CAD & Atherosclerosis

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A new decision pathway for the management of hypertriglyceridemia, prompted by a large and growing body of evidence that elevated triglycerides to a targetable risk factor for atherosclerotic cardiovascular disease (ASCVD), has been issued by the American College of Cardiology.

According to the chairman of the writing committee, Salim S. Virani, MD, PhD, the recommendations amplify and update more than alter the hypertriglyceridemia treatment recommendations in the 2018 joint multisociety blood cholesterol guidelines issued in 2018.

This decision pathway, however, is focused on triglycerides alone.

“The previous guidelines included a section on strategies for addressing hypertriglyceridemia to reduce ASCVD risk, but this new decision pathway builds on the recommendations with more details and with additional information,” explained Dr. Virani, professor of medicine in the section of cardiovascular research, Baylor College of Medicine, Houston.

Within this newly published document, the definitions of hypertriglyceridemia and rationale for treatment are followed by detailed algorithms for four specific patient groups with varying triglyceride levels:

• Adults with ASCVD.
• Adults at least 40 years of age with diabetes but no ASCVD.
• Adults at least 20 years of age with no ASCVD or diabetes.
• Adults at least 20 years of age with severe hypertriglyceridemia.

“In the design of these algorithms, we made an active effort to make them suitable for use by primary care physicians as well as specialists,” said Dr. Virani. Despite “lots of boxes and arrows,” the flowcharts for each of these patient groups permit clinicians to follow the decision pathway without having to reread the text.

The common emphasis in all four algorithms is to begin by evaluating patients for secondary causes of hypertriglyceridemia, such as multifactorial chylomicronemia syndrome and other diseases associated with elevated triglycerides. The next steps, also common to all algorithms, are to optimize diet and lifestyle changes that lower triglycerides, optimize glycemic control, and optimize statin therapy.

“Although commonly recognized for their impact on LDL-C, statins also provide a 10%-30% dose-dependent reduction in triglycerides in patients with elevated levels,” the guidelines state. Statins are considered a fundamental step to secondary prevention of ASCVD regardless of triglyceride levels.

Once treatable causes or contributors to hypertriglyceridemia have been addressed, lifestyle interventions and statin therapy have been optimized, pharmacologic therapy directed specifically at control of hypertriglyceridemia “can be considered” in those at highest risk of ASCVD events, but Dr. Virani explained that this is never an early or first step in control of elevated triglycerides.

“The entire working group agreed that lifestyle interventions should be highlighted front and center before considering any other intervention,” Dr. Virani explained.

Pharmacologic therapy for hypertriglyceridemia is not ignored. Prescription omega-3 fatty acid products are preferred over nonprescription dietary supplements, which may vary in quality and purity. But these products, rather than a standalone solution, are best applied within the context of efforts to improve diet, lower body weight, and increase physical activity.

Several trials have associated ethyl ester and carboxylic acid preparations with meaningful reductions in triglycerides, but these drugs, including icosapent ethyl (IPE), are not without adverse events. In the pivotal REDUCE-IT trial, IPE was linked with an increased risk of atrial fibrillation relative to placebo.

IPE is “the best option” and the only therapy with an indication for reduction in ASCVD risk, according to Dr. Virani, but he explained that safety concerns led the authors of the new decision pathway to employ cautious language in regard to its use, suggesting that it be “considered” in high-risk patients after other methods of lowering triglycerides have been optimized.

In the algorithm for the four different risk groups, the decision pathways follow stratifications for different levels of hypertriglyceridemia (defined under fasting and nonfasting conditions) and also for specific levels of LDL cholesterol. ASCVD risk assessment is also a factor in determining the next steps along the decision pathway.

According to Michael Davidson, MD, director of the lipid clinic at the University of Chicago, the emphasis on lifestyle changes for hypertriglyceridemia and the prudent language in regard to pharmacologic therapy is appropriate.

“In light of the controversies regarding the REDUCE-IT trial, the writing committee has done a nice job with providing useful guidance regarding the utilization of icosapent ethyl in higher risk patients,” Dr. Davidson said.

Calling the ACC decision pathway “a welcome enhancement of the 2018 ACC/AHA cholesterol guidelines,” Dr. Davidson praised the way in which the limitations of the evidence regarding pharmacologic therapies were explained.

“Most importantly, this decision pathway helps clinicians appreciate that hypertriglyceridemia can be best managed with lifestyle changes and addressing potential secondary causes,” Dr. Davidson said.

Dr. Virani reports no potential conflicts of interest. Dr. Davidson reports financial relationships with multiple pharmaceutical companies including those making or pursuing therapies for control of hypertriglyceridemia.

A study from Japan suggests that a history of cardiovascular events in a spouse may elevate risk for future CV events in the other partner, with one caveat: Men in the cohort study were at increased risk if their wives had such a history, but the association was only one way. The risk of events didn’t go up for women with husbands who had previously experienced a CV event.

byryo/iStock/Getty Images Plus

The results highlight the need for clinicians to screen and possibly intervene with a primary CV prevention strategy “not only first-degree relatives but also spouses with a history of cardiovascular disease,” which is not currently part of the primary prevention guidelines, Hiroyuki Ohbe, MD, University of Tokyo, told this news organization.

In their study published online July 9 in Circulation: Cardiovascular Quality and Outcomes, Dr. Ohbe and Hideo Yasunaga, MD, PhD, of the same institution, assessed the risk of subsequent CV events in adults with a spouse who had experienced a stroke of any kind or had clinical ischemic heart disease such as angina or myocardial infarction.

Johanna Contreras, MD, director of heart failure at Mount Sinai Health System in New York, is not surprised by the finding that a wife’s CV history is linked to the CV risk in the husband.

“I see this often in my practice. When you live with someone, you also behave in a similar way as the other person,” Dr. Contreras told this news organization. “For example, couples who live together are likely to both exercise and have a healthy diet and not smoke.”

