, according to a review article.

The article, by Peter H. Stone, MD, and Peter Libby, MD, Brigham and Women’s Hospital, Boston, and William E. Boden, MD, Boston University School of Medicine, was published online in JAMA Cardiology.  

The review explored new data from vascular biology, atherosclerosis imaging, natural history outcome studies, and large-scale clinical trials that support what the authors refer to as “The Plaque Hypothesis” – the idea that major adverse cardiac events such as myocardial infarction and cardiac death are triggered by destabilization of vulnerable plaque, which may be obstructive or nonobstructive.

“We need to consider embracing a new management strategy that directs our diagnostic and management focus to evaluate the entire length of the atheromatous coronary artery and broaden the target of our therapeutic intervention to include all regions of the plaque (both flow-limiting and non–flow-limiting), even those that are distant from the presumed ischemia-producing obstruction,” the authors concluded.

Dr. Stone explained to this news organization that, for several decades, the medical community has focused on plaques causing severe obstruction of coronary arteries as being responsible for major adverse cardiac events. This approach – known as the Ischemia Hypothesis – has been the accepted strategy for many years, with all guidelines advising the identification of the stenoses that cause the most obstruction for treatment with stenting.

However, the authors pointed out that a number of studies have now suggested that, while these severe obstructive stenoses cause angina, they do not seem to be responsible for the hard events of MI, acute coronary syndrome (ACS), and cardiac death. 

Several studies including the COURAGE trial and BARI-2D, and the recent ISCHEMIA trial have all failed to show a reduction in these hard endpoints by intervening on these severe obstructive lesions, Dr. Stone noted. 

“We present evidence for a new approach – that it is the composition and vascular biology of the atherosclerotic plaques that cause MI, ACS, and cardiac death, rather than simply how obstructive they are,” he said.  

Dr. Stone pointed out that plaque seen on a coronary angiogram looks at only the lumen of the artery, but plaque is primarily based in the wall of the artery, and if that plaque is inflamed it can easily be the culprit responsible for adverse events even without encroaching into the lumen.

“Our paper describes many factors which can cause plaques to destabilize and cause an ACS. These include anatomical, biochemical, and biomechanical features that together cause plaque rupture or erosion and precipitate a clinical event. It is not sufficient to just look for obstructive plaques on a coronary angiogram,” he said. “We are barking up the wrong tree. We need to look for inflamed plaque in the whole wall of the coronary arteries.”

The authors described different factors that identify a plaque at high risk of destabilization. These include a large area of vulnerable plaque, a thin-cap atheroma, a severe inflamed core, macrocalcifications, a large plaque burden, and a physical profile that would encourage a thrombus to become trapped.  

“Atherosclerotic plaques are very heterogeneous and complex structures and it is not just the mountain peaks but also the lower foothills that can precipitate a flow-limiting obstruction,” Dr. Stone noted. 

“The slope of the mountain is probably very important in the ability for a thrombus to form. If the slope is gradual there isn’t a problem. But if the slope is jagged with sharp edges this can cause a thrombus to become trapped. We need to look at the entirety of plaque and all its risk features to identify the culprit areas that could cause MI or cardiac death. These are typically not the obstructive plaques we have all been fixated on for many years,” he added. 

“We need to focus on plaque heterogeneity. Once plaque is old and just made up of scar tissue which is not inflamed it does not cause much [of] a problem – we can probably just leave it alone. Some of these obstructive plaques may cause some angina but many do not cause major cardiac events unless they have other high-risk features,” he said. 

“Cardiac events are still caused by obstruction of blood flow but that can be an abrupt process where a thrombus attaches itself to an area of destabilized plaque. These areas of plaque were not necessarily obstructing to start with. We believe that this is the explanation behind the observation that 50% of all people who have an MI (half of which are fatal) do not have symptoms beforehand,” Dr. Stone commented. 

Because these areas of destabilized plaque do not cause symptoms, he believes that vast populations of people with established cardiovascular risk factors should undergo screening. “At the moment we wait for people to experience chest pain or to have an MI – that is far too little too late.” 

To identify these areas of high-risk plaques, imaging techniques looking inside the artery wall are needed such as intravascular ultrasound. However, this is an invasive procedure, and the noninvasive coronary CT angiography also gives a good picture, so it is probably the best way to begin as a wider screening modality, with more invasive screening methods then used in those found to be at risk, Dr. Stone suggested.  

Plaques that are identified as likely to destabilize can be treated with percutaneous coronary intervention and stenting.  

While systemic therapies are useful, those currently available are not sufficient, Dr. Stone noted. For example, there are still high levels of major cardiac events in patients treated with the PCSK9 inhibitors, which bring about very large reductions in LDL cholesterol. “These therapies are beneficial, but they are not enough on their own. So, these areas of unstable plaque would need to be treated with stenting or something similar. We believe that the intervention of stenting is good but at present it is targeted at the wrong areas,” he stated.  

“Clearly what we’ve been doing – stenting only obstructive lesions – does not reduce hard clinical events. Imaging methods have improved so much in recent years that we can now identify high-risk areas of plaque. This whole field of studying the vulnerable plaque has been ongoing for many years, but it is only recently that imaging methods have become good enough to identify plaques at risk. This field is now coming of age,” he added.

The next steps are to start identifying these plaques in larger populations, more accurately characterizing those at the highest risk, and then performing randomized trials of preemptive intervention in those believed to be at highest risk, and follow up for clinical events, Dr. Stone explained.  

Advances in detecting unstable plaque may also permit early evaluation of novel therapeutics and gauge the intensity of lifestyle and disease-modifying pharmacotherapy, the authors suggested.

This work was supported in part by the National Heart, Lung, and Blood Institute, the American Heart Association, the RRM Charitable Fund, the Simard Fund, and the Schaubert Family. Dr. Libby is an unpaid consultant to or involved in clinical trials with Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Moderna, Novartis, PlaqueTec, TenSixteen Bio, Soley Thereapeutics, and XBiotech.

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

A new strategy for the management of atherosclerotic plaque as a source of major adverse cardiac events is needed with the focus shifting from the flow-limiting coronary artery luminal lesions to the overall atherosclerotic burden, be it obstructive or nonobstructive, according to a review article.

The article, by Peter H. Stone, MD, and Peter Libby, MD, Brigham and Women’s Hospital, Boston, and William E. Boden, MD, Boston University School of Medicine, was published online in JAMA Cardiology.  

The review explored new data from vascular biology, atherosclerosis imaging, natural history outcome studies, and large-scale clinical trials that support what the authors refer to as “The Plaque Hypothesis” – the idea that major adverse cardiac events such as myocardial infarction and cardiac death are triggered by destabilization of vulnerable plaque, which may be obstructive or nonobstructive.

“We need to consider embracing a new management strategy that directs our diagnostic and management focus to evaluate the entire length of the atheromatous coronary artery and broaden the target of our therapeutic intervention to include all regions of the plaque (both flow-limiting and non–flow-limiting), even those that are distant from the presumed ischemia-producing obstruction,” the authors concluded.

Dr. Stone explained to this news organization that, for several decades, the medical community has focused on plaques causing severe obstruction of coronary arteries as being responsible for major adverse cardiac events. This approach – known as the Ischemia Hypothesis – has been the accepted strategy for many years, with all guidelines advising the identification of the stenoses that cause the most obstruction for treatment with stenting.

However, the authors pointed out that a number of studies have now suggested that, while these severe obstructive stenoses cause angina, they do not seem to be responsible for the hard events of MI, acute coronary syndrome (ACS), and cardiac death. 

Several studies including the COURAGE trial and BARI-2D, and the recent ISCHEMIA trial have all failed to show a reduction in these hard endpoints by intervening on these severe obstructive lesions, Dr. Stone noted. 

“We present evidence for a new approach – that it is the composition and vascular biology of the atherosclerotic plaques that cause MI, ACS, and cardiac death, rather than simply how obstructive they are,” he said.  

Dr. Stone pointed out that plaque seen on a coronary angiogram looks at only the lumen of the artery, but plaque is primarily based in the wall of the artery, and if that plaque is inflamed it can easily be the culprit responsible for adverse events even without encroaching into the lumen.

“Our paper describes many factors which can cause plaques to destabilize and cause an ACS. These include anatomical, biochemical, and biomechanical features that together cause plaque rupture or erosion and precipitate a clinical event. It is not sufficient to just look for obstructive plaques on a coronary angiogram,” he said. “We are barking up the wrong tree. We need to look for inflamed plaque in the whole wall of the coronary arteries.”

The authors described different factors that identify a plaque at high risk of destabilization. These include a large area of vulnerable plaque, a thin-cap atheroma, a severe inflamed core, macrocalcifications, a large plaque burden, and a physical profile that would encourage a thrombus to become trapped.  

“Atherosclerotic plaques are very heterogeneous and complex structures and it is not just the mountain peaks but also the lower foothills that can precipitate a flow-limiting obstruction,” Dr. Stone noted. 

“The slope of the mountain is probably very important in the ability for a thrombus to form. If the slope is gradual there isn’t a problem. But if the slope is jagged with sharp edges this can cause a thrombus to become trapped. We need to look at the entirety of plaque and all its risk features to identify the culprit areas that could cause MI or cardiac death. These are typically not the obstructive plaques we have all been fixated on for many years,” he added. 

“We need to focus on plaque heterogeneity. Once plaque is old and just made up of scar tissue which is not inflamed it does not cause much [of] a problem – we can probably just leave it alone. Some of these obstructive plaques may cause some angina but many do not cause major cardiac events unless they have other high-risk features,” he said. 

“Cardiac events are still caused by obstruction of blood flow but that can be an abrupt process where a thrombus attaches itself to an area of destabilized plaque. These areas of plaque were not necessarily obstructing to start with. We believe that this is the explanation behind the observation that 50% of all people who have an MI (half of which are fatal) do not have symptoms beforehand,” Dr. Stone commented. 

Because these areas of destabilized plaque do not cause symptoms, he believes that vast populations of people with established cardiovascular risk factors should undergo screening. “At the moment we wait for people to experience chest pain or to have an MI – that is far too little too late.” 

To identify these areas of high-risk plaques, imaging techniques looking inside the artery wall are needed such as intravascular ultrasound. However, this is an invasive procedure, and the noninvasive coronary CT angiography also gives a good picture, so it is probably the best way to begin as a wider screening modality, with more invasive screening methods then used in those found to be at risk, Dr. Stone suggested.  

Plaques that are identified as likely to destabilize can be treated with percutaneous coronary intervention and stenting.  

While systemic therapies are useful, those currently available are not sufficient, Dr. Stone noted. For example, there are still high levels of major cardiac events in patients treated with the PCSK9 inhibitors, which bring about very large reductions in LDL cholesterol. “These therapies are beneficial, but they are not enough on their own. So, these areas of unstable plaque would need to be treated with stenting or something similar. We believe that the intervention of stenting is good but at present it is targeted at the wrong areas,” he stated.  

“Clearly what we’ve been doing – stenting only obstructive lesions – does not reduce hard clinical events. Imaging methods have improved so much in recent years that we can now identify high-risk areas of plaque. This whole field of studying the vulnerable plaque has been ongoing for many years, but it is only recently that imaging methods have become good enough to identify plaques at risk. This field is now coming of age,” he added.

The next steps are to start identifying these plaques in larger populations, more accurately characterizing those at the highest risk, and then performing randomized trials of preemptive intervention in those believed to be at highest risk, and follow up for clinical events, Dr. Stone explained.  

Advances in detecting unstable plaque may also permit early evaluation of novel therapeutics and gauge the intensity of lifestyle and disease-modifying pharmacotherapy, the authors suggested.

This work was supported in part by the National Heart, Lung, and Blood Institute, the American Heart Association, the RRM Charitable Fund, the Simard Fund, and the Schaubert Family. Dr. Libby is an unpaid consultant to or involved in clinical trials with Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Moderna, Novartis, PlaqueTec, TenSixteen Bio, Soley Thereapeutics, and XBiotech.

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

A new strategy for the management of atherosclerotic plaque as a source of major adverse cardiac events is needed with the focus shifting from the flow-limiting coronary artery luminal lesions to the overall atherosclerotic burden, be it obstructive or nonobstructive, according to a review article.

The article, by Peter H. Stone, MD, and Peter Libby, MD, Brigham and Women’s Hospital, Boston, and William E. Boden, MD, Boston University School of Medicine, was published online in JAMA Cardiology.  

The review explored new data from vascular biology, atherosclerosis imaging, natural history outcome studies, and large-scale clinical trials that support what the authors refer to as “The Plaque Hypothesis” – the idea that major adverse cardiac events such as myocardial infarction and cardiac death are triggered by destabilization of vulnerable plaque, which may be obstructive or nonobstructive.

“We need to consider embracing a new management strategy that directs our diagnostic and management focus to evaluate the entire length of the atheromatous coronary artery and broaden the target of our therapeutic intervention to include all regions of the plaque (both flow-limiting and non–flow-limiting), even those that are distant from the presumed ischemia-producing obstruction,” the authors concluded.

Dr. Stone explained to this news organization that, for several decades, the medical community has focused on plaques causing severe obstruction of coronary arteries as being responsible for major adverse cardiac events. This approach – known as the Ischemia Hypothesis – has been the accepted strategy for many years, with all guidelines advising the identification of the stenoses that cause the most obstruction for treatment with stenting.

However, the authors pointed out that a number of studies have now suggested that, while these severe obstructive stenoses cause angina, they do not seem to be responsible for the hard events of MI, acute coronary syndrome (ACS), and cardiac death. 

Several studies including the COURAGE trial and BARI-2D, and the recent ISCHEMIA trial have all failed to show a reduction in these hard endpoints by intervening on these severe obstructive lesions, Dr. Stone noted. 

“We present evidence for a new approach – that it is the composition and vascular biology of the atherosclerotic plaques that cause MI, ACS, and cardiac death, rather than simply how obstructive they are,” he said.  

Dr. Stone pointed out that plaque seen on a coronary angiogram looks at only the lumen of the artery, but plaque is primarily based in the wall of the artery, and if that plaque is inflamed it can easily be the culprit responsible for adverse events even without encroaching into the lumen.