And most notably, she said, “the women are usually the ones who drive the healthy behaviors in the family; they watch what the family eats, where they eat, when they eat, and the men tend to allow the women to guide this behavior.”

Dr. Ohbe and Dr. Yasunaga agree, proposing that different results for men and women in the analysis may be because of the dependence of working-aged men on their wives for major aspects of lifestyle, such as diet and exercise. Moreover, they write, increased psychological and physical stress from taking care of a spouse with CV disease may also play a role, as caregivers often neglect their own health.

The team identified 13,759 adults in a large administrative database with no history of CV disease whose spouse had such a history at their first health checkup; they were the exposure group. The team matched each of them with up to four individuals (n = 55,027) who had no CV disease history and spouses without CV disease at their first health checkup; they were the nonexposure group.

The mean observation period was 7.9 years from the first health checkup, at which the subjects’ mean age was 56 years. During the follow-up, more people in the exposure group than the nonexposure group had a history of CV events, 0.6% versus 0.4%.

In the overall cohort, the hazard ratio for future severe CV events – heart failure hospitalization or MI – in those with spouses with a history of CV disease was 1.48 (95% confidence interval, 1.15-1.90).

When stratified by sex, men whose wives had CV disease showed a significantly increased risk of a future severe CV event (HR, 1.68; 95% CI, 1.22-2.32). But women with husbands with CV disease did not (HR, 1.22; 95% CI, 0.82-1.83).

The results of all four sensitivity analyses were similar to those of the primary analysis, both in the overall cohort and in the cohorts stratified by sex. The investigators performed multivariate survival analyses: one that excluded people whose partners had died, one that included death by any cause as an outcome, and one with propensity score matching.

Further studies are needed to confirm their observations and test whether a primary prevention strategy targeted at married couples could reduce CV events, note Dr. Ohbe and Dr. Yasunaga.

The findings have implications for everyday clinical practice, Dr. Contreras said. “When I see a patient who is married and has had a heart attack, I will insist on seeing the partner as well, and I will counsel them on working together to change their lifestyle,” she said in an interview.

“Often when you have that discussion with the couple after one has a heart attack, they quit smoking together, they go the gym together, and they get healthier together,” she said. “That’s now a very important conversation we have before they leave the hospital.”

The study was supported by grants from the Japan Ministry of Health, Ministry of Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. Dr. Ohbe, Dr. Yasunaga, and Dr. Contreras have disclosed no relevant financial relationships.

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

A study from Japan suggests that a history of cardiovascular events in a spouse may elevate risk for future CV events in the other partner, with one caveat: Men in the cohort study were at increased risk if their wives had such a history, but the association was only one way. The risk of events didn’t go up for women with husbands who had previously experienced a CV event.

byryo/iStock/Getty Images Plus

The results highlight the need for clinicians to screen and possibly intervene with a primary CV prevention strategy “not only first-degree relatives but also spouses with a history of cardiovascular disease,” which is not currently part of the primary prevention guidelines, Hiroyuki Ohbe, MD, University of Tokyo, told this news organization.

In their study published online July 9 in Circulation: Cardiovascular Quality and Outcomes, Dr. Ohbe and Hideo Yasunaga, MD, PhD, of the same institution, assessed the risk of subsequent CV events in adults with a spouse who had experienced a stroke of any kind or had clinical ischemic heart disease such as angina or myocardial infarction.

Johanna Contreras, MD, director of heart failure at Mount Sinai Health System in New York, is not surprised by the finding that a wife’s CV history is linked to the CV risk in the husband.

“I see this often in my practice. When you live with someone, you also behave in a similar way as the other person,” Dr. Contreras told this news organization. “For example, couples who live together are likely to both exercise and have a healthy diet and not smoke.”

And most notably, she said, “the women are usually the ones who drive the healthy behaviors in the family; they watch what the family eats, where they eat, when they eat, and the men tend to allow the women to guide this behavior.”

Dr. Ohbe and Dr. Yasunaga agree, proposing that different results for men and women in the analysis may be because of the dependence of working-aged men on their wives for major aspects of lifestyle, such as diet and exercise. Moreover, they write, increased psychological and physical stress from taking care of a spouse with CV disease may also play a role, as caregivers often neglect their own health.

The team identified 13,759 adults in a large administrative database with no history of CV disease whose spouse had such a history at their first health checkup; they were the exposure group. The team matched each of them with up to four individuals (n = 55,027) who had no CV disease history and spouses without CV disease at their first health checkup; they were the nonexposure group.

The mean observation period was 7.9 years from the first health checkup, at which the subjects’ mean age was 56 years. During the follow-up, more people in the exposure group than the nonexposure group had a history of CV events, 0.6% versus 0.4%.

In the overall cohort, the hazard ratio for future severe CV events – heart failure hospitalization or MI – in those with spouses with a history of CV disease was 1.48 (95% confidence interval, 1.15-1.90).

When stratified by sex, men whose wives had CV disease showed a significantly increased risk of a future severe CV event (HR, 1.68; 95% CI, 1.22-2.32). But women with husbands with CV disease did not (HR, 1.22; 95% CI, 0.82-1.83).

The results of all four sensitivity analyses were similar to those of the primary analysis, both in the overall cohort and in the cohorts stratified by sex. The investigators performed multivariate survival analyses: one that excluded people whose partners had died, one that included death by any cause as an outcome, and one with propensity score matching.

Further studies are needed to confirm their observations and test whether a primary prevention strategy targeted at married couples could reduce CV events, note Dr. Ohbe and Dr. Yasunaga.

The findings have implications for everyday clinical practice, Dr. Contreras said. “When I see a patient who is married and has had a heart attack, I will insist on seeing the partner as well, and I will counsel them on working together to change their lifestyle,” she said in an interview.

“Often when you have that discussion with the couple after one has a heart attack, they quit smoking together, they go the gym together, and they get healthier together,” she said. “That’s now a very important conversation we have before they leave the hospital.”

The study was supported by grants from the Japan Ministry of Health, Ministry of Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. Dr. Ohbe, Dr. Yasunaga, and Dr. Contreras have disclosed no relevant financial relationships.

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

A study from Japan suggests that a history of cardiovascular events in a spouse may elevate risk for future CV events in the other partner, with one caveat: Men in the cohort study were at increased risk if their wives had such a history, but the association was only one way. The risk of events didn’t go up for women with husbands who had previously experienced a CV event.

byryo/iStock/Getty Images Plus

The results highlight the need for clinicians to screen and possibly intervene with a primary CV prevention strategy “not only first-degree relatives but also spouses with a history of cardiovascular disease,” which is not currently part of the primary prevention guidelines, Hiroyuki Ohbe, MD, University of Tokyo, told this news organization.

In their study published online July 9 in Circulation: Cardiovascular Quality and Outcomes, Dr. Ohbe and Hideo Yasunaga, MD, PhD, of the same institution, assessed the risk of subsequent CV events in adults with a spouse who had experienced a stroke of any kind or had clinical ischemic heart disease such as angina or myocardial infarction.

Johanna Contreras, MD, director of heart failure at Mount Sinai Health System in New York, is not surprised by the finding that a wife’s CV history is linked to the CV risk in the husband.

“I see this often in my practice. When you live with someone, you also behave in a similar way as the other person,” Dr. Contreras told this news organization. “For example, couples who live together are likely to both exercise and have a healthy diet and not smoke.”

And most notably, she said, “the women are usually the ones who drive the healthy behaviors in the family; they watch what the family eats, where they eat, when they eat, and the men tend to allow the women to guide this behavior.”

Dr. Ohbe and Dr. Yasunaga agree, proposing that different results for men and women in the analysis may be because of the dependence of working-aged men on their wives for major aspects of lifestyle, such as diet and exercise. Moreover, they write, increased psychological and physical stress from taking care of a spouse with CV disease may also play a role, as caregivers often neglect their own health.

The team identified 13,759 adults in a large administrative database with no history of CV disease whose spouse had such a history at their first health checkup; they were the exposure group. The team matched each of them with up to four individuals (n = 55,027) who had no CV disease history and spouses without CV disease at their first health checkup; they were the nonexposure group.

The mean observation period was 7.9 years from the first health checkup, at which the subjects’ mean age was 56 years. During the follow-up, more people in the exposure group than the nonexposure group had a history of CV events, 0.6% versus 0.4%.

In the overall cohort, the hazard ratio for future severe CV events – heart failure hospitalization or MI – in those with spouses with a history of CV disease was 1.48 (95% confidence interval, 1.15-1.90).

When stratified by sex, men whose wives had CV disease showed a significantly increased risk of a future severe CV event (HR, 1.68; 95% CI, 1.22-2.32). But women with husbands with CV disease did not (HR, 1.22; 95% CI, 0.82-1.83).

The results of all four sensitivity analyses were similar to those of the primary analysis, both in the overall cohort and in the cohorts stratified by sex. The investigators performed multivariate survival analyses: one that excluded people whose partners had died, one that included death by any cause as an outcome, and one with propensity score matching.

Further studies are needed to confirm their observations and test whether a primary prevention strategy targeted at married couples could reduce CV events, note Dr. Ohbe and Dr. Yasunaga.

The findings have implications for everyday clinical practice, Dr. Contreras said. “When I see a patient who is married and has had a heart attack, I will insist on seeing the partner as well, and I will counsel them on working together to change their lifestyle,” she said in an interview.

“Often when you have that discussion with the couple after one has a heart attack, they quit smoking together, they go the gym together, and they get healthier together,” she said. “That’s now a very important conversation we have before they leave the hospital.”

The study was supported by grants from the Japan Ministry of Health, Ministry of Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. Dr. Ohbe, Dr. Yasunaga, and Dr. Contreras have disclosed no relevant financial relationships.

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

The longer a person has diabetes, the greater their risk for also developing heart failure, according to an analysis of nearly 10,000 U.S. adults followed for a median of close to 23 years.

In a multivariable analysis the rate of incident heart failure increased steadily and significantly as diabetes duration increased. Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49%) who never had diabetes or prediabetes, reported Justin B. Echouffo-Tcheugui, MD, PhD, and coauthors in an article published in JACC Heart Failure.

People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes. People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls, reported Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore.

Similar rates of HFrEF and HFpEF

Among all 1,841 people in the dataset with diabetes for any length of time each additional 5 years of the disorder linked with a significant, relative 17% increase in the rate of incident heart failure. Incidence of heart failure rose even more sharply with added duration among those with a hemoglobin A1c of 7% or greater, compared with those with better glycemic control. And the rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

The study dataset included 9,734 adults enrolled into the Atherosclerosis Risk in Communities (ARIC) study, and during a median follow-up of 22.5 years they had nearly 2,000 episodes of either hospitalization or death secondary to incident heart failure. This included 617 (31%) events involving HFpEF, 495 events (25%) involving HFrEF, and 876 unclassified heart failure events.

The cohort averaged 63 years of age; 58% were women, 23% were Black, and 77% were White (the study design excluded people with other racial and ethnic backgrounds). The study design also excluded people with a history of heart failure or coronary artery disease, as well as those diagnosed with diabetes prior to age 18 resulting in a study group that presumably mostly had type 2 diabetes when diabetes was present. The report provided no data on the specific numbers of patients with type 1 or type 2 diabetes.

“It’s not surprising that a longer duration of diabetes is associated with heart failure, but the etiology remains problematic,” commented Robert H. Eckel, MD, an endocrinologist at the University of Colorado at Denver, Aurora. “The impact of diabetes on incident heart failure is not well know, particularly duration of diabetes,” although disorders often found in patients with diabetes, such as hypertension and diabetic cardiomyopathy, likely have roles in causing heart failure, he said.
 