“Our paper describes many factors which can cause plaques to destabilize and cause an ACS. These include anatomical, biochemical, and biomechanical features that together cause plaque rupture or erosion and precipitate a clinical event. It is not sufficient to just look for obstructive plaques on a coronary angiogram,” he said. “We are barking up the wrong tree. We need to look for inflamed plaque in the whole wall of the coronary arteries.”

The authors described different factors that identify a plaque at high risk of destabilization. These include a large area of vulnerable plaque, a thin-cap atheroma, a severe inflamed core, macrocalcifications, a large plaque burden, and a physical profile that would encourage a thrombus to become trapped.  

“Atherosclerotic plaques are very heterogeneous and complex structures and it is not just the mountain peaks but also the lower foothills that can precipitate a flow-limiting obstruction,” Dr. Stone noted. 

“The slope of the mountain is probably very important in the ability for a thrombus to form. If the slope is gradual there isn’t a problem. But if the slope is jagged with sharp edges this can cause a thrombus to become trapped. We need to look at the entirety of plaque and all its risk features to identify the culprit areas that could cause MI or cardiac death. These are typically not the obstructive plaques we have all been fixated on for many years,” he added. 

“We need to focus on plaque heterogeneity. Once plaque is old and just made up of scar tissue which is not inflamed it does not cause much [of] a problem – we can probably just leave it alone. Some of these obstructive plaques may cause some angina but many do not cause major cardiac events unless they have other high-risk features,” he said. 

“Cardiac events are still caused by obstruction of blood flow but that can be an abrupt process where a thrombus attaches itself to an area of destabilized plaque. These areas of plaque were not necessarily obstructing to start with. We believe that this is the explanation behind the observation that 50% of all people who have an MI (half of which are fatal) do not have symptoms beforehand,” Dr. Stone commented. 

Because these areas of destabilized plaque do not cause symptoms, he believes that vast populations of people with established cardiovascular risk factors should undergo screening. “At the moment we wait for people to experience chest pain or to have an MI – that is far too little too late.” 

To identify these areas of high-risk plaques, imaging techniques looking inside the artery wall are needed such as intravascular ultrasound. However, this is an invasive procedure, and the noninvasive coronary CT angiography also gives a good picture, so it is probably the best way to begin as a wider screening modality, with more invasive screening methods then used in those found to be at risk, Dr. Stone suggested.  

Plaques that are identified as likely to destabilize can be treated with percutaneous coronary intervention and stenting.  

While systemic therapies are useful, those currently available are not sufficient, Dr. Stone noted. For example, there are still high levels of major cardiac events in patients treated with the PCSK9 inhibitors, which bring about very large reductions in LDL cholesterol. “These therapies are beneficial, but they are not enough on their own. So, these areas of unstable plaque would need to be treated with stenting or something similar. We believe that the intervention of stenting is good but at present it is targeted at the wrong areas,” he stated.  

“Clearly what we’ve been doing – stenting only obstructive lesions – does not reduce hard clinical events. Imaging methods have improved so much in recent years that we can now identify high-risk areas of plaque. This whole field of studying the vulnerable plaque has been ongoing for many years, but it is only recently that imaging methods have become good enough to identify plaques at risk. This field is now coming of age,” he added.

The next steps are to start identifying these plaques in larger populations, more accurately characterizing those at the highest risk, and then performing randomized trials of preemptive intervention in those believed to be at highest risk, and follow up for clinical events, Dr. Stone explained.  

Advances in detecting unstable plaque may also permit early evaluation of novel therapeutics and gauge the intensity of lifestyle and disease-modifying pharmacotherapy, the authors suggested.

This work was supported in part by the National Heart, Lung, and Blood Institute, the American Heart Association, the RRM Charitable Fund, the Simard Fund, and the Schaubert Family. Dr. Libby is an unpaid consultant to or involved in clinical trials with Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, MedImmune, Merck, Norvo Nordisk, Novartis, Pfizer, and Sanofi-Regeneron; and is a member of the scientific advisory board for Amgen, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, MedImmune, Moderna, Novartis, PlaqueTec, TenSixteen Bio, Soley Thereapeutics, and XBiotech.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

Age-related changes in general and cardiovascular health likely require modifications in how acute coronary syndrome (ACS) is diagnosed and managed in adults aged 75 and older, the American Heart Association says in a new scientific statement.

The statement outlines a framework to integrate geriatric risks into the management of ACS, including the diagnostic approach, pharmacotherapy, revascularization strategies, prevention of adverse events, and transition care planning.

The 31-page statement was published online in the AHA journal Circulation (2022 Dec 12. doi: 10.1161/CIR.0000000000001112). It updates a 2007 AHA statement on treatment of ACS in the elderly.
 

Complex patient group

Adults aged 75 and older make up roughly 30%-40% of all hospitalized patients with ACS and the majority of ACS-related deaths occur in this group, the writing group notes.

“Older patients have more pronounced anatomical changes and more severe functional impairment, and they are more likely to have additional health conditions,” writing group chair Abdulla A. Damluji, MD, PhD, director of the Inova Center of Outcomes Research in Fairfax, Va., notes in a news release.

“These include frailty, other chronic disorders (treated with multiple medications), physical dysfunction, cognitive decline and/or urinary incontinence – and these are not regularly studied in the context of ACS,” Dr. Damluji explained.

The writing group notes that the presence of one or more geriatric syndromes may substantially affect ACS clinical presentation, clinical course and prognosis, therapeutic decision-making, and response to treatment.

“It is therefore fundamental that clinicians caring for older patients with ACS be alert to the presence of geriatric syndromes and be able to integrate them into the care plan when appropriate,” they say.

They recommend a holistic, individualized, and patient-centered approach to ACS care in the elderly, taking into consideration coexisting and overlapping health issues.
 

Considerations for clinical care

The AHA statement offers several “considerations for clinical practice” with regard to ACS diagnosis and management in elderly adults. They include:

• ACS presentations without chest pain, such as shortness of breath, syncope, or sudden confusion, are more common in older adults.
• Many older adults have persistent elevations in cardiac troponin levels from myocardial fibrosis and kidney disease that diminish the positive predictive value of high-sensitivity cardiac troponin (hs-cTn) assays for identifying acute and chronic myocardial injury. For this reason, evaluating patterns of rise and fall is essential.
• Age-related changes in metabolism, weight, and muscle mass may require different choices in anticoagulant medications to lower bleeding risk.
• Clopidogrel (Plavix) is the preferred P2Y12 inhibitor because of a significantly lower bleeding profile than ticagrelor (Brilinta) or prasugrel (Effient). For patients with ST-segment myocardial infarction (STEMI) or complex anatomy, the use of ticagrelor is “reasonable.”
• Poor kidney function can increase the risk for contrast-induced acute kidney injury.
• Although the risks are greater, percutaneous coronary intervention or bypass surgery are beneficial in select older adults with ACS.
• Post-MI care should include cardiac rehabilitation tailored to address each patient’s circumstances and personal goals of care.
• For patients with cognitive difficulties and limited mobility, consider simplified medication plans with fewer doses per day and 90-day supplies to prevent the need for frequent refills.
• Patient care plans should be individualized, with input from a multidisciplinary team that may include cardiologists, surgeons, geriatricians, primary care clinicians, nutritionists, social workers, and family members.
• Determine a priori goals of care in older patients to help avoid an unwanted or futile intervention.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardiovascular Diseases in Older Populations Committee of the Council on Clinical Cardiology; the Council on Cardiovascular and Stroke Nursing; the Council on Cardiovascular Radiology and Intervention; and the Council on Lifestyle and Cardiometabolic Health.

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

A 70-year-old man with a history of coronary artery disease (CAD) is seen for concerns about erectile dysfunction (ED). He is requesting sildenafil. He has stable angina, having chest pain with exercise. He uses sublingual nitroglycerin (SL NTG prn) about three times a month. His blood pressure is 140/70 mm Hg. His pulse is 60 beats per minute. His current medications are lisinopril, atorvastatin, aspirin, and SL NTG tablets as needed.

What would you recommend?

A. No sildenafil; refer to urologist for other ED options.

B. Okay to use sildenafil if greater than 6 hours from NTG use.

C. Recommend tadalafil.

Is coprescribing nitrates and phosphodiesterase inhibitors safe?

The FDA warns against the use of phosphodiesterase inhibitors in patients taking nitrates. Combining nitrates with phosphodiesterase type 5 (PDE5) inhibitors is contraindicated because of a synergistic blood pressure lowering effect.¹ This warning/contraindication was based on theoretical concerns, as well as concern that of the first 130 deaths reported in patients who took sildenafil, 16 of the patients also were taking nitrates.²

Parker and colleagues studied the safety of giving IV nitroglycerin to patients with coronary artery disease (CAD) who have taken sildenafil.³ The study was a randomized, placebo-controlled, crossover trial. Participants received sildenafil 100 mg or placebo, then received intravenous NTG. Patients who received sildenafil had a 4-6 mm Hg systolic BP drop compared with those who took the placebo. There was no difference in severe events between the sildenafil and placebo groups. The blood levels of nitroglycerin in this study were very likely much higher than the levels that occur with SL NTG.

A recent study by Holt et al. looked at overall cardiovascular outcomes with coprescribing nitrates and phosphodiesterase inhibitors.⁴ The study was a case crossover design, using a nationwide Danish health registry over the period of 2000-2018. In 2000, the rate of coprescribing of phosphodiesterase inhibitors in ischemic heart disease patients on nitrates was .9 per 100 persons/year and rose to 19.5 prescriptions per 100 persons/year in 2018. During this same time, no statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for MI, cardiac arrest, syncope, stroke, or an adverse drug event.
 

Does nitroglycerin response help determine cause of chest pain?

Nitroglycerin response has long been used as a clinical indicator on whether a patient’s chest pain is cardiac or not. Eric A. Shry, MD, and his colleagues looked at the usefulness of nitroglycerin response in the treatment of chest pain as a predictor of ischemic chest pain in an emergency department setting.⁵

The study was a retrospective review of 223 patients who presented to the emergency department over a 5-month period with ongoing chest pain. They looked at patients who had ongoing chest pain in the emergency department, received nitroglycerin, and did not receive any therapy other than aspirin within 10 minutes of receiving nitroglycerin. Response to the drug was compared with the final diagnosis of cardiac versus noncardiac chest pain.

Of the patients with a final determination of cardiac chest pain, 88% had a nitroglycerin response, whereas 92% of the patients with noncardiac chest pain had a nitroglycerin response (P = .50).

Deborah B. Diercks, MD, and her colleagues looked at improvement in chest pain scores in the emergency department in patients treated with nitroglycerin and whether it correlated with a cardiac etiology of chest pain.⁶ The study was a prospective, observational study of 664 patients in an urban tertiary care emergency department over a 16-month period. An 11-point numeric chest pain scale was assessed and recorded by research assistants before and 5 minutes after receiving nitroglycerin. The scale ranged from 0 (no pain) to 10 (worst pain imaginable).

A final diagnosis of a cardiac etiology for chest pain was found in 18% of the patients in the study. Of the patients who had cardiac-related chest pain, 20% had no reduction in pain with nitroglycerin, compared with 19% of the patients without cardiac-related chest pain.

A complete or significant reduction in chest pain occurred with nitroglycerin in 31% of patients with cardiac chest pain and 27% of the patients without cardiac chest pain (P = .76).

Nitroglycerin response does not appear to be helpful in distinguishing cardiac from noncardiac chest pain, but a study by His and colleagues offers an interesting twist.⁷

The authors of this research studied 118 patients looking to see if the side effect of headache with nitroglycerin was more common in patients who did not have CAD than in those who did. All the patients had a varying degree of relief of chest pain with NTG administration within 10 minutes. In patients with normal coronary arteries or minimal CAD, 73% had headache caused by NTG, whereas in patients with obstructive CAD, only 23% had headache after NTG use.
 

Take-home messages

• Short acting nitroglycerin may not be a contraindication for phosphodiesterase inhibitor use.
• More data are still needed.
• Nitroglycerin response does not help distinguish chest pain from CAD from noncardiac causes.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Schwartz BG, Kloner RA. Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation. 2010;122:88-95.

2. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999 Sep 9;84(5B):11N-17N.

3. Parker JD et al. Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: A double-blind, placebo-controlled, randomized, crossover trial. Crit Care Med. 2007;35:1863-8.

4. Holt A et al. Adverse events associated with coprescription of phosphodiesterase type inhibitors and oral organic nitrates in male patients with ischemic heart disease. Ann Intern Med. 2022 Jun;175(6):774-82.

5. Shry EA et al. Usefulness of the response to sublingual nitroglycerin as a predictor of ischemic chest pain in the emergency department. Am J Cardiol. 2002 Dec 1;90(11):1264-6.

6. Diercks DB et al. Changes in the numeric descriptive scale for pain after sublingual nitroglycerin do not predict cardiac etiology of chest pain. Ann Emerg Med. 2005 Jun;45(6):581-5.

7. His DH et al. Headache response to glyceryl trinitrate in patients with and without obstructive coronary artery disease. Heart 2005;91:1164-6.

A 70-year-old man with a history of coronary artery disease (CAD) is seen for concerns about erectile dysfunction (ED). He is requesting sildenafil. He has stable angina, having chest pain with exercise. He uses sublingual nitroglycerin (SL NTG prn) about three times a month. His blood pressure is 140/70 mm Hg. His pulse is 60 beats per minute. His current medications are lisinopril, atorvastatin, aspirin, and SL NTG tablets as needed.

What would you recommend?

A. No sildenafil; refer to urologist for other ED options.

B. Okay to use sildenafil if greater than 6 hours from NTG use.

C. Recommend tadalafil.

Is coprescribing nitrates and phosphodiesterase inhibitors safe?

The FDA warns against the use of phosphodiesterase inhibitors in patients taking nitrates. Combining nitrates with phosphodiesterase type 5 (PDE5) inhibitors is contraindicated because of a synergistic blood pressure lowering effect.¹ This warning/contraindication was based on theoretical concerns, as well as concern that of the first 130 deaths reported in patients who took sildenafil, 16 of the patients also were taking nitrates.²

Parker and colleagues studied the safety of giving IV nitroglycerin to patients with coronary artery disease (CAD) who have taken sildenafil.³ The study was a randomized, placebo-controlled, crossover trial. Participants received sildenafil 100 mg or placebo, then received intravenous NTG. Patients who received sildenafil had a 4-6 mm Hg systolic BP drop compared with those who took the placebo. There was no difference in severe events between the sildenafil and placebo groups. The blood levels of nitroglycerin in this study were very likely much higher than the levels that occur with SL NTG.