Diabetes duration may signal need for an SGLT2 inhibitor

“With emerging novel treatments like the SGLT2 [sodium-glucose cotransporter 2] inhibitors for preventing heart failure hospitalizations and deaths in patients with type 2 diabetes, this is a timely analysis,” Dr. Eckel said in an interview.

“There is no question that with increased duration of type 2 diabetes” the need for an agent from the SGLT2-inhibitor class increases. Although, because of the proven protection these drugs give against heart failure events and progression of chronic kidney disease, treatment with this drug class should start early in patients with type 2 diabetes, he added.

Dr. Echouffo-Tcheugui and his coauthors agreed, citing two important clinical take-aways from their findings:

First, interventions that delay the onset of diabetes may potentially reduce incident heart failure; second, patients with diabetes might benefit from cardioprotective treatments such as SGLT2 inhibitors, the report said.

“Our observations suggest the potential prognostic relevance of diabetes duration in assessing heart failure,” the authors wrote. Integrating diabetes duration into heart failure risk estimation in people with diabetes “could help refine the selection of high-risk individuals who may derive the greatest absolute benefit from aggressive cardioprotective therapies such as SGLT2 inhibitors.”

The analysis also identified several other demographic and clinical factors that influenced the relative effect of diabetes duration. Longer duration was linked with higher rates of incident heart failure in women compared with men, in Blacks compared with Whites, in people younger than 65 compared with older people, in people with an A1c of 7% or higher, and in those with a body mass index of 30 kg/m² or greater.

The ARIC study and the analyses run by Dr. Echouffo-Tcheugui and his coauthors received no commercial funding. Dr. Echouffo-Tcheugui and Dr. Eckel had no relevant disclosures.

[email protected]

The longer a person has diabetes, the greater their risk for also developing heart failure, according to an analysis of nearly 10,000 U.S. adults followed for a median of close to 23 years.

In a multivariable analysis the rate of incident heart failure increased steadily and significantly as diabetes duration increased. Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49%) who never had diabetes or prediabetes, reported Justin B. Echouffo-Tcheugui, MD, PhD, and coauthors in an article published in JACC Heart Failure.

People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes. People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls, reported Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore.

Similar rates of HFrEF and HFpEF

Among all 1,841 people in the dataset with diabetes for any length of time each additional 5 years of the disorder linked with a significant, relative 17% increase in the rate of incident heart failure. Incidence of heart failure rose even more sharply with added duration among those with a hemoglobin A1c of 7% or greater, compared with those with better glycemic control. And the rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

The study dataset included 9,734 adults enrolled into the Atherosclerosis Risk in Communities (ARIC) study, and during a median follow-up of 22.5 years they had nearly 2,000 episodes of either hospitalization or death secondary to incident heart failure. This included 617 (31%) events involving HFpEF, 495 events (25%) involving HFrEF, and 876 unclassified heart failure events.

The cohort averaged 63 years of age; 58% were women, 23% were Black, and 77% were White (the study design excluded people with other racial and ethnic backgrounds). The study design also excluded people with a history of heart failure or coronary artery disease, as well as those diagnosed with diabetes prior to age 18 resulting in a study group that presumably mostly had type 2 diabetes when diabetes was present. The report provided no data on the specific numbers of patients with type 1 or type 2 diabetes.

“It’s not surprising that a longer duration of diabetes is associated with heart failure, but the etiology remains problematic,” commented Robert H. Eckel, MD, an endocrinologist at the University of Colorado at Denver, Aurora. “The impact of diabetes on incident heart failure is not well know, particularly duration of diabetes,” although disorders often found in patients with diabetes, such as hypertension and diabetic cardiomyopathy, likely have roles in causing heart failure, he said.
 

Diabetes duration may signal need for an SGLT2 inhibitor

“With emerging novel treatments like the SGLT2 [sodium-glucose cotransporter 2] inhibitors for preventing heart failure hospitalizations and deaths in patients with type 2 diabetes, this is a timely analysis,” Dr. Eckel said in an interview.

“There is no question that with increased duration of type 2 diabetes” the need for an agent from the SGLT2-inhibitor class increases. Although, because of the proven protection these drugs give against heart failure events and progression of chronic kidney disease, treatment with this drug class should start early in patients with type 2 diabetes, he added.

Dr. Echouffo-Tcheugui and his coauthors agreed, citing two important clinical take-aways from their findings:

First, interventions that delay the onset of diabetes may potentially reduce incident heart failure; second, patients with diabetes might benefit from cardioprotective treatments such as SGLT2 inhibitors, the report said.

“Our observations suggest the potential prognostic relevance of diabetes duration in assessing heart failure,” the authors wrote. Integrating diabetes duration into heart failure risk estimation in people with diabetes “could help refine the selection of high-risk individuals who may derive the greatest absolute benefit from aggressive cardioprotective therapies such as SGLT2 inhibitors.”

The analysis also identified several other demographic and clinical factors that influenced the relative effect of diabetes duration. Longer duration was linked with higher rates of incident heart failure in women compared with men, in Blacks compared with Whites, in people younger than 65 compared with older people, in people with an A1c of 7% or higher, and in those with a body mass index of 30 kg/m² or greater.

The ARIC study and the analyses run by Dr. Echouffo-Tcheugui and his coauthors received no commercial funding. Dr. Echouffo-Tcheugui and Dr. Eckel had no relevant disclosures.

[email protected]

The longer a person has diabetes, the greater their risk for also developing heart failure, according to an analysis of nearly 10,000 U.S. adults followed for a median of close to 23 years.

In a multivariable analysis the rate of incident heart failure increased steadily and significantly as diabetes duration increased. Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49%) who never had diabetes or prediabetes, reported Justin B. Echouffo-Tcheugui, MD, PhD, and coauthors in an article published in JACC Heart Failure.

People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes. People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls, reported Dr. Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore.

Similar rates of HFrEF and HFpEF

Among all 1,841 people in the dataset with diabetes for any length of time each additional 5 years of the disorder linked with a significant, relative 17% increase in the rate of incident heart failure. Incidence of heart failure rose even more sharply with added duration among those with a hemoglobin A1c of 7% or greater, compared with those with better glycemic control. And the rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

The study dataset included 9,734 adults enrolled into the Atherosclerosis Risk in Communities (ARIC) study, and during a median follow-up of 22.5 years they had nearly 2,000 episodes of either hospitalization or death secondary to incident heart failure. This included 617 (31%) events involving HFpEF, 495 events (25%) involving HFrEF, and 876 unclassified heart failure events.

The cohort averaged 63 years of age; 58% were women, 23% were Black, and 77% were White (the study design excluded people with other racial and ethnic backgrounds). The study design also excluded people with a history of heart failure or coronary artery disease, as well as those diagnosed with diabetes prior to age 18 resulting in a study group that presumably mostly had type 2 diabetes when diabetes was present. The report provided no data on the specific numbers of patients with type 1 or type 2 diabetes.

“It’s not surprising that a longer duration of diabetes is associated with heart failure, but the etiology remains problematic,” commented Robert H. Eckel, MD, an endocrinologist at the University of Colorado at Denver, Aurora. “The impact of diabetes on incident heart failure is not well know, particularly duration of diabetes,” although disorders often found in patients with diabetes, such as hypertension and diabetic cardiomyopathy, likely have roles in causing heart failure, he said.
 

Diabetes duration may signal need for an SGLT2 inhibitor

“With emerging novel treatments like the SGLT2 [sodium-glucose cotransporter 2] inhibitors for preventing heart failure hospitalizations and deaths in patients with type 2 diabetes, this is a timely analysis,” Dr. Eckel said in an interview.

“There is no question that with increased duration of type 2 diabetes” the need for an agent from the SGLT2-inhibitor class increases. Although, because of the proven protection these drugs give against heart failure events and progression of chronic kidney disease, treatment with this drug class should start early in patients with type 2 diabetes, he added.

Dr. Echouffo-Tcheugui and his coauthors agreed, citing two important clinical take-aways from their findings:

First, interventions that delay the onset of diabetes may potentially reduce incident heart failure; second, patients with diabetes might benefit from cardioprotective treatments such as SGLT2 inhibitors, the report said.

“Our observations suggest the potential prognostic relevance of diabetes duration in assessing heart failure,” the authors wrote. Integrating diabetes duration into heart failure risk estimation in people with diabetes “could help refine the selection of high-risk individuals who may derive the greatest absolute benefit from aggressive cardioprotective therapies such as SGLT2 inhibitors.”

The analysis also identified several other demographic and clinical factors that influenced the relative effect of diabetes duration. Longer duration was linked with higher rates of incident heart failure in women compared with men, in Blacks compared with Whites, in people younger than 65 compared with older people, in people with an A1c of 7% or higher, and in those with a body mass index of 30 kg/m² or greater.

The ARIC study and the analyses run by Dr. Echouffo-Tcheugui and his coauthors received no commercial funding. Dr. Echouffo-Tcheugui and Dr. Eckel had no relevant disclosures.

[email protected]

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

About 87% of Texas physicians reported a “drastic increase over the past 5 years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association, said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says: ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to reengage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said: “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are “an important way” to deliver “safe, high-quality care” to patients, she added.
 

Potential for harm?

Sadeea Abbasi, MD, a practicing physician at Cedars-Sinai in the gastroenterology clinical office in Santa Monica, Calif., can attest that these practices are harmful for her patients.

“Prior authorization requirements have been on the rise across various medical specialties. For GI, we have seen an increase of required approvals for procedures like upper endoscopy, colonoscopy, and wireless capsule endoscopy and in medications prescribed, including biologic infusions for inflammatory bowel disease.”

Dr. Abbasi added: “One of the largest concerns I have with this growing ‘cost-savings’ trend is the impact it has on clinical outcomes. I have seen patients suffer with symptoms while waiting for a decision on a prior authorization for a medication. My patients have endured confusion and chaos when arriving for imaging appointments, only to learn the insurance has not reached a decision on whether the study is approved. When patients learn their procedure has been delayed, they have to reschedule the appointment, take another day off work, coordinate transportation and most importantly, postpone subsequent treatments to alleviate symptoms.”

According to an AMA survey, almost all physicians (94%) said prior authorization delays care and 79% percent have had patients abandon their recommended treatment because of issues related to prior authorization. This delay causes potentially irreversible damage to patients’ digestive system and increases the likelihood of hospitalization. This is a huge issue for America’s seniors: Medicare Advantage (MA) plans, which represent 24.1 million of the 62 million Medicare beneficiaries, the increase in prior authorization requests has been substantial.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA and nearly 300 other stakeholders, including the American Gastroenterological Association, support the Improving Seniors’ Timely Access to Care Act (H.R. 3173). The legislation includes a provision related to “gold carding,” said Robert Mills, an AMA spokesperson.

The bill aims to establish transparency requirements and standards for prior authorization processes related to MA plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Ensuring prior authorization requests are reviewed by qualified medical personnel.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

This legislation was introduced in the U.S. House of Representatives in May by representatives Suzan DelBene (D-Wash.); Mike Kelly (R-Pa.); Ami Bera, MD (D-Calif.); and Larry Bucshon (R-Ind.), after which it was referred to the House Committee on Energy and Commerce and the House Committee on Ways and Means for consideration.

Gaining support for this legislation is a priority for AGA and as such the legislation will be featured as a top policy request at AGA’s upcoming fall Advocacy Day on Sept. 23. The AGA encourages all physicians to contact their lawmakers, urging for support of the bill in the 117th Congress.

In addition to AGA’s advocacy efforts on prior authorization reform, the Regulatory Relief Coalition, a group of national physician specialty organizations, advocates for regulatory burden reduction in Medicare so that physicians can spend more time treating patients. The physician community has banded together to address prior authorization burdens in our field and improve delivery of patient care. Learn more about prior authorization burdens and the various advocacy efforts being pursued.