A recent study by Holt et al. looked at overall cardiovascular outcomes with coprescribing nitrates and phosphodiesterase inhibitors.⁴ The study was a case crossover design, using a nationwide Danish health registry over the period of 2000-2018. In 2000, the rate of coprescribing of phosphodiesterase inhibitors in ischemic heart disease patients on nitrates was .9 per 100 persons/year and rose to 19.5 prescriptions per 100 persons/year in 2018. During this same time, no statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for MI, cardiac arrest, syncope, stroke, or an adverse drug event.
 

Does nitroglycerin response help determine cause of chest pain?

Nitroglycerin response has long been used as a clinical indicator on whether a patient’s chest pain is cardiac or not. Eric A. Shry, MD, and his colleagues looked at the usefulness of nitroglycerin response in the treatment of chest pain as a predictor of ischemic chest pain in an emergency department setting.⁵

The study was a retrospective review of 223 patients who presented to the emergency department over a 5-month period with ongoing chest pain. They looked at patients who had ongoing chest pain in the emergency department, received nitroglycerin, and did not receive any therapy other than aspirin within 10 minutes of receiving nitroglycerin. Response to the drug was compared with the final diagnosis of cardiac versus noncardiac chest pain.

Of the patients with a final determination of cardiac chest pain, 88% had a nitroglycerin response, whereas 92% of the patients with noncardiac chest pain had a nitroglycerin response (P = .50).

Deborah B. Diercks, MD, and her colleagues looked at improvement in chest pain scores in the emergency department in patients treated with nitroglycerin and whether it correlated with a cardiac etiology of chest pain.⁶ The study was a prospective, observational study of 664 patients in an urban tertiary care emergency department over a 16-month period. An 11-point numeric chest pain scale was assessed and recorded by research assistants before and 5 minutes after receiving nitroglycerin. The scale ranged from 0 (no pain) to 10 (worst pain imaginable).

A final diagnosis of a cardiac etiology for chest pain was found in 18% of the patients in the study. Of the patients who had cardiac-related chest pain, 20% had no reduction in pain with nitroglycerin, compared with 19% of the patients without cardiac-related chest pain.

A complete or significant reduction in chest pain occurred with nitroglycerin in 31% of patients with cardiac chest pain and 27% of the patients without cardiac chest pain (P = .76).

Nitroglycerin response does not appear to be helpful in distinguishing cardiac from noncardiac chest pain, but a study by His and colleagues offers an interesting twist.⁷

The authors of this research studied 118 patients looking to see if the side effect of headache with nitroglycerin was more common in patients who did not have CAD than in those who did. All the patients had a varying degree of relief of chest pain with NTG administration within 10 minutes. In patients with normal coronary arteries or minimal CAD, 73% had headache caused by NTG, whereas in patients with obstructive CAD, only 23% had headache after NTG use.
 

Take-home messages

• Short acting nitroglycerin may not be a contraindication for phosphodiesterase inhibitor use.
• More data are still needed.
• Nitroglycerin response does not help distinguish chest pain from CAD from noncardiac causes.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Schwartz BG, Kloner RA. Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation. 2010;122:88-95.

2. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999 Sep 9;84(5B):11N-17N.

3. Parker JD et al. Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: A double-blind, placebo-controlled, randomized, crossover trial. Crit Care Med. 2007;35:1863-8.

4. Holt A et al. Adverse events associated with coprescription of phosphodiesterase type inhibitors and oral organic nitrates in male patients with ischemic heart disease. Ann Intern Med. 2022 Jun;175(6):774-82.

5. Shry EA et al. Usefulness of the response to sublingual nitroglycerin as a predictor of ischemic chest pain in the emergency department. Am J Cardiol. 2002 Dec 1;90(11):1264-6.

6. Diercks DB et al. Changes in the numeric descriptive scale for pain after sublingual nitroglycerin do not predict cardiac etiology of chest pain. Ann Emerg Med. 2005 Jun;45(6):581-5.

7. His DH et al. Headache response to glyceryl trinitrate in patients with and without obstructive coronary artery disease. Heart 2005;91:1164-6.

A 70-year-old man with a history of coronary artery disease (CAD) is seen for concerns about erectile dysfunction (ED). He is requesting sildenafil. He has stable angina, having chest pain with exercise. He uses sublingual nitroglycerin (SL NTG prn) about three times a month. His blood pressure is 140/70 mm Hg. His pulse is 60 beats per minute. His current medications are lisinopril, atorvastatin, aspirin, and SL NTG tablets as needed.

What would you recommend?

A. No sildenafil; refer to urologist for other ED options.

B. Okay to use sildenafil if greater than 6 hours from NTG use.

C. Recommend tadalafil.

Is coprescribing nitrates and phosphodiesterase inhibitors safe?

The FDA warns against the use of phosphodiesterase inhibitors in patients taking nitrates. Combining nitrates with phosphodiesterase type 5 (PDE5) inhibitors is contraindicated because of a synergistic blood pressure lowering effect.¹ This warning/contraindication was based on theoretical concerns, as well as concern that of the first 130 deaths reported in patients who took sildenafil, 16 of the patients also were taking nitrates.²

Parker and colleagues studied the safety of giving IV nitroglycerin to patients with coronary artery disease (CAD) who have taken sildenafil.³ The study was a randomized, placebo-controlled, crossover trial. Participants received sildenafil 100 mg or placebo, then received intravenous NTG. Patients who received sildenafil had a 4-6 mm Hg systolic BP drop compared with those who took the placebo. There was no difference in severe events between the sildenafil and placebo groups. The blood levels of nitroglycerin in this study were very likely much higher than the levels that occur with SL NTG.

A recent study by Holt et al. looked at overall cardiovascular outcomes with coprescribing nitrates and phosphodiesterase inhibitors.⁴ The study was a case crossover design, using a nationwide Danish health registry over the period of 2000-2018. In 2000, the rate of coprescribing of phosphodiesterase inhibitors in ischemic heart disease patients on nitrates was .9 per 100 persons/year and rose to 19.5 prescriptions per 100 persons/year in 2018. During this same time, no statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for MI, cardiac arrest, syncope, stroke, or an adverse drug event.
 

Does nitroglycerin response help determine cause of chest pain?

Nitroglycerin response has long been used as a clinical indicator on whether a patient’s chest pain is cardiac or not. Eric A. Shry, MD, and his colleagues looked at the usefulness of nitroglycerin response in the treatment of chest pain as a predictor of ischemic chest pain in an emergency department setting.⁵

The study was a retrospective review of 223 patients who presented to the emergency department over a 5-month period with ongoing chest pain. They looked at patients who had ongoing chest pain in the emergency department, received nitroglycerin, and did not receive any therapy other than aspirin within 10 minutes of receiving nitroglycerin. Response to the drug was compared with the final diagnosis of cardiac versus noncardiac chest pain.

Of the patients with a final determination of cardiac chest pain, 88% had a nitroglycerin response, whereas 92% of the patients with noncardiac chest pain had a nitroglycerin response (P = .50).

Deborah B. Diercks, MD, and her colleagues looked at improvement in chest pain scores in the emergency department in patients treated with nitroglycerin and whether it correlated with a cardiac etiology of chest pain.⁶ The study was a prospective, observational study of 664 patients in an urban tertiary care emergency department over a 16-month period. An 11-point numeric chest pain scale was assessed and recorded by research assistants before and 5 minutes after receiving nitroglycerin. The scale ranged from 0 (no pain) to 10 (worst pain imaginable).

A final diagnosis of a cardiac etiology for chest pain was found in 18% of the patients in the study. Of the patients who had cardiac-related chest pain, 20% had no reduction in pain with nitroglycerin, compared with 19% of the patients without cardiac-related chest pain.

A complete or significant reduction in chest pain occurred with nitroglycerin in 31% of patients with cardiac chest pain and 27% of the patients without cardiac chest pain (P = .76).

Nitroglycerin response does not appear to be helpful in distinguishing cardiac from noncardiac chest pain, but a study by His and colleagues offers an interesting twist.⁷

The authors of this research studied 118 patients looking to see if the side effect of headache with nitroglycerin was more common in patients who did not have CAD than in those who did. All the patients had a varying degree of relief of chest pain with NTG administration within 10 minutes. In patients with normal coronary arteries or minimal CAD, 73% had headache caused by NTG, whereas in patients with obstructive CAD, only 23% had headache after NTG use.
 

Take-home messages

• Short acting nitroglycerin may not be a contraindication for phosphodiesterase inhibitor use.
• More data are still needed.
• Nitroglycerin response does not help distinguish chest pain from CAD from noncardiac causes.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Schwartz BG, Kloner RA. Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation. 2010;122:88-95.

2. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999 Sep 9;84(5B):11N-17N.

3. Parker JD et al. Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: A double-blind, placebo-controlled, randomized, crossover trial. Crit Care Med. 2007;35:1863-8.

4. Holt A et al. Adverse events associated with coprescription of phosphodiesterase type inhibitors and oral organic nitrates in male patients with ischemic heart disease. Ann Intern Med. 2022 Jun;175(6):774-82.

5. Shry EA et al. Usefulness of the response to sublingual nitroglycerin as a predictor of ischemic chest pain in the emergency department. Am J Cardiol. 2002 Dec 1;90(11):1264-6.

6. Diercks DB et al. Changes in the numeric descriptive scale for pain after sublingual nitroglycerin do not predict cardiac etiology of chest pain. Ann Emerg Med. 2005 Jun;45(6):581-5.

7. His DH et al. Headache response to glyceryl trinitrate in patients with and without obstructive coronary artery disease. Heart 2005;91:1164-6.

The randomized, placebo-controlled CLEAR Outcomes trial has shown a significant reduction in risk for a composite cardiovascular (CV) endpoint among its patients treated with the lipid-lowering agent bempedoic acid (Nexletol), the drug’s owner, Esperion, announced today.

The trial marks the first time an ATP-citrate lyase inhibitor has shown significant and “clinically meaningful” benefit for patients not adequately managed with standard lipid-modifying agents, Esperion president and CEO Sheldon Koenig said in a press release.

The brief statement provided only top-line results, without P values or other evidence of the magnitude of benefit in the active-therapy group. The company expects to present more complete results “at a key medical conference in the first quarter of 2023.”

CLEAR Outcomes had entered 14,014 patients with a history of or at high risk for CV disease events, elevated low-density lipoprotein cholesterol (LDL-C) levels, and demonstrated intolerance to at least two statins.

They were randomly assigned to bempedoic acid 180 mg once daily or placebo and followed for the primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial, conducted in 32 countries, launched in December 2016.  

Bempedoic acid is currently approved for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease on maximally tolerated statins who require additional LDL-C lowering, the company states.

Concomitant use of bempedoic acid with simvastatin or pravastatin, the press release says, may lead to increased statin concentrations and risk for “simvastatin- or pravastatin-related myopathy.” Therefore, “use with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.”

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

The randomized, placebo-controlled CLEAR Outcomes trial has shown a significant reduction in risk for a composite cardiovascular (CV) endpoint among its patients treated with the lipid-lowering agent bempedoic acid (Nexletol), the drug’s owner, Esperion, announced today.

The trial marks the first time an ATP-citrate lyase inhibitor has shown significant and “clinically meaningful” benefit for patients not adequately managed with standard lipid-modifying agents, Esperion president and CEO Sheldon Koenig said in a press release.

The brief statement provided only top-line results, without P values or other evidence of the magnitude of benefit in the active-therapy group. The company expects to present more complete results “at a key medical conference in the first quarter of 2023.”

CLEAR Outcomes had entered 14,014 patients with a history of or at high risk for CV disease events, elevated low-density lipoprotein cholesterol (LDL-C) levels, and demonstrated intolerance to at least two statins.

They were randomly assigned to bempedoic acid 180 mg once daily or placebo and followed for the primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial, conducted in 32 countries, launched in December 2016.  

Bempedoic acid is currently approved for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease on maximally tolerated statins who require additional LDL-C lowering, the company states.

Concomitant use of bempedoic acid with simvastatin or pravastatin, the press release says, may lead to increased statin concentrations and risk for “simvastatin- or pravastatin-related myopathy.” Therefore, “use with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.”

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

The randomized, placebo-controlled CLEAR Outcomes trial has shown a significant reduction in risk for a composite cardiovascular (CV) endpoint among its patients treated with the lipid-lowering agent bempedoic acid (Nexletol), the drug’s owner, Esperion, announced today.

The trial marks the first time an ATP-citrate lyase inhibitor has shown significant and “clinically meaningful” benefit for patients not adequately managed with standard lipid-modifying agents, Esperion president and CEO Sheldon Koenig said in a press release.

The brief statement provided only top-line results, without P values or other evidence of the magnitude of benefit in the active-therapy group. The company expects to present more complete results “at a key medical conference in the first quarter of 2023.”

CLEAR Outcomes had entered 14,014 patients with a history of or at high risk for CV disease events, elevated low-density lipoprotein cholesterol (LDL-C) levels, and demonstrated intolerance to at least two statins.

They were randomly assigned to bempedoic acid 180 mg once daily or placebo and followed for the primary endpoint of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial, conducted in 32 countries, launched in December 2016.  

Bempedoic acid is currently approved for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease on maximally tolerated statins who require additional LDL-C lowering, the company states.

Concomitant use of bempedoic acid with simvastatin or pravastatin, the press release says, may lead to increased statin concentrations and risk for “simvastatin- or pravastatin-related myopathy.” Therefore, “use with greater than 20 mg of simvastatin or 40 mg of pravastatin should be avoided.”

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

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

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

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

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

A new study has provided further reassurance on questions about the risk of intracerebral hemorrhage (ICH) with statins.

The Danish case-control study, which compared statin use in 2,164 case patients with ICH and in 86,255 matched control persons, found that current statin use was associated with a lower risk of having a first ICH and that the risk was further reduced with longer duration of statin use.

The study also showed that statin use was linked to a lower risk of ICH in the more superficial lobar areas of the brain and in the deeper, nonlobar locations. There was no difference in the magnitude of risk reduction between the two locations.

“Although this study is observational, I feel these data are strong, and the results are reassuring. It certainly does not suggest any increased risk of ICH with statins,” senior author David Gaist, PhD, Odense University Hospital, Denmark, said in an interview.