With additional reporting by staff from this news organization.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

About 87% of Texas physicians reported a “drastic increase over the past 5 years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association, said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says: ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to reengage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said: “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are “an important way” to deliver “safe, high-quality care” to patients, she added.
 

Potential for harm?

Sadeea Abbasi, MD, a practicing physician at Cedars-Sinai in the gastroenterology clinical office in Santa Monica, Calif., can attest that these practices are harmful for her patients.

“Prior authorization requirements have been on the rise across various medical specialties. For GI, we have seen an increase of required approvals for procedures like upper endoscopy, colonoscopy, and wireless capsule endoscopy and in medications prescribed, including biologic infusions for inflammatory bowel disease.”

Dr. Abbasi added: “One of the largest concerns I have with this growing ‘cost-savings’ trend is the impact it has on clinical outcomes. I have seen patients suffer with symptoms while waiting for a decision on a prior authorization for a medication. My patients have endured confusion and chaos when arriving for imaging appointments, only to learn the insurance has not reached a decision on whether the study is approved. When patients learn their procedure has been delayed, they have to reschedule the appointment, take another day off work, coordinate transportation and most importantly, postpone subsequent treatments to alleviate symptoms.”

According to an AMA survey, almost all physicians (94%) said prior authorization delays care and 79% percent have had patients abandon their recommended treatment because of issues related to prior authorization. This delay causes potentially irreversible damage to patients’ digestive system and increases the likelihood of hospitalization. This is a huge issue for America’s seniors: Medicare Advantage (MA) plans, which represent 24.1 million of the 62 million Medicare beneficiaries, the increase in prior authorization requests has been substantial.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA and nearly 300 other stakeholders, including the American Gastroenterological Association, support the Improving Seniors’ Timely Access to Care Act (H.R. 3173). The legislation includes a provision related to “gold carding,” said Robert Mills, an AMA spokesperson.

The bill aims to establish transparency requirements and standards for prior authorization processes related to MA plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Ensuring prior authorization requests are reviewed by qualified medical personnel.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

This legislation was introduced in the U.S. House of Representatives in May by representatives Suzan DelBene (D-Wash.); Mike Kelly (R-Pa.); Ami Bera, MD (D-Calif.); and Larry Bucshon (R-Ind.), after which it was referred to the House Committee on Energy and Commerce and the House Committee on Ways and Means for consideration.

Gaining support for this legislation is a priority for AGA and as such the legislation will be featured as a top policy request at AGA’s upcoming fall Advocacy Day on Sept. 23. The AGA encourages all physicians to contact their lawmakers, urging for support of the bill in the 117th Congress.

In addition to AGA’s advocacy efforts on prior authorization reform, the Regulatory Relief Coalition, a group of national physician specialty organizations, advocates for regulatory burden reduction in Medicare so that physicians can spend more time treating patients. The physician community has banded together to address prior authorization burdens in our field and improve delivery of patient care. Learn more about prior authorization burdens and the various advocacy efforts being pursued.

With additional reporting by staff from this news organization.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

About 87% of Texas physicians reported a “drastic increase over the past 5 years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association, said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says: ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to reengage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said: “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are “an important way” to deliver “safe, high-quality care” to patients, she added.
 

Potential for harm?

Sadeea Abbasi, MD, a practicing physician at Cedars-Sinai in the gastroenterology clinical office in Santa Monica, Calif., can attest that these practices are harmful for her patients.

“Prior authorization requirements have been on the rise across various medical specialties. For GI, we have seen an increase of required approvals for procedures like upper endoscopy, colonoscopy, and wireless capsule endoscopy and in medications prescribed, including biologic infusions for inflammatory bowel disease.”

Dr. Abbasi added: “One of the largest concerns I have with this growing ‘cost-savings’ trend is the impact it has on clinical outcomes. I have seen patients suffer with symptoms while waiting for a decision on a prior authorization for a medication. My patients have endured confusion and chaos when arriving for imaging appointments, only to learn the insurance has not reached a decision on whether the study is approved. When patients learn their procedure has been delayed, they have to reschedule the appointment, take another day off work, coordinate transportation and most importantly, postpone subsequent treatments to alleviate symptoms.”

According to an AMA survey, almost all physicians (94%) said prior authorization delays care and 79% percent have had patients abandon their recommended treatment because of issues related to prior authorization. This delay causes potentially irreversible damage to patients’ digestive system and increases the likelihood of hospitalization. This is a huge issue for America’s seniors: Medicare Advantage (MA) plans, which represent 24.1 million of the 62 million Medicare beneficiaries, the increase in prior authorization requests has been substantial.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA and nearly 300 other stakeholders, including the American Gastroenterological Association, support the Improving Seniors’ Timely Access to Care Act (H.R. 3173). The legislation includes a provision related to “gold carding,” said Robert Mills, an AMA spokesperson.

The bill aims to establish transparency requirements and standards for prior authorization processes related to MA plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Ensuring prior authorization requests are reviewed by qualified medical personnel.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

This legislation was introduced in the U.S. House of Representatives in May by representatives Suzan DelBene (D-Wash.); Mike Kelly (R-Pa.); Ami Bera, MD (D-Calif.); and Larry Bucshon (R-Ind.), after which it was referred to the House Committee on Energy and Commerce and the House Committee on Ways and Means for consideration.

Gaining support for this legislation is a priority for AGA and as such the legislation will be featured as a top policy request at AGA’s upcoming fall Advocacy Day on Sept. 23. The AGA encourages all physicians to contact their lawmakers, urging for support of the bill in the 117th Congress.

In addition to AGA’s advocacy efforts on prior authorization reform, the Regulatory Relief Coalition, a group of national physician specialty organizations, advocates for regulatory burden reduction in Medicare so that physicians can spend more time treating patients. The physician community has banded together to address prior authorization burdens in our field and improve delivery of patient care. Learn more about prior authorization burdens and the various advocacy efforts being pursued.