“On the contrary, it indicates a lower risk, which seems to be independent of the location of the bleed.”

The study was published online in Neurology.

The authors note that statins effectively reduce the occurrence of cardiovascular events and ischemic stroke in high-risk populations, but early randomized trials raised concerns of an increased risk of ICH among statin users who have a history of stroke.

Subsequent observational studies, including four meta-analyses, included patients with and those without prior stroke. The results were inconsistent, although most found no increase in bleeding. More recent studies have found a lower risk of ICH among statin users; the risk was inversely associated with the duration and intensity of statin treatment.

However, the researchers point out that few studies have assessed the association between statin use and the location of ICH. Hemorrhages that occur in the lobar region of the brain and those that occur in the nonlobar areas can have different pathophysiologies. Arteriolosclerosis, which is strongly associated with hypertension, is a common histologic finding in patients with ICH, regardless of hemorrhage location, while cerebral amyloid angiopathy (CAA) is associated with lobar but not nonlobar ICH.

The current study was conducted to look more closely at the relationship between statin use and hematoma location as a reflection of differences in the underlying pathophysiologies of lobar versus nonlobar ICH.

The researchers used Danish registries to identify all first-ever cases of spontaneous ICH that occurred between 2009 and 2018 in persons older than 55 years in the Southern Denmark region. Patients with traumatic ICH or ICH related to vascular malformations and tumors were excluded.

These cases were verified through medical records. ICH diagnoses were classified as having a lobar or nonlobar location, and patients were matched for age, sex, and calendar year to general population control persons. The nationwide prescription registry was also analyzed to ascertain use of statins and other medications.

The study included 989 patients with lobar ICH who were matched to 39,500 control persons and 1,175 patients with nonlobar ICH who were matched to 46,755 control persons.

Results showed that current statin use was associated with a 16%-17% relative reduction in ICH risk. There was no difference with respect to ICH location.

For lobar ICH, statin use showed an adjusted odds ratio of 0.83 (95% confidence interval, 0.70-0.98); for nonlobar ICH, the adjusted odds ratio was 0.84 (95% CI, 0.72-0.98).

Longer duration of statin use was associated with a greater reduction in risk of ICH; use for more than 5 years was associated with a relative reduction of ICH of 33%-38%, again with no difference with regard to ICH location.

For lobar ICH, statin use for more than 5 years showed an adjusted odds ratio of 0.67 (95% CI, 0.51-0.87); and for nonlobar ICH, the adjusted odds ratio was 0.62 (95% CI, 0.48-0.80).

“We suspected that statins may have more of an effect in reducing nonlobar ICH, as this type is considered to be more associated with arteriosclerosis, compared with lobar ICH,” Dr. Gaist explained. “But we didn’t find that. We found that taking statins was associated with a similar reduction in risk of both lobar and nonlobar ICH.”

Although amyloid angiopathy can contribute to lobar ICH, arteriosclerosis is still involved in the majority of cases, he noted. He cited a recent population-based U.K. study that showed that while histologically verified CAA was present in 58% of patients with a lobar ICH, most also had evidence of arteriosclerosis, with only 13% having isolated CAA pathology.

“If statins exert their effect on reducing ICH by reducing arteriosclerosis, which is likely, then this observation of arteriosclerosis pathology being prevalent in both lobar and nonlobar ICH locations would explain our results,” Dr. Gaist commented.

“Strengths of our study include the large numbers involved and the fact that the patients are unselected. We tried to find everyone who had had a first ICH in a well-defined region of Denmark, so issues of selection are less of a concern than in some other studies,” he noted.

He also pointed out that all the ICH diagnoses were verified from medical records and that in a substudy, brain scans were evaluated, with investigators masked to clinical data to evaluate the location and characteristics of the hematoma. In addition, data on statin use were collected prospectively from a nationwide prescription registry.
 

Interaction with antihypertensives, anticoagulants?

Other results from the study suggest a possible interaction between statin use and antihypertensive and anticoagulant drugs.

Data showed that the lower ICH risk was restricted to patients who received statins and antihypertensive drugs concurrently. Conversely, only patients who were not concurrently taking anticoagulants had a lower risk of ICH in association with statin use.

Dr. Gaist suggested that the lack of a reduction in ICH with statins among patients taking anticoagulants could be because the increased risk of ICH with anticoagulants was stronger than the reduced risk with statins.

Regarding the fact that the reduced risk of ICH with statins was only observed among individuals who were also taking antihypertensive medication, Dr. Gaist noted that because hypertension is such an important risk factor for ICH, “it may be that to get the true benefit of statins, patients have to have their hypertension controlled.”

However, an alternative explanation could that the finding is a result of “healthy adherer” bias, in which people who take antihypertensive medication and follow a healthy lifestyle as advised would be more likely to take statins.

“The observational nature of our study does not allow us to determine the extent to which associations are causal,” the authors say.

Dr. Gaist also noted that an important caveat in this study is that they focused on individuals who had had a first ICH.

“This data does not inform us about those who have already had an ICH and are taking statins. But we are planning to look at this in our next study,” he said.

The study was funded by the Novo Nordisk Foundation. Dr. Gaist has received speaker honorarium from Bristol-Myers Squibb and Pfizer unrelated to this work.

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

These should be the best of times for geriatric medicine.

The baby boom has become a senior surge, bringing in a rapidly growing pool of aging patients for geriatricians to treat. According to the U.S. Census Bureau, more than 56 million adults aged 65 and older live in the United States. They account for about 17% of the nation’s population. That number is expected to hit 73 million by 2030 and 86 million by 2050.

The American Geriatrics Society estimates that 30% of older people require the attention of geriatricians. These clinicians excel in managing complex cases – patients with multiple comorbidities, such as coronary artery disease, dementia, and osteoporosis, who are taking a half dozen, and often more, medications.

But instead of thriving, geriatrics as a medical specialty appears to be hobbling. In the 2010s, geriatricians called for “25,000 [such specialists] by 2025.” As of 2021, 7123 certified geriatricians were practicing in the United States, according to the American Board of Medical Specialties.

The Health Resources and Services Administration, a federal agency that addresses medical workforce shortages, estimates that there will be 6,230 geriatricians by 2025, or approximately 1 for every 3,000 older adults requiring geriatric care. HRSA projects a shortage of 27,000 geriatricians by 2025.

The specialty has faced an uphill battle to attract fellows. This year, only 43% of the nation’s 177 geriatrics fellowship slots were filled, according to November’s National Resident Match Program report. Family medicine–based geriatrics achieved only a 32% fill rate, while internal medicine–based programs saw a rate of 45%.

“Our numbers are shrinking so we need another approach to make sure older adults get the care they need and deserve,” said G. Michael Harper, MD, president of the 6,000-member AGS.

But Dr. Harper, who practices at the University of California, San Francisco, and the San Francisco VA Medical Center, added a positive note: “We may be struggling to increase the number of board-certified geriatricians, but the field itself has made a lot of progress in terms of improving clinical care through advancements in science and in the ways we deliver care.”

Dr. Harper cited the Hospital Elder Life Program, a hospital model developed at the Harvard-affiliated Marcus Institute for Aging Research, which uses an interprofessional team and trained volunteers to prevent delirium and functional decline. HELP has been adopted by more than 200 hospitals worldwide and has been successful at returning older adults to their homes or previous living situations with maintained or improved ability to function, he said.

Mark Supiano, MD, professor and chief of geriatrics at the University of Utah, Salt Lake City, said the specialty has been in shortage mode since ABMS recognized it in 1988. He was in the initial cohort of fellowship-trained geriatricians, sitting for the first certifying exam in geriatrics offered that year.

“Back then, the demographic imperative of the aging of our society was on the horizon. We’re living it now. I knew enough to recognize it was coming and saw an opportunity,” Dr. Supiano said in an interview. “There was so much then that we didn’t know about how to understand aging or how to care for older adults that there really was such a knowledge gap.”

Dr. Supiano is an associate editor of Hazzard’s Geriatric Medicine and Gerontology (McGraw-Hill Education), which has more than doubled in pages and word count during his career.
 

Unfavorable finances

Katherine Thompson, MD, director of the geriatrics fellowship program at the University of Chicago and codirector of UChicago’s Successful Aging and Frailty Evaluation Clinic, said money is a major reason for the struggle. “I think probably the biggest driver is financial,” she said. “A lot of people are graduating medical school with really astronomical amounts of medical school loans.”

Geriatricians, like other doctors, carry a large debt – $200,000, on average, not counting undergraduate debt, according to the Association of American Medical Colleges.

But the typical geriatrician earns less than an internist or family medicine doctor who doesn’t undergo the additional year of training, Dr. Thompson said. “There’s not a lot of financial motivation to do this fellowship,” she said.

The jobs website Zippia reports that geriatricians earned roughly $165,000 per year on average in 2022. The average annual incomes in 2022 were $191,000 for pediatricians, $215,000 for family physicians, and $223,000 for internists, according to the site.

In other words, Dr. Harper said, “geriatrics is one of the few professions where you can actually do additional training and make less money.”

The reason for the pay issue is simple: Geriatricians treat patients covered by Medicare, whose reimbursement schedules lag behind those of commercial insurers. The Kaiser Family Foundation reported in 2020 that private insurance paid 143% of Medicare rates on average for physician services.

Dr. Harper said overall compensation for geriatricians has “not gained a lot of traction,” but they can earn comfortable livings.

Still, representation of the specialty on the American Medical Association’s Relative Value Scale Update Committee has led to approval by the Centers for Medicare & Medicaid Services of billing codes that pay geriatricians “for what they do. Examples include chronic care management, advance care planning, and dementia evaluation,” he said.

But the geriatrician gap goes beyond money.

Ageism, too, may play a role in residents not choosing geriatrics.

“Our culture is ageist. It definitely focuses on youth and looks at aging as being loss rather than just a change in what works well and what doesn’t work well,” said Mary Tinetti, MD, a geriatrician and researcher at Yale University, New Haven, Conn. “Ageism happens among physicians, just because they’re part of the broader society.”
 

Time for a new goal?

Dr. Tinetti said she’s optimistic that new ideas about geriatricians teaching other primary care clinicians about the tenets of geriatric medicine, which offer a wholistic approach to comorbidities, such as diabetes, atrial fibrillation, dementia, hypertension, hyperlipidemia, and polypharmacy problems faced by this population, especially those 85 and older.

She has called on her profession to abandon the goal of increasing the numbers of board-certified geriatricians – whom she refers to as big “G” geriatricians. She instead wants to develop a “small, elite workforce” that discovers and tests geriatrics principles through research, teaches these principles to all healthcare professions and to the public, and disseminates and implements the policies.

“We need a cadre of geriatricians who train all other clinicians in the care of older adults,” Dr. Tinetti said. “The goal is not more geriatricians but rather the preparation of all clinicians in the care of older adults.”

Dr. Thompson said geriatricians are teaching primary care specialists, nurses, social workers, and other health care providers the principles of age-friendly care. AGS has for the past 20 years led a program called the Geriatrics for Specialists Initiative to increase geriatrics knowledge and expertise of surgical and medical specialists.

Some specialties have taken the cue and have added geriatrics-related hyphens through additional training: geriatric-emergency, geriatric-general surgery, geriatric-hospitalists, and more.

HRSA runs programs to encourage physicians to train as geriatricians and geriatrics faculty, and it encourages the geriatrics interdisciplinary team approach.

Richard Olague, director of public affairs for HRSA, said his agency has invested over $160 million over the past 4 years in the education and training of geriatricians and other health care professionals who care for the elderly through its Geriatrics Workforce Enhancement Program and Geriatrics Academic Career Awards Program. In the academic year 2020-2021, the two programs trained 109 geriatricians; 456 other geriatric/gerontology providers and students; 44,450 other healthcare workforce professionals and students; and served 17,666 patients and 5,409 caregivers.

Dr. Harper, like his fellow geriatricians, tells young doctors that geriatrics is a fulfilling specialty.

“I get to care for the whole person and sometimes their families, too, and in the process form rich and meaningful relationships. And while I’m rarely in the position to cure, I always have the ability to care,” he said. “Sometimes that can mean being an advocate trying to make sure my patients receive the care they need, and other times it might mean protecting them from burdensome care that is unlikely to lead to any meaningful benefit. There is great reward in all of that.”

Dr. Supiano said geriatric patients are being helped by the Age-Friendly Health System initiative of the John A. Hartford Foundation and the Institute for Healthcare Improvement in partnership with the American Hospital Association and the Catholic Health Association of the United States. This is sort of a seal of approval for facilities committed to age-friendly care.

“When you go to your hospital, if they don’t have this age-friendly health system banner on the front door ... you either ask why that is not there, or you vote with your feet and go to another health system that is age friendly,” he said. “Geriatricians are eternal optimists.”

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

These should be the best of times for geriatric medicine.

The baby boom has become a senior surge, bringing in a rapidly growing pool of aging patients for geriatricians to treat. According to the U.S. Census Bureau, more than 56 million adults aged 65 and older live in the United States. They account for about 17% of the nation’s population. That number is expected to hit 73 million by 2030 and 86 million by 2050.

The American Geriatrics Society estimates that 30% of older people require the attention of geriatricians. These clinicians excel in managing complex cases – patients with multiple comorbidities, such as coronary artery disease, dementia, and osteoporosis, who are taking a half dozen, and often more, medications.

But instead of thriving, geriatrics as a medical specialty appears to be hobbling. In the 2010s, geriatricians called for “25,000 [such specialists] by 2025.” As of 2021, 7123 certified geriatricians were practicing in the United States, according to the American Board of Medical Specialties.

The Health Resources and Services Administration, a federal agency that addresses medical workforce shortages, estimates that there will be 6,230 geriatricians by 2025, or approximately 1 for every 3,000 older adults requiring geriatric care. HRSA projects a shortage of 27,000 geriatricians by 2025.

The specialty has faced an uphill battle to attract fellows. This year, only 43% of the nation’s 177 geriatrics fellowship slots were filled, according to November’s National Resident Match Program report. Family medicine–based geriatrics achieved only a 32% fill rate, while internal medicine–based programs saw a rate of 45%.

“Our numbers are shrinking so we need another approach to make sure older adults get the care they need and deserve,” said G. Michael Harper, MD, president of the 6,000-member AGS.

But Dr. Harper, who practices at the University of California, San Francisco, and the San Francisco VA Medical Center, added a positive note: “We may be struggling to increase the number of board-certified geriatricians, but the field itself has made a lot of progress in terms of improving clinical care through advancements in science and in the ways we deliver care.”

Dr. Harper cited the Hospital Elder Life Program, a hospital model developed at the Harvard-affiliated Marcus Institute for Aging Research, which uses an interprofessional team and trained volunteers to prevent delirium and functional decline. HELP has been adopted by more than 200 hospitals worldwide and has been successful at returning older adults to their homes or previous living situations with maintained or improved ability to function, he said.

Mark Supiano, MD, professor and chief of geriatrics at the University of Utah, Salt Lake City, said the specialty has been in shortage mode since ABMS recognized it in 1988. He was in the initial cohort of fellowship-trained geriatricians, sitting for the first certifying exam in geriatrics offered that year.

“Back then, the demographic imperative of the aging of our society was on the horizon. We’re living it now. I knew enough to recognize it was coming and saw an opportunity,” Dr. Supiano said in an interview. “There was so much then that we didn’t know about how to understand aging or how to care for older adults that there really was such a knowledge gap.”

Dr. Supiano is an associate editor of Hazzard’s Geriatric Medicine and Gerontology (McGraw-Hill Education), which has more than doubled in pages and word count during his career.
 

Unfavorable finances

Katherine Thompson, MD, director of the geriatrics fellowship program at the University of Chicago and codirector of UChicago’s Successful Aging and Frailty Evaluation Clinic, said money is a major reason for the struggle. “I think probably the biggest driver is financial,” she said. “A lot of people are graduating medical school with really astronomical amounts of medical school loans.”

Geriatricians, like other doctors, carry a large debt – $200,000, on average, not counting undergraduate debt, according to the Association of American Medical Colleges.

But the typical geriatrician earns less than an internist or family medicine doctor who doesn’t undergo the additional year of training, Dr. Thompson said. “There’s not a lot of financial motivation to do this fellowship,” she said.

The jobs website Zippia reports that geriatricians earned roughly $165,000 per year on average in 2022. The average annual incomes in 2022 were $191,000 for pediatricians, $215,000 for family physicians, and $223,000 for internists, according to the site.

In other words, Dr. Harper said, “geriatrics is one of the few professions where you can actually do additional training and make less money.”

The reason for the pay issue is simple: Geriatricians treat patients covered by Medicare, whose reimbursement schedules lag behind those of commercial insurers. The Kaiser Family Foundation reported in 2020 that private insurance paid 143% of Medicare rates on average for physician services.

Dr. Harper said overall compensation for geriatricians has “not gained a lot of traction,” but they can earn comfortable livings.

Still, representation of the specialty on the American Medical Association’s Relative Value Scale Update Committee has led to approval by the Centers for Medicare & Medicaid Services of billing codes that pay geriatricians “for what they do. Examples include chronic care management, advance care planning, and dementia evaluation,” he said.

But the geriatrician gap goes beyond money.

Ageism, too, may play a role in residents not choosing geriatrics.

“Our culture is ageist. It definitely focuses on youth and looks at aging as being loss rather than just a change in what works well and what doesn’t work well,” said Mary Tinetti, MD, a geriatrician and researcher at Yale University, New Haven, Conn. “Ageism happens among physicians, just because they’re part of the broader society.”
 

Time for a new goal?

Dr. Tinetti said she’s optimistic that new ideas about geriatricians teaching other primary care clinicians about the tenets of geriatric medicine, which offer a wholistic approach to comorbidities, such as diabetes, atrial fibrillation, dementia, hypertension, hyperlipidemia, and polypharmacy problems faced by this population, especially those 85 and older.

She has called on her profession to abandon the goal of increasing the numbers of board-certified geriatricians – whom she refers to as big “G” geriatricians. She instead wants to develop a “small, elite workforce” that discovers and tests geriatrics principles through research, teaches these principles to all healthcare professions and to the public, and disseminates and implements the policies.

“We need a cadre of geriatricians who train all other clinicians in the care of older adults,” Dr. Tinetti said. “The goal is not more geriatricians but rather the preparation of all clinicians in the care of older adults.”

Dr. Thompson said geriatricians are teaching primary care specialists, nurses, social workers, and other health care providers the principles of age-friendly care. AGS has for the past 20 years led a program called the Geriatrics for Specialists Initiative to increase geriatrics knowledge and expertise of surgical and medical specialists.

Some specialties have taken the cue and have added geriatrics-related hyphens through additional training: geriatric-emergency, geriatric-general surgery, geriatric-hospitalists, and more.

HRSA runs programs to encourage physicians to train as geriatricians and geriatrics faculty, and it encourages the geriatrics interdisciplinary team approach.

Richard Olague, director of public affairs for HRSA, said his agency has invested over $160 million over the past 4 years in the education and training of geriatricians and other health care professionals who care for the elderly through its Geriatrics Workforce Enhancement Program and Geriatrics Academic Career Awards Program. In the academic year 2020-2021, the two programs trained 109 geriatricians; 456 other geriatric/gerontology providers and students; 44,450 other healthcare workforce professionals and students; and served 17,666 patients and 5,409 caregivers.

Dr. Harper, like his fellow geriatricians, tells young doctors that geriatrics is a fulfilling specialty.

“I get to care for the whole person and sometimes their families, too, and in the process form rich and meaningful relationships. And while I’m rarely in the position to cure, I always have the ability to care,” he said. “Sometimes that can mean being an advocate trying to make sure my patients receive the care they need, and other times it might mean protecting them from burdensome care that is unlikely to lead to any meaningful benefit. There is great reward in all of that.”

Dr. Supiano said geriatric patients are being helped by the Age-Friendly Health System initiative of the John A. Hartford Foundation and the Institute for Healthcare Improvement in partnership with the American Hospital Association and the Catholic Health Association of the United States. This is sort of a seal of approval for facilities committed to age-friendly care.

“When you go to your hospital, if they don’t have this age-friendly health system banner on the front door ... you either ask why that is not there, or you vote with your feet and go to another health system that is age friendly,” he said. “Geriatricians are eternal optimists.”

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

These should be the best of times for geriatric medicine.

The baby boom has become a senior surge, bringing in a rapidly growing pool of aging patients for geriatricians to treat. According to the U.S. Census Bureau, more than 56 million adults aged 65 and older live in the United States. They account for about 17% of the nation’s population. That number is expected to hit 73 million by 2030 and 86 million by 2050.

The American Geriatrics Society estimates that 30% of older people require the attention of geriatricians. These clinicians excel in managing complex cases – patients with multiple comorbidities, such as coronary artery disease, dementia, and osteoporosis, who are taking a half dozen, and often more, medications.

But instead of thriving, geriatrics as a medical specialty appears to be hobbling. In the 2010s, geriatricians called for “25,000 [such specialists] by 2025.” As of 2021, 7123 certified geriatricians were practicing in the United States, according to the American Board of Medical Specialties.

The Health Resources and Services Administration, a federal agency that addresses medical workforce shortages, estimates that there will be 6,230 geriatricians by 2025, or approximately 1 for every 3,000 older adults requiring geriatric care. HRSA projects a shortage of 27,000 geriatricians by 2025.

The specialty has faced an uphill battle to attract fellows. This year, only 43% of the nation’s 177 geriatrics fellowship slots were filled, according to November’s National Resident Match Program report. Family medicine–based geriatrics achieved only a 32% fill rate, while internal medicine–based programs saw a rate of 45%.

“Our numbers are shrinking so we need another approach to make sure older adults get the care they need and deserve,” said G. Michael Harper, MD, president of the 6,000-member AGS.

But Dr. Harper, who practices at the University of California, San Francisco, and the San Francisco VA Medical Center, added a positive note: “We may be struggling to increase the number of board-certified geriatricians, but the field itself has made a lot of progress in terms of improving clinical care through advancements in science and in the ways we deliver care.”

Dr. Harper cited the Hospital Elder Life Program, a hospital model developed at the Harvard-affiliated Marcus Institute for Aging Research, which uses an interprofessional team and trained volunteers to prevent delirium and functional decline. HELP has been adopted by more than 200 hospitals worldwide and has been successful at returning older adults to their homes or previous living situations with maintained or improved ability to function, he said.

Mark Supiano, MD, professor and chief of geriatrics at the University of Utah, Salt Lake City, said the specialty has been in shortage mode since ABMS recognized it in 1988. He was in the initial cohort of fellowship-trained geriatricians, sitting for the first certifying exam in geriatrics offered that year.

“Back then, the demographic imperative of the aging of our society was on the horizon. We’re living it now. I knew enough to recognize it was coming and saw an opportunity,” Dr. Supiano said in an interview. “There was so much then that we didn’t know about how to understand aging or how to care for older adults that there really was such a knowledge gap.”

Dr. Supiano is an associate editor of Hazzard’s Geriatric Medicine and Gerontology (McGraw-Hill Education), which has more than doubled in pages and word count during his career.
 

Unfavorable finances

Katherine Thompson, MD, director of the geriatrics fellowship program at the University of Chicago and codirector of UChicago’s Successful Aging and Frailty Evaluation Clinic, said money is a major reason for the struggle. “I think probably the biggest driver is financial,” she said. “A lot of people are graduating medical school with really astronomical amounts of medical school loans.”

Geriatricians, like other doctors, carry a large debt – $200,000, on average, not counting undergraduate debt, according to the Association of American Medical Colleges.

But the typical geriatrician earns less than an internist or family medicine doctor who doesn’t undergo the additional year of training, Dr. Thompson said. “There’s not a lot of financial motivation to do this fellowship,” she said.

The jobs website Zippia reports that geriatricians earned roughly $165,000 per year on average in 2022. The average annual incomes in 2022 were $191,000 for pediatricians, $215,000 for family physicians, and $223,000 for internists, according to the site.

In other words, Dr. Harper said, “geriatrics is one of the few professions where you can actually do additional training and make less money.”

The reason for the pay issue is simple: Geriatricians treat patients covered by Medicare, whose reimbursement schedules lag behind those of commercial insurers. The Kaiser Family Foundation reported in 2020 that private insurance paid 143% of Medicare rates on average for physician services.

Dr. Harper said overall compensation for geriatricians has “not gained a lot of traction,” but they can earn comfortable livings.

Still, representation of the specialty on the American Medical Association’s Relative Value Scale Update Committee has led to approval by the Centers for Medicare & Medicaid Services of billing codes that pay geriatricians “for what they do. Examples include chronic care management, advance care planning, and dementia evaluation,” he said.

But the geriatrician gap goes beyond money.

Ageism, too, may play a role in residents not choosing geriatrics.

“Our culture is ageist. It definitely focuses on youth and looks at aging as being loss rather than just a change in what works well and what doesn’t work well,” said Mary Tinetti, MD, a geriatrician and researcher at Yale University, New Haven, Conn. “Ageism happens among physicians, just because they’re part of the broader society.”
 

Time for a new goal?

Dr. Tinetti said she’s optimistic that new ideas about geriatricians teaching other primary care clinicians about the tenets of geriatric medicine, which offer a wholistic approach to comorbidities, such as diabetes, atrial fibrillation, dementia, hypertension, hyperlipidemia, and polypharmacy problems faced by this population, especially those 85 and older.

She has called on her profession to abandon the goal of increasing the numbers of board-certified geriatricians – whom she refers to as big “G” geriatricians. She instead wants to develop a “small, elite workforce” that discovers and tests geriatrics principles through research, teaches these principles to all healthcare professions and to the public, and disseminates and implements the policies.

“We need a cadre of geriatricians who train all other clinicians in the care of older adults,” Dr. Tinetti said. “The goal is not more geriatricians but rather the preparation of all clinicians in the care of older adults.”

Dr. Thompson said geriatricians are teaching primary care specialists, nurses, social workers, and other health care providers the principles of age-friendly care. AGS has for the past 20 years led a program called the Geriatrics for Specialists Initiative to increase geriatrics knowledge and expertise of surgical and medical specialists.

Some specialties have taken the cue and have added geriatrics-related hyphens through additional training: geriatric-emergency, geriatric-general surgery, geriatric-hospitalists, and more.

HRSA runs programs to encourage physicians to train as geriatricians and geriatrics faculty, and it encourages the geriatrics interdisciplinary team approach.

Richard Olague, director of public affairs for HRSA, said his agency has invested over $160 million over the past 4 years in the education and training of geriatricians and other health care professionals who care for the elderly through its Geriatrics Workforce Enhancement Program and Geriatrics Academic Career Awards Program. In the academic year 2020-2021, the two programs trained 109 geriatricians; 456 other geriatric/gerontology providers and students; 44,450 other healthcare workforce professionals and students; and served 17,666 patients and 5,409 caregivers.

Dr. Harper, like his fellow geriatricians, tells young doctors that geriatrics is a fulfilling specialty.

“I get to care for the whole person and sometimes their families, too, and in the process form rich and meaningful relationships. And while I’m rarely in the position to cure, I always have the ability to care,” he said. “Sometimes that can mean being an advocate trying to make sure my patients receive the care they need, and other times it might mean protecting them from burdensome care that is unlikely to lead to any meaningful benefit. There is great reward in all of that.”

Dr. Supiano said geriatric patients are being helped by the Age-Friendly Health System initiative of the John A. Hartford Foundation and the Institute for Healthcare Improvement in partnership with the American Hospital Association and the Catholic Health Association of the United States. This is sort of a seal of approval for facilities committed to age-friendly care.

“When you go to your hospital, if they don’t have this age-friendly health system banner on the front door ... you either ask why that is not there, or you vote with your feet and go to another health system that is age friendly,” he said. “Geriatricians are eternal optimists.”

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

Automated alerts to aid clinical decision-making are designed with the best of intentions but can be easy to ignore or overlook. But a randomized trial testing such electronic alerts or “nudges” for promoting statin prescribing may have identified a few design features that help their success, researchers say.

In the trial’s primary finding, for example, reminders displayed to primary care physicians in the electronic health record worked best when the system also reached out to the patient.

Ariel Skelley/DigitalVision/Getty Images

Reminders sent only to the clinician also boosted statin prescribing, but not as well, and nudging only the patient didn’t work at all, compared to a nudge-free usual care approach. The patient-only nudges consisted of text messages explaining why a statin prescription may figure in their upcoming appointment.
 