With additional reporting by staff from this news organization.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

Among patients hospitalized for COVID-19, those who had been taking statins had a substantially lower risk of death in a new large observational study.

Results showed that use of statins prior to admission was linked to a greater than 40% reduction in mortality and a greater than 25% reduction in risk of developing a severe outcome.

The findings come an analysis of data from the American Heart Association’s COVID-19 Cardiovascular Disease Registry on more than 10,000 patients hospitalized with COVID-19 at 104 hospitals across the United States published in PLoS One.

While several other studies have suggested benefits of statins in COVID-19, this is by far the largest study so far on this topic.

“I would say this is the most reliable study on statins in COVID-19 to date, with the results adjusted for many confounders, including socioeconomic factors and insurance type,” lead author Lori B. Daniels, MD, told this news organization. “However, it still an observational study and therefore falls short of a randomized study. But I would think a randomized study of statins in COVID-19 is probably not feasible, so this study provides excellent data at an observational level.”

After propensity matching for cardiovascular disease, results showed that most of the benefit of statins occurred in patients with known cardiovascular disease.

“While most patients taking statins will have cardiovascular disease, there are also many patients who take these drugs who don’t have heart disease but do have cardiovascular risk factors, such as those with raised cholesterol, or a family history of cardiovascular disease. For [such patients], the effect of statins was also in the same direction but it was not significant. This doesn’t exclude an effect,” noted Dr. Daniels, who is professor of medicine and director of cardiovascular intensive care at the University of California, San Diego.

“We are not saying that everyone should rush out and take a statin if they do not have risk factors for cardiovascular in order to lower their risk of dying from COVID. But if individuals do have an indication for a statin and are not taking one of these dugs this is another good reason to start taking them now,” she added.

The investigators embarked on the study because, although previous observational studies have found that statins may reduce the severity of COVID-19 infection, these studies have been limited in size with mostly single-center or regional studies, and some results have been conflicting. They therefore conducted the current, much larger analysis, in the AHA COVID-19 CVD Registry which systematically collected hospitalized patient–level data in a broad and diverse hospital and patient population across the United States.

For the analysis, the researchers analyzed data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 U.S. hospitals enrolled in the AHA registry to evaluate the associations between statin use and outcomes.

Most patients (71%) had either cardiovascular disease, hypertension, or both. Prior to admission, 42% of subjects used statins, with 7% being on statins alone and 35% on statins plus antihypertensives. Death (or discharge to hospice) occurred in 2,212 subjects (21%).

Results showed that outpatient use of statins, either alone or with antihypertensives, was associated with a 41% reduced risk of death (odds ratio, 0.59; 95% confidence interval, 0.50-0.69), after adjusting for demographic characteristics, underlying conditions, insurance status, hospital site, and concurrent medications. Statin use was also associated with a roughly 25% lower adjusted odds of developing severe disease.

Noting that patients on statins are also likely to be on antihypertensive medication, the researchers found that the statin benefit on mortality was seen in both patients taking a statin alone (OR, 0.54) and in those taking statins with an antihypertensive medication (OR, 0.60).

Use of antihypertensive drugs was associated with a smaller, albeit still substantial, 27% lower odds of death (OR, 0.73; 95% CI, 0.62-0.87).

In propensity-matched analyses, use of statins and/or antihypertensives was tied to a 32% reduced risk of death among those with a history of CVD and/or hypertension (OR, 0.68; 95% CI, 0.58-0.81). An observed 16% reduction in odds of death with statins and/or antihypertensive drugs among those without cardiovascular disease and/or hypertension was not statistically significant (OR, 0.84; 95% CI, 0.58-1.22).
 

Stabilizing the underlying disease

The researchers pointed out that the results of the propensity matching analysis are consistent with the hypothesis that the major benefit of these medications accrues from treating and/or stabilizing underlying disease.

“Although it is well known that statins improve long-term outcomes among patients with or at elevated risk for cardiovascular disease, the association with a large short-term benefit which accrues in the setting of hospitalization for COVID-19 is a new and intriguing finding,” they said.

They cited several “plausible mechanisms whereby statins could directly mitigate outcomes in COVID-19 beyond treating underlying disease conditions,” including anti-inflammatory effects and a direct inhibitory effect on the SARS-CoV-2 virus.

Dr. Daniels elaborated more on the potential mechanism at play in an interview: “I think what is happening is that the statin is stabilizing the coronary disease so patients are less likely to die from MI or stroke, and this gives them more time and strength to recover from COVID-19.”

She added: “Statins may also have some direct anti-COVID effects such as an anti-inflammatory actions, but I would guess that this is probably not the primary effect behind what we’re seeing here.”
 

‘Important clinical implications’

The authors say their findings have “important clinical implications.”

They noted that early in the pandemic there was speculation that certain medications, including statins, and the ACE inhibitor/angiotensin receptor blocker (ARB) classes of antihypertensives may confer an increased susceptibility to COVID-19 positivity and/or severity.

“Our study reinforces the AHA and others’ recommendations that not only is it safe to remain on these medications, but they may substantially reduce risk of severe COVID-19 and especially death from COVID-19, particularly statins, and particularly among those with associated underlying conditions,” the authors stressed.

Dr. Daniels added that, although statins are very safe drugs, there are always some patients who prefer not to take medication even if indicated, and others who may have borderline indications and decide not to take a statin at present.

“This study may persuade these patients that taking a statin is the right thing to do. It may give those patients on the cusp of thinking about taking one of these drugs a reason to go ahead,” she said.
 

‘Provocative but not definitive’

Commenting on the study, Robert Harrington, MD, professor of medicine and chair of the department of medicine at Stanford (Calif.) University, said: “These are interesting observational data but as such have all the limitations of nonrandomized comparisons despite the best attempts to adjust for a variety of potential confounders. For example, is this an effect of statins (perhaps through some anti-inflammatory mechanism) or is it more an effect that can be attributed to the patients who are prescribed and taking a statin, compared with those who are not?”