Nudge trustworthiness

Importantly, the clinician nudges were more than simply reminders to consider a statin prescription, Mitesh S. Patel, MD, MBA, Ascension Health, St. Louis, told this news organization. They also displayed the patient’s atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and explained why a statin may be appropriate. He thinks that information, often left out of such clinical decision support alerts, increases physician trust in them.

In another key feature, Dr. Patel said, the EHR nudges themselves were actionable – that is, they were functional in ways that streamlined the prescribing process. In particular, they include checkbox shortcuts to prescribing statins at appropriate patient-specific dosages, making the entire process “faster and easier,” said Dr. Patel, who is senior author on the study published in JAMA Cardiology with lead author Srinath Adusumalli, MD, University of Pennsylvania, Philadelphia.

The timing may matter as well, he observed. In previous iterations of the study’s EHR nudge system, the nudge would appear “when you open the chart,” he said. “Now, it’s when you go to the orders section, which is when you’re going to be in the mindset of ordering prescriptions and tests.”

Prescription rates were higher with the doctor-patient nudges than with the doctor-only approach, Dr. Patel speculates, largely because the decision process for initiating statins is shared. “The most effective intervention is going to recognize that and try to bring the two groups together.”
 

Two text messages

The trial, with 158 participating physicians in 28 primary care practices, randomly assigned 4,131 patients to three intervention groups and one control group. Nudges were sent only to the physician, only to the patient, or to both physician and patient; and there was a no-nudge usual-care group.

Patient nudges consisted of two text messages, one 4 days and another 15 minutes before the appointment, announcing that prescription of a statin “to reduce the chance of a heart attack” would be discussed with the physician, the report states.

Statins are grossly underprescribed nationally, it notes, and that was reflected in prescription rates seen during the study’s initial 12-month, no-intervention period of observation. Rates ranged from only 4.7% up to 6% of patients across the four assignment groups.

During the subsequent 6-month intervention period, however, the rates climbed in the doctor-only and doctor-plus-patient nudge groups compared with usual care, by 5.5 (P = .01) and 7.2 (P = .001) absolute percentage points, respectively.

The overall cohort’s mean age was 65.5. About half were male, 29% were Black, 66% were White, and 22.6% already had a cardiovascular disease diagnosis. The analysis was adjusted for calendar month and preintervention statin prescribing rates. Further adjustment for demographics, insurance type, household income, and comorbidities yielded results similar to the primary analysis, the report states.
 

The results in context

“Although the differences in the combined clinician and patient and clinician-only arms were small, this outcome needs to be interpreted in the context of the population in which the study was performed,” an editorial accompanying the published report states.

For example, “the majority of untreated patients were candidates for primary, not secondary, prevention, making this group of patients particularly challenging for seeing large effect sizes of interventions.”

Moreover, “There was a high baseline prescription rate of statins in the statin-eligible population (approximately 70%) and a high rate of already established patients,” write Faraz S. Ahmad, MD, and Stephen D. Persell, MD, of Northwestern University, Chicago.

Among the approximately 30% of patients who had not previously been prescribed statins, the true target of the nudge interventions, the published trial report states, about 98% were not seeing the physician for the first time.

So “this may not have been the first opportunity to discuss statins,” they write. “It is possible that many of these patients were resistant to statins in the past, which could have created a ceiling effect for prescribing rates.”

Dr. Patel reports owning and receiving personal fees from Catalyst Health and serving on an advisory board for and receiving personal fees from Humana. Dr. Adusumalli reports having been employed by CVS Health. Dr. Ahmad reports receiving consulting fees from Teladoc Livongo and Pfizer. Dr. Persell discloses receiving grants from Omron Healthcare.

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

Automated alerts to aid clinical decision-making are designed with the best of intentions but can be easy to ignore or overlook. But a randomized trial testing such electronic alerts or “nudges” for promoting statin prescribing may have identified a few design features that help their success, researchers say.

In the trial’s primary finding, for example, reminders displayed to primary care physicians in the electronic health record worked best when the system also reached out to the patient.

Ariel Skelley/DigitalVision/Getty Images

Reminders sent only to the clinician also boosted statin prescribing, but not as well, and nudging only the patient didn’t work at all, compared to a nudge-free usual care approach. The patient-only nudges consisted of text messages explaining why a statin prescription may figure in their upcoming appointment.
 

Nudge trustworthiness

Importantly, the clinician nudges were more than simply reminders to consider a statin prescription, Mitesh S. Patel, MD, MBA, Ascension Health, St. Louis, told this news organization. They also displayed the patient’s atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and explained why a statin may be appropriate. He thinks that information, often left out of such clinical decision support alerts, increases physician trust in them.

In another key feature, Dr. Patel said, the EHR nudges themselves were actionable – that is, they were functional in ways that streamlined the prescribing process. In particular, they include checkbox shortcuts to prescribing statins at appropriate patient-specific dosages, making the entire process “faster and easier,” said Dr. Patel, who is senior author on the study published in JAMA Cardiology with lead author Srinath Adusumalli, MD, University of Pennsylvania, Philadelphia.

The timing may matter as well, he observed. In previous iterations of the study’s EHR nudge system, the nudge would appear “when you open the chart,” he said. “Now, it’s when you go to the orders section, which is when you’re going to be in the mindset of ordering prescriptions and tests.”

Prescription rates were higher with the doctor-patient nudges than with the doctor-only approach, Dr. Patel speculates, largely because the decision process for initiating statins is shared. “The most effective intervention is going to recognize that and try to bring the two groups together.”
 

Two text messages

The trial, with 158 participating physicians in 28 primary care practices, randomly assigned 4,131 patients to three intervention groups and one control group. Nudges were sent only to the physician, only to the patient, or to both physician and patient; and there was a no-nudge usual-care group.

Patient nudges consisted of two text messages, one 4 days and another 15 minutes before the appointment, announcing that prescription of a statin “to reduce the chance of a heart attack” would be discussed with the physician, the report states.

Statins are grossly underprescribed nationally, it notes, and that was reflected in prescription rates seen during the study’s initial 12-month, no-intervention period of observation. Rates ranged from only 4.7% up to 6% of patients across the four assignment groups.

During the subsequent 6-month intervention period, however, the rates climbed in the doctor-only and doctor-plus-patient nudge groups compared with usual care, by 5.5 (P = .01) and 7.2 (P = .001) absolute percentage points, respectively.

The overall cohort’s mean age was 65.5. About half were male, 29% were Black, 66% were White, and 22.6% already had a cardiovascular disease diagnosis. The analysis was adjusted for calendar month and preintervention statin prescribing rates. Further adjustment for demographics, insurance type, household income, and comorbidities yielded results similar to the primary analysis, the report states.
 

The results in context

“Although the differences in the combined clinician and patient and clinician-only arms were small, this outcome needs to be interpreted in the context of the population in which the study was performed,” an editorial accompanying the published report states.

For example, “the majority of untreated patients were candidates for primary, not secondary, prevention, making this group of patients particularly challenging for seeing large effect sizes of interventions.”

Moreover, “There was a high baseline prescription rate of statins in the statin-eligible population (approximately 70%) and a high rate of already established patients,” write Faraz S. Ahmad, MD, and Stephen D. Persell, MD, of Northwestern University, Chicago.

Among the approximately 30% of patients who had not previously been prescribed statins, the true target of the nudge interventions, the published trial report states, about 98% were not seeing the physician for the first time.

So “this may not have been the first opportunity to discuss statins,” they write. “It is possible that many of these patients were resistant to statins in the past, which could have created a ceiling effect for prescribing rates.”

Dr. Patel reports owning and receiving personal fees from Catalyst Health and serving on an advisory board for and receiving personal fees from Humana. Dr. Adusumalli reports having been employed by CVS Health. Dr. Ahmad reports receiving consulting fees from Teladoc Livongo and Pfizer. Dr. Persell discloses receiving grants from Omron Healthcare.

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

Automated alerts to aid clinical decision-making are designed with the best of intentions but can be easy to ignore or overlook. But a randomized trial testing such electronic alerts or “nudges” for promoting statin prescribing may have identified a few design features that help their success, researchers say.

In the trial’s primary finding, for example, reminders displayed to primary care physicians in the electronic health record worked best when the system also reached out to the patient.

Ariel Skelley/DigitalVision/Getty Images

Reminders sent only to the clinician also boosted statin prescribing, but not as well, and nudging only the patient didn’t work at all, compared to a nudge-free usual care approach. The patient-only nudges consisted of text messages explaining why a statin prescription may figure in their upcoming appointment.
 

Nudge trustworthiness

Importantly, the clinician nudges were more than simply reminders to consider a statin prescription, Mitesh S. Patel, MD, MBA, Ascension Health, St. Louis, told this news organization. They also displayed the patient’s atherosclerotic cardiovascular disease (ASCVD) 10-year risk score and explained why a statin may be appropriate. He thinks that information, often left out of such clinical decision support alerts, increases physician trust in them.

In another key feature, Dr. Patel said, the EHR nudges themselves were actionable – that is, they were functional in ways that streamlined the prescribing process. In particular, they include checkbox shortcuts to prescribing statins at appropriate patient-specific dosages, making the entire process “faster and easier,” said Dr. Patel, who is senior author on the study published in JAMA Cardiology with lead author Srinath Adusumalli, MD, University of Pennsylvania, Philadelphia.

The timing may matter as well, he observed. In previous iterations of the study’s EHR nudge system, the nudge would appear “when you open the chart,” he said. “Now, it’s when you go to the orders section, which is when you’re going to be in the mindset of ordering prescriptions and tests.”

Prescription rates were higher with the doctor-patient nudges than with the doctor-only approach, Dr. Patel speculates, largely because the decision process for initiating statins is shared. “The most effective intervention is going to recognize that and try to bring the two groups together.”
 

Two text messages

The trial, with 158 participating physicians in 28 primary care practices, randomly assigned 4,131 patients to three intervention groups and one control group. Nudges were sent only to the physician, only to the patient, or to both physician and patient; and there was a no-nudge usual-care group.

Patient nudges consisted of two text messages, one 4 days and another 15 minutes before the appointment, announcing that prescription of a statin “to reduce the chance of a heart attack” would be discussed with the physician, the report states.

Statins are grossly underprescribed nationally, it notes, and that was reflected in prescription rates seen during the study’s initial 12-month, no-intervention period of observation. Rates ranged from only 4.7% up to 6% of patients across the four assignment groups.

During the subsequent 6-month intervention period, however, the rates climbed in the doctor-only and doctor-plus-patient nudge groups compared with usual care, by 5.5 (P = .01) and 7.2 (P = .001) absolute percentage points, respectively.

The overall cohort’s mean age was 65.5. About half were male, 29% were Black, 66% were White, and 22.6% already had a cardiovascular disease diagnosis. The analysis was adjusted for calendar month and preintervention statin prescribing rates. Further adjustment for demographics, insurance type, household income, and comorbidities yielded results similar to the primary analysis, the report states.
 

The results in context

“Although the differences in the combined clinician and patient and clinician-only arms were small, this outcome needs to be interpreted in the context of the population in which the study was performed,” an editorial accompanying the published report states.

For example, “the majority of untreated patients were candidates for primary, not secondary, prevention, making this group of patients particularly challenging for seeing large effect sizes of interventions.”

Moreover, “There was a high baseline prescription rate of statins in the statin-eligible population (approximately 70%) and a high rate of already established patients,” write Faraz S. Ahmad, MD, and Stephen D. Persell, MD, of Northwestern University, Chicago.

Among the approximately 30% of patients who had not previously been prescribed statins, the true target of the nudge interventions, the published trial report states, about 98% were not seeing the physician for the first time.

So “this may not have been the first opportunity to discuss statins,” they write. “It is possible that many of these patients were resistant to statins in the past, which could have created a ceiling effect for prescribing rates.”

Dr. Patel reports owning and receiving personal fees from Catalyst Health and serving on an advisory board for and receiving personal fees from Humana. Dr. Adusumalli reports having been employed by CVS Health. Dr. Ahmad reports receiving consulting fees from Teladoc Livongo and Pfizer. Dr. Persell discloses receiving grants from Omron Healthcare.

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

A novel approach for stratifying patients into one of two phenotypes for coronary artery disease (CAD) helped differentiate those who would benefit from percutaneous coronary intervention (PCI) from those who wouldn’t, researchers in Belgium reported in a subanalysis of a single-center, randomized clinical trial.

“What this study adds is that we are actually creating a refined definition of the appropriateness criteria for PCI,” lead study author Carlos Collet, MD, PhD, of the Cardiovascular Center at OLV Hospital in Aalst, Belgium, said in an interview. “We have been too long implanting stents in diffuse disease that actually have no benefit for the patient.”

The study found that patients with diffuse CAD were almost twice as likely to have residual angina 3 months after PCI than patients with focal CAD, with respective rates of 51.9% vs. 27.5% after PCI (P = .02).

The researchers analyzed 103 patients from the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) conducted at the Golden Jubilee National Hospital in Glasgow. Study patients completed the 7-item Seattle Angina Questionnaire at baseline and at 3 months after PCI, which provided the researchers information on outcomes.

The study, published in JACC: Cardiovascular Interventions, used median pullback pressure gradient (PPG) to define focal and diffuse CAD. The operators used the PressureWire X Guidewire (Abbott Vascular) to measure fractional flow reserve (FFR).

The procedure involved administering a 200-mcg bolus of intracoronary nitrate and then positioning the pressure wire sensor at the tip of the guide catheter equalized with aortic pressure. The pressure wire was then advanced to the position sensor in the distal third of the vessel. After hyperemia was induced, coronary flow reserve was assessed using bolus thermodilution. Manual FFR pullback maneuvers were done at a constant speed for 20-30 seconds. The PPG index was calculated post hoc from the manual FFR pullback recordings obtained pre-PCI.

In this study, patients with low PPG needed longer (48 mm vs. 37 mm; P = .015) and more (1.5 vs. 1.0; P = .036) stents during PCI, Dr. Collet and colleagues reported. They concluded that patients with low PPG can be treated with medical therapy.

“The beauty of the PPG is that everything happens before you implant the stent,” Dr. Collet said. “We’re starting to understand that we cannot treat diffuse disease with a focal disease therapy.”

The challenge with differentiating diffuse from focal CAD has been that it relies on visual assessment. “It’s subject to operator variability, and that’s the reason why there are no trials with focal or diffuse disease specifically because, until now, we didn’t have any metric that quantified the diffuseness or the focality of the disease,” Dr. Collet said.

The PPG itself isn’t novel, Dr. Collet said. “The novelty is that for first time we can quantify in a reproducible way the information from the pullback,” he added.

Courtesy Cardiovascular Research Foundation

“What this study tells us is that once you have a patient with diffuse coronary artery disease, don’t try PCI because it will not help half of them,” Patrick W. Serruys, MD, PhD, a cardiologist at the National University of Ireland, Galway, and author of the accompanying editorial, said in an interview.

He noted that one limitation of the study was that Dr. Collet and colleagues used mechanical PPG to measure the pressure gradient. “We use now a surrogate, which is angiography,” Dr. Serruys said. “It’s not exactly the same as a measurement of pressure with the pressure wire, but we know from many, many studies that it’s quite a good surrogate.” Future research should focus on use of angiography without the pressure wire to evaluate the pressure gradient.

The ongoing PPG Global registry will aim to further validate findings from the subanalysis, Dr. Collet said, and the PPG Primetime study will evaluate deferring PCI in patients with low PPG.

Dr. Collet disclosed relationships with Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, OpSens, Abbott Vascular and Philips Volcano. Dr. Serruys disclosed relationships with Sinomedical Sciences Technology, Sahajanand Medical Technological, Philips Volcano, Xeltis and HeartFlow.

A novel approach for stratifying patients into one of two phenotypes for coronary artery disease (CAD) helped differentiate those who would benefit from percutaneous coronary intervention (PCI) from those who wouldn’t, researchers in Belgium reported in a subanalysis of a single-center, randomized clinical trial.

“What this study adds is that we are actually creating a refined definition of the appropriateness criteria for PCI,” lead study author Carlos Collet, MD, PhD, of the Cardiovascular Center at OLV Hospital in Aalst, Belgium, said in an interview. “We have been too long implanting stents in diffuse disease that actually have no benefit for the patient.”

The study found that patients with diffuse CAD were almost twice as likely to have residual angina 3 months after PCI than patients with focal CAD, with respective rates of 51.9% vs. 27.5% after PCI (P = .02).

The researchers analyzed 103 patients from the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) conducted at the Golden Jubilee National Hospital in Glasgow. Study patients completed the 7-item Seattle Angina Questionnaire at baseline and at 3 months after PCI, which provided the researchers information on outcomes.

The study, published in JACC: Cardiovascular Interventions, used median pullback pressure gradient (PPG) to define focal and diffuse CAD. The operators used the PressureWire X Guidewire (Abbott Vascular) to measure fractional flow reserve (FFR).

The procedure involved administering a 200-mcg bolus of intracoronary nitrate and then positioning the pressure wire sensor at the tip of the guide catheter equalized with aortic pressure. The pressure wire was then advanced to the position sensor in the distal third of the vessel. After hyperemia was induced, coronary flow reserve was assessed using bolus thermodilution. Manual FFR pullback maneuvers were done at a constant speed for 20-30 seconds. The PPG index was calculated post hoc from the manual FFR pullback recordings obtained pre-PCI.

In this study, patients with low PPG needed longer (48 mm vs. 37 mm; P = .015) and more (1.5 vs. 1.0; P = .036) stents during PCI, Dr. Collet and colleagues reported. They concluded that patients with low PPG can be treated with medical therapy.

“The beauty of the PPG is that everything happens before you implant the stent,” Dr. Collet said. “We’re starting to understand that we cannot treat diffuse disease with a focal disease therapy.”

The challenge with differentiating diffuse from focal CAD has been that it relies on visual assessment. “It’s subject to operator variability, and that’s the reason why there are no trials with focal or diffuse disease specifically because, until now, we didn’t have any metric that quantified the diffuseness or the focality of the disease,” Dr. Collet said.

The PPG itself isn’t novel, Dr. Collet said. “The novelty is that for first time we can quantify in a reproducible way the information from the pullback,” he added.

Courtesy Cardiovascular Research Foundation

“What this study tells us is that once you have a patient with diffuse coronary artery disease, don’t try PCI because it will not help half of them,” Patrick W. Serruys, MD, PhD, a cardiologist at the National University of Ireland, Galway, and author of the accompanying editorial, said in an interview.

He noted that one limitation of the study was that Dr. Collet and colleagues used mechanical PPG to measure the pressure gradient. “We use now a surrogate, which is angiography,” Dr. Serruys said. “It’s not exactly the same as a measurement of pressure with the pressure wire, but we know from many, many studies that it’s quite a good surrogate.” Future research should focus on use of angiography without the pressure wire to evaluate the pressure gradient.

The ongoing PPG Global registry will aim to further validate findings from the subanalysis, Dr. Collet said, and the PPG Primetime study will evaluate deferring PCI in patients with low PPG.

Dr. Collet disclosed relationships with Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, OpSens, Abbott Vascular and Philips Volcano. Dr. Serruys disclosed relationships with Sinomedical Sciences Technology, Sahajanand Medical Technological, Philips Volcano, Xeltis and HeartFlow.

A novel approach for stratifying patients into one of two phenotypes for coronary artery disease (CAD) helped differentiate those who would benefit from percutaneous coronary intervention (PCI) from those who wouldn’t, researchers in Belgium reported in a subanalysis of a single-center, randomized clinical trial.

“What this study adds is that we are actually creating a refined definition of the appropriateness criteria for PCI,” lead study author Carlos Collet, MD, PhD, of the Cardiovascular Center at OLV Hospital in Aalst, Belgium, said in an interview. “We have been too long implanting stents in diffuse disease that actually have no benefit for the patient.”

The study found that patients with diffuse CAD were almost twice as likely to have residual angina 3 months after PCI than patients with focal CAD, with respective rates of 51.9% vs. 27.5% after PCI (P = .02).

The researchers analyzed 103 patients from the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) conducted at the Golden Jubilee National Hospital in Glasgow. Study patients completed the 7-item Seattle Angina Questionnaire at baseline and at 3 months after PCI, which provided the researchers information on outcomes.

The study, published in JACC: Cardiovascular Interventions, used median pullback pressure gradient (PPG) to define focal and diffuse CAD. The operators used the PressureWire X Guidewire (Abbott Vascular) to measure fractional flow reserve (FFR).

The procedure involved administering a 200-mcg bolus of intracoronary nitrate and then positioning the pressure wire sensor at the tip of the guide catheter equalized with aortic pressure. The pressure wire was then advanced to the position sensor in the distal third of the vessel. After hyperemia was induced, coronary flow reserve was assessed using bolus thermodilution. Manual FFR pullback maneuvers were done at a constant speed for 20-30 seconds. The PPG index was calculated post hoc from the manual FFR pullback recordings obtained pre-PCI.

In this study, patients with low PPG needed longer (48 mm vs. 37 mm; P = .015) and more (1.5 vs. 1.0; P = .036) stents during PCI, Dr. Collet and colleagues reported. They concluded that patients with low PPG can be treated with medical therapy.

“The beauty of the PPG is that everything happens before you implant the stent,” Dr. Collet said. “We’re starting to understand that we cannot treat diffuse disease with a focal disease therapy.”

The challenge with differentiating diffuse from focal CAD has been that it relies on visual assessment. “It’s subject to operator variability, and that’s the reason why there are no trials with focal or diffuse disease specifically because, until now, we didn’t have any metric that quantified the diffuseness or the focality of the disease,” Dr. Collet said.

The PPG itself isn’t novel, Dr. Collet said. “The novelty is that for first time we can quantify in a reproducible way the information from the pullback,” he added.

Courtesy Cardiovascular Research Foundation

“What this study tells us is that once you have a patient with diffuse coronary artery disease, don’t try PCI because it will not help half of them,” Patrick W. Serruys, MD, PhD, a cardiologist at the National University of Ireland, Galway, and author of the accompanying editorial, said in an interview.

He noted that one limitation of the study was that Dr. Collet and colleagues used mechanical PPG to measure the pressure gradient. “We use now a surrogate, which is angiography,” Dr. Serruys said. “It’s not exactly the same as a measurement of pressure with the pressure wire, but we know from many, many studies that it’s quite a good surrogate.” Future research should focus on use of angiography without the pressure wire to evaluate the pressure gradient.

The ongoing PPG Global registry will aim to further validate findings from the subanalysis, Dr. Collet said, and the PPG Primetime study will evaluate deferring PCI in patients with low PPG.

Dr. Collet disclosed relationships with Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, OpSens, Abbott Vascular and Philips Volcano. Dr. Serruys disclosed relationships with Sinomedical Sciences Technology, Sahajanand Medical Technological, Philips Volcano, Xeltis and HeartFlow.

A new meta-analysis of 884 studies evaluating 27 different types of antioxidant supplements has suggested that some of these micronutrients – including omega-3 fatty acids, folic acid, and coenzyme Q10 – may produce significant cardiovascular benefits.

Other antioxidant supplements that showed some evidence of reducing cardiovascular risk were omega-6 fatty acids, L-arginine, L-citrulline, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

No effect was seen with vitamin C, vitamin D, vitamin E, or selenium, and beta-carotene supplementation was linked to an increase in all-cause mortality in the analysis.

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

“Our systematic assessment and quantification of multiple differential effects of a wide variety of micronutrients and phytochemicals on cardiometabolic health indicate that an optimal nutritional strategy to promote cardiometabolic health will likely involve personalized combinations of these nutrients,” the authors, led by Peng An, PhD, China Agricultural University, Beijing, conclude.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” senior author Simin Liu, MD, professor of epidemiology and medicine at Brown University, Providence, R.I., said in an American College of Cardiology press release.

“The micronutrients identified require further validation in large, high-quality interventional trials to establish clinical efficacy to determine their long-term balance of risks and benefits,” the authors add.
 

Experts cautious

Experts in the field of cardiovascular risk and preventative medicine have urged caution in interpreting these results.

JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, told this news organization that she has concerns that some of the results in the meta-analysis may be inflated by publication bias and some are chance findings that haven’t been well replicated.

“Although this meta-analysis of micronutrients and cardiometabolic health was based on randomized clinical trials, the quality of randomized trials on this subject varies widely,” she noted.

“The study is informative, but the conclusions are only as good as the quality of the evidence. Some of the trials are limited by short duration, and included trials have a wide range of quality, dosing, inclusion criteria, imperfect blinding, and few of them focus on hard clinical events,” Dr. Manson said. “Also, with trials of this nature, the potential for publication bias warrants consideration, because many of the smaller trials with unfavorable or neutral results may remain unpublished or not even be submitted for publication.”   

However, she added, “despite these limitations, this is an important contribution to the literature on micronutrients and health – and goes a long way in separating the wheat from the chaff.”

Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at the Cleveland Clinic, was more critical of the meta-analysis.

“This study does not make sense. Some of the ‘micronutrients’ in this meta-analysis have undergone thorough testing in large randomized clinical trials that showed different results. I am skeptical whether any of the purported benefits of these supplements would be confirmed in a high-quality randomized controlled trial,” he said.

Dr. Nissen added that many of the included studies are low in quality. “I must quote [renowned cardiologist, Dr.] Franz Messerli: ‘A meta-analysis is like making bouillabaisse. ... One rotten fish can spoil the broth.’ This type of analysis does not override high-quality large, randomized trials.”

In the JACC paper, the study investigators note that the American Heart Association now recommends dietary patterns, including the Mediterranean diet and DASH (the Dietary Approach to Stop Hypertension), as preventive or treatment approaches for cardiovascular disease. A common feature of these dietary patterns is that they are low in saturated fat and sodium and rich in micronutrients such as phytochemicals, unsaturated fatty acids, antioxidant vitamins, and minerals.

“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” they note.

They therefore conducted the current systematic review and meta-analyses of all available randomized controlled trials investigating the effect of micronutrients with antioxidant properties on cardiovascular risk factors and events in diverse populations.

The meta-analysis included a total of 884 randomized trials evaluating 27 types of micronutrients among 883,627 participants.

Results showed that supplementation with n-3 fatty acids, n-6 fatty acids, L-arginine, L-citrulline, folic acid, magnesium, zinc, alpha-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin had “moderate-to high-quality evidence” for reducing cardiovascular risk factors.

Specifically, n-3 fatty acid supplementation was linked to reduced rates of cardiovascular mortality (relative risk, 0.93), myocardial infarction (RR, 0.85), and coronary heart disease events (RR, 0.86). Folic acid supplementation was linked to a decreased stroke risk (RR, 0.84) and coenzyme Q10 was associated with a lower rate of all-cause mortality (RR, 0.68).

“The current study represents the first attempt in providing a comprehensive and most up-to-date evidence map that systematically assessed the quality and quantity of all randomized trials linking the effects of a wide variety of micronutrients on cardiovascular risk factors,” the authors say.

“The comprehensive evidence map presented here highlights the importance of micronutrient diversity and the balance of benefits and risks in the design of whole food–based dietary patterns to promote cardiometabolic health, which may require cultural adaptations to apply globally,” they conclude.

Commenting on some of the specific beneficial findings, Dr. Manson said: “I do believe that the marine omega-3s confer heart benefits, but results are not consistent and vary by dose and formulation.”

However, she pointed out that, regarding folic acid, a previous meta-analysis including eight large randomized trials in more than 37,000 participants found no reduction in coronary events, stroke, or major cardiovascular events with folic acid supplementation, compared with placebo, “so the reported stroke benefit would need further confirmation.”

In an accompanying editorial, Juan Gormaz, PhD, University of Chile, and Rodrigo Carrasco, MD, Chilean Society of Cardiology and Cardiovascular Surgery, both in Santiago, state: “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as n-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The editorialists note that from a research point of view, “although the current information opens interesting perspectives for future consolidation of some antioxidants in preventive cardiology, there is still a long way to go in terms of generating evidence.”

They add that the challenge now for some compounds is to begin establishing consensus in definitions of dose and combinations, as well as continue strengthening the evidence of effectiveness.

“Regarding routine clinical practice, these results begin to open spaces for the integration of new tools into the therapeutic arsenal aimed at cardiovascular prevention in selected populations, which could be easily accessible and, with specific exceptions, would present a low frequency of adverse effects,” they conclude.

This work was partly supported by the United States’ Fulbright Program and by the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund, and the Beijing Municipal Natural Science Foundation.