He added: “The primary clinical benefit of statins, based on many large randomized clinical trials, seems to be derived from their LDL lowering effect. Observational studies have suggested potential benefits from anti-inflammatory effects of statins, but the randomized trials have not confirmed these observations. So, the current data are interesting, even provocative, but ultimately hypothesis generating rather than definitive.”

Also commenting on the study, Steven Nissen, MD, professor of medicine at the Cleveland Clinic, said: “While statins have many established benefits, their role in preventing COVID-19 complications is very speculative. Like all observational studies, the current study must be viewed as hypothesis generating, not definitive evidence of benefit. There are many potential confounders. I’m skeptical.”

The authors of this study received no specific funding for this work and report no competing interests. Dr. Harrington was AHA president when the COVID registry was created and he is still a member of the AHA board, which has oversight over the project.

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology.

And regardless of coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.

“The novel risk-enhancing factors are not perfect,” said lead author Jaideep Patel, MD, director of preventive cardiology at Johns Hopkins Heart Center at Greater Baltimore Medical Center. He noted that the 2018 dyslipidemia guidelines suggested the risk for cardiovascular events rises when new risk-enhancing factors emerge, and that it was difficult to predict the extent to which each enhancer could change the 10-year risk. 
 

Utility of CAC

“In this setting, the most significant finding that supports the utility of CAC scoring is when CAC is absent – a CAC of 0 – even in the setting of any of these enhancers, whether it be single or multiple, the 10-year risk remains extremely low – at the very least below the accepted threshold to initiate statin therapy,” Dr. Patel said.

That threshold is below the 7.5% 10-year ASCVD incidence rate. Over the 12-year mean study follow-up, the ASCVD incidence rate among patients with a CAC score of 0 for all risk-enhancing factors was 7.5 events per 1,000 person years, with one exception: ABI had an incidence rate of 10.4 events per 1,000 person years. “A low ABI score should trigger statin initiation irrespective of CAC score,” Dr. Patel said.

The study found a CAC score of 0 in 45.7% of those with one or two risk-enhancing factors versus 40.3% in those with three or more. “Across all the risk enhancers (except low ABI), the prevalence of CAC of 0 was greater than 50% in women; that is, enhancers overestimate risk,” Dr. Patel said. “The prevalence of CAC of 0 was approximately 40% across all risk enhancers; that is, enhancers overestimate risk.”

Dr. Patel said previous studies have suggested the risk of a major cardiovascular event was almost identical for statin and nonstatin users with a CAC score of 0. “If there is uncertainty about statin use after the physician-patient risk discussion,” he said, “CAC scoring may be helpful to guide the use of statin therapy.”

Senior author Mahmoud Al Rifai, MD, MPH, added: “For example, if CAC was absent, a statin could be deprescribed if there’s disutility on the part of the patient, with ongoing lifestyle and risk factor modification efforts.” Dr. Al Rifai is a cardiology fellow at Baylor College of Medicine, Houston.

Dr. Patel said: “Alternatively, if CAC was present, then it would be prudent to continue statin therapy.”

While South Asian ethnicity is a risk enhancing factor, the investigators acknowledged that MESA didn’t recruit this population group.
 

Study confirms guidelines

The study “supports the contention of the [AHA/ACC] guidelines that, in people who are in this intermediate risk range, there may be factors that either favor statin treatment or suggest that statin treatment could be deferred,” said Neil J. Stone, MD, of Northwestern University, Chicago, and author of the 2013 ASCVD risk calculator. “The guidelines pointed out that risk-enhancing factors may be associated with an increase in lifetime risk, not necessarily short term, and so could inform a more personalized risk discussion.”

The study findings validate the utility of CAC for guiding statin therapy, Dr. Stone said. “For those who have felt that a calcium score is not useful,” he said, “this is additional evidence to show that, in the context of making a decision in those at intermediate risk as proposed by the guidelines, a calcium score is indeed very useful.”

Dr. Stone added: “An important clinical point not mentioned by the authors is that, when the patient has a CAC score of 0 and risk factors, this may be exactly the time to be aggressive with lifestyle to prevent them from developing a positive CAC score and atherosclerosis, because once atherosclerosis is present, treatment may not restore the risk back to the original lower state.”

Dr. Patel, Dr. Al Rifai, and Dr. Stone have no relevant relationships to disclose. A number of study coauthors disclosed multiple financial relationships.

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology.

And regardless of coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.

“The novel risk-enhancing factors are not perfect,” said lead author Jaideep Patel, MD, director of preventive cardiology at Johns Hopkins Heart Center at Greater Baltimore Medical Center. He noted that the 2018 dyslipidemia guidelines suggested the risk for cardiovascular events rises when new risk-enhancing factors emerge, and that it was difficult to predict the extent to which each enhancer could change the 10-year risk. 
 

Utility of CAC

“In this setting, the most significant finding that supports the utility of CAC scoring is when CAC is absent – a CAC of 0 – even in the setting of any of these enhancers, whether it be single or multiple, the 10-year risk remains extremely low – at the very least below the accepted threshold to initiate statin therapy,” Dr. Patel said.

That threshold is below the 7.5% 10-year ASCVD incidence rate. Over the 12-year mean study follow-up, the ASCVD incidence rate among patients with a CAC score of 0 for all risk-enhancing factors was 7.5 events per 1,000 person years, with one exception: ABI had an incidence rate of 10.4 events per 1,000 person years. “A low ABI score should trigger statin initiation irrespective of CAC score,” Dr. Patel said.

The study found a CAC score of 0 in 45.7% of those with one or two risk-enhancing factors versus 40.3% in those with three or more. “Across all the risk enhancers (except low ABI), the prevalence of CAC of 0 was greater