Dr. Liu has received honoraria for scientific presentations or reviews at Johns Hopkins University, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences, and the National Institutes of Health; he is a member of the Data Safety and Monitoring Board for several trials, including the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial sponsored by Novo Nordisk and a trial of pulmonary hypertension in diabetes patients sponsored by Massachusetts General Hospital; he has received royalties from UpToDate and has received an honorarium from the American Society for Nutrition for his duties as Associate Editor. Co-author Jeffrey Mechanick, MD, has received honoraria from Abbott Nutrition for lectures and serves on the advisory boards of Aveta.Life, L-Nutra, and Twin Health. The other authors report no relevant financial relationships.

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

A new meta-analysis of 884 studies evaluating 27 different types of antioxidant supplements has suggested that some of these micronutrients – including omega-3 fatty acids, folic acid, and coenzyme Q10 – may produce significant cardiovascular benefits.

Other antioxidant supplements that showed some evidence of reducing cardiovascular risk were omega-6 fatty acids, L-arginine, L-citrulline, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

No effect was seen with vitamin C, vitamin D, vitamin E, or selenium, and beta-carotene supplementation was linked to an increase in all-cause mortality in the analysis.

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

“Our systematic assessment and quantification of multiple differential effects of a wide variety of micronutrients and phytochemicals on cardiometabolic health indicate that an optimal nutritional strategy to promote cardiometabolic health will likely involve personalized combinations of these nutrients,” the authors, led by Peng An, PhD, China Agricultural University, Beijing, conclude.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” senior author Simin Liu, MD, professor of epidemiology and medicine at Brown University, Providence, R.I., said in an American College of Cardiology press release.

“The micronutrients identified require further validation in large, high-quality interventional trials to establish clinical efficacy to determine their long-term balance of risks and benefits,” the authors add.
 

Experts cautious

Experts in the field of cardiovascular risk and preventative medicine have urged caution in interpreting these results.

JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, told this news organization that she has concerns that some of the results in the meta-analysis may be inflated by publication bias and some are chance findings that haven’t been well replicated.

“Although this meta-analysis of micronutrients and cardiometabolic health was based on randomized clinical trials, the quality of randomized trials on this subject varies widely,” she noted.

“The study is informative, but the conclusions are only as good as the quality of the evidence. Some of the trials are limited by short duration, and included trials have a wide range of quality, dosing, inclusion criteria, imperfect blinding, and few of them focus on hard clinical events,” Dr. Manson said. “Also, with trials of this nature, the potential for publication bias warrants consideration, because many of the smaller trials with unfavorable or neutral results may remain unpublished or not even be submitted for publication.”   

However, she added, “despite these limitations, this is an important contribution to the literature on micronutrients and health – and goes a long way in separating the wheat from the chaff.”

Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at the Cleveland Clinic, was more critical of the meta-analysis.

“This study does not make sense. Some of the ‘micronutrients’ in this meta-analysis have undergone thorough testing in large randomized clinical trials that showed different results. I am skeptical whether any of the purported benefits of these supplements would be confirmed in a high-quality randomized controlled trial,” he said.

Dr. Nissen added that many of the included studies are low in quality. “I must quote [renowned cardiologist, Dr.] Franz Messerli: ‘A meta-analysis is like making bouillabaisse. ... One rotten fish can spoil the broth.’ This type of analysis does not override high-quality large, randomized trials.”

In the JACC paper, the study investigators note that the American Heart Association now recommends dietary patterns, including the Mediterranean diet and DASH (the Dietary Approach to Stop Hypertension), as preventive or treatment approaches for cardiovascular disease. A common feature of these dietary patterns is that they are low in saturated fat and sodium and rich in micronutrients such as phytochemicals, unsaturated fatty acids, antioxidant vitamins, and minerals.

“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” they note.

They therefore conducted the current systematic review and meta-analyses of all available randomized controlled trials investigating the effect of micronutrients with antioxidant properties on cardiovascular risk factors and events in diverse populations.

The meta-analysis included a total of 884 randomized trials evaluating 27 types of micronutrients among 883,627 participants.

Results showed that supplementation with n-3 fatty acids, n-6 fatty acids, L-arginine, L-citrulline, folic acid, magnesium, zinc, alpha-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin had “moderate-to high-quality evidence” for reducing cardiovascular risk factors.

Specifically, n-3 fatty acid supplementation was linked to reduced rates of cardiovascular mortality (relative risk, 0.93), myocardial infarction (RR, 0.85), and coronary heart disease events (RR, 0.86). Folic acid supplementation was linked to a decreased stroke risk (RR, 0.84) and coenzyme Q10 was associated with a lower rate of all-cause mortality (RR, 0.68).

“The current study represents the first attempt in providing a comprehensive and most up-to-date evidence map that systematically assessed the quality and quantity of all randomized trials linking the effects of a wide variety of micronutrients on cardiovascular risk factors,” the authors say.

“The comprehensive evidence map presented here highlights the importance of micronutrient diversity and the balance of benefits and risks in the design of whole food–based dietary patterns to promote cardiometabolic health, which may require cultural adaptations to apply globally,” they conclude.

Commenting on some of the specific beneficial findings, Dr. Manson said: “I do believe that the marine omega-3s confer heart benefits, but results are not consistent and vary by dose and formulation.”

However, she pointed out that, regarding folic acid, a previous meta-analysis including eight large randomized trials in more than 37,000 participants found no reduction in coronary events, stroke, or major cardiovascular events with folic acid supplementation, compared with placebo, “so the reported stroke benefit would need further confirmation.”

In an accompanying editorial, Juan Gormaz, PhD, University of Chile, and Rodrigo Carrasco, MD, Chilean Society of Cardiology and Cardiovascular Surgery, both in Santiago, state: “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as n-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The editorialists note that from a research point of view, “although the current information opens interesting perspectives for future consolidation of some antioxidants in preventive cardiology, there is still a long way to go in terms of generating evidence.”

They add that the challenge now for some compounds is to begin establishing consensus in definitions of dose and combinations, as well as continue strengthening the evidence of effectiveness.

“Regarding routine clinical practice, these results begin to open spaces for the integration of new tools into the therapeutic arsenal aimed at cardiovascular prevention in selected populations, which could be easily accessible and, with specific exceptions, would present a low frequency of adverse effects,” they conclude.

This work was partly supported by the United States’ Fulbright Program and by the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund, and the Beijing Municipal Natural Science Foundation.

Dr. Liu has received honoraria for scientific presentations or reviews at Johns Hopkins University, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences, and the National Institutes of Health; he is a member of the Data Safety and Monitoring Board for several trials, including the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial sponsored by Novo Nordisk and a trial of pulmonary hypertension in diabetes patients sponsored by Massachusetts General Hospital; he has received royalties from UpToDate and has received an honorarium from the American Society for Nutrition for his duties as Associate Editor. Co-author Jeffrey Mechanick, MD, has received honoraria from Abbott Nutrition for lectures and serves on the advisory boards of Aveta.Life, L-Nutra, and Twin Health. The other authors report no relevant financial relationships.

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

A new meta-analysis of 884 studies evaluating 27 different types of antioxidant supplements has suggested that some of these micronutrients – including omega-3 fatty acids, folic acid, and coenzyme Q10 – may produce significant cardiovascular benefits.

Other antioxidant supplements that showed some evidence of reducing cardiovascular risk were omega-6 fatty acids, L-arginine, L-citrulline, magnesium, zinc, alpha-lipoic acid, melatonin, catechin, curcumin, flavanol, genistein, and quercetin.

No effect was seen with vitamin C, vitamin D, vitamin E, or selenium, and beta-carotene supplementation was linked to an increase in all-cause mortality in the analysis.

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

“Our systematic assessment and quantification of multiple differential effects of a wide variety of micronutrients and phytochemicals on cardiometabolic health indicate that an optimal nutritional strategy to promote cardiometabolic health will likely involve personalized combinations of these nutrients,” the authors, led by Peng An, PhD, China Agricultural University, Beijing, conclude.

“Identifying the optimal mixture of micronutrients is important, as not all are beneficial, and some may even have harmful effects,” senior author Simin Liu, MD, professor of epidemiology and medicine at Brown University, Providence, R.I., said in an American College of Cardiology press release.

“The micronutrients identified require further validation in large, high-quality interventional trials to establish clinical efficacy to determine their long-term balance of risks and benefits,” the authors add.
 

Experts cautious

Experts in the field of cardiovascular risk and preventative medicine have urged caution in interpreting these results.

JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, told this news organization that she has concerns that some of the results in the meta-analysis may be inflated by publication bias and some are chance findings that haven’t been well replicated.

“Although this meta-analysis of micronutrients and cardiometabolic health was based on randomized clinical trials, the quality of randomized trials on this subject varies widely,” she noted.

“The study is informative, but the conclusions are only as good as the quality of the evidence. Some of the trials are limited by short duration, and included trials have a wide range of quality, dosing, inclusion criteria, imperfect blinding, and few of them focus on hard clinical events,” Dr. Manson said. “Also, with trials of this nature, the potential for publication bias warrants consideration, because many of the smaller trials with unfavorable or neutral results may remain unpublished or not even be submitted for publication.”   

However, she added, “despite these limitations, this is an important contribution to the literature on micronutrients and health – and goes a long way in separating the wheat from the chaff.”

Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at the Cleveland Clinic, was more critical of the meta-analysis.

“This study does not make sense. Some of the ‘micronutrients’ in this meta-analysis have undergone thorough testing in large randomized clinical trials that showed different results. I am skeptical whether any of the purported benefits of these supplements would be confirmed in a high-quality randomized controlled trial,” he said.

Dr. Nissen added that many of the included studies are low in quality. “I must quote [renowned cardiologist, Dr.] Franz Messerli: ‘A meta-analysis is like making bouillabaisse. ... One rotten fish can spoil the broth.’ This type of analysis does not override high-quality large, randomized trials.”

In the JACC paper, the study investigators note that the American Heart Association now recommends dietary patterns, including the Mediterranean diet and DASH (the Dietary Approach to Stop Hypertension), as preventive or treatment approaches for cardiovascular disease. A common feature of these dietary patterns is that they are low in saturated fat and sodium and rich in micronutrients such as phytochemicals, unsaturated fatty acids, antioxidant vitamins, and minerals.

“To personalize cardiometabolic preventive and therapeutic dietary practices, it is of critical importance to have a comprehensive and in-depth understanding of the balance of benefits and risks associated with constituent micronutrients in diverse dietary patterns,” they note.

They therefore conducted the current systematic review and meta-analyses of all available randomized controlled trials investigating the effect of micronutrients with antioxidant properties on cardiovascular risk factors and events in diverse populations.

The meta-analysis included a total of 884 randomized trials evaluating 27 types of micronutrients among 883,627 participants.

Results showed that supplementation with n-3 fatty acids, n-6 fatty acids, L-arginine, L-citrulline, folic acid, magnesium, zinc, alpha-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin had “moderate-to high-quality evidence” for reducing cardiovascular risk factors.

Specifically, n-3 fatty acid supplementation was linked to reduced rates of cardiovascular mortality (relative risk, 0.93), myocardial infarction (RR, 0.85), and coronary heart disease events (RR, 0.86). Folic acid supplementation was linked to a decreased stroke risk (RR, 0.84) and coenzyme Q10 was associated with a lower rate of all-cause mortality (RR, 0.68).

“The current study represents the first attempt in providing a comprehensive and most up-to-date evidence map that systematically assessed the quality and quantity of all randomized trials linking the effects of a wide variety of micronutrients on cardiovascular risk factors,” the authors say.

“The comprehensive evidence map presented here highlights the importance of micronutrient diversity and the balance of benefits and risks in the design of whole food–based dietary patterns to promote cardiometabolic health, which may require cultural adaptations to apply globally,” they conclude.

Commenting on some of the specific beneficial findings, Dr. Manson said: “I do believe that the marine omega-3s confer heart benefits, but results are not consistent and vary by dose and formulation.”

However, she pointed out that, regarding folic acid, a previous meta-analysis including eight large randomized trials in more than 37,000 participants found no reduction in coronary events, stroke, or major cardiovascular events with folic acid supplementation, compared with placebo, “so the reported stroke benefit would need further confirmation.”

In an accompanying editorial, Juan Gormaz, PhD, University of Chile, and Rodrigo Carrasco, MD, Chilean Society of Cardiology and Cardiovascular Surgery, both in Santiago, state: “Given that the compounds with more pleiotropic properties produced the better outcomes, the antioxidant paradigm on cardiovascular prevention can be challenged. For example, inasmuch as n-3 fatty acids have antiplatelet and anti-inflammatory properties, they are too complex to enable attribution of the observed benefits solely to their antioxidant capacity.”

The editorialists note that from a research point of view, “although the current information opens interesting perspectives for future consolidation of some antioxidants in preventive cardiology, there is still a long way to go in terms of generating evidence.”

They add that the challenge now for some compounds is to begin establishing consensus in definitions of dose and combinations, as well as continue strengthening the evidence of effectiveness.

“Regarding routine clinical practice, these results begin to open spaces for the integration of new tools into the therapeutic arsenal aimed at cardiovascular prevention in selected populations, which could be easily accessible and, with specific exceptions, would present a low frequency of adverse effects,” they conclude.

This work was partly supported by the United States’ Fulbright Program and by the Beijing Advanced Innovation Center for Food Nutrition and Human Health, the National Natural Science Foundation of China, the Chinese Universities Scientific Fund, and the Beijing Municipal Natural Science Foundation.

Dr. Liu has received honoraria for scientific presentations or reviews at Johns Hopkins University, Fred Hutchinson Cancer Center, Harvard University, University of Buffalo, Guangdong General Hospital, Fuwai Hospital, Chinese Academy of Medical Sciences, and the National Institutes of Health; he is a member of the Data Safety and Monitoring Board for several trials, including the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial sponsored by Novo Nordisk and a trial of pulmonary hypertension in diabetes patients sponsored by Massachusetts General Hospital; he has received royalties from UpToDate and has received an honorarium from the American Society for Nutrition for his duties as Associate Editor. Co-author Jeffrey Mechanick, MD, has received honoraria from Abbott Nutrition for lectures and serves on the advisory boards of Aveta.Life, L-Nutra, and Twin Health. The other authors report no relevant financial relationships.

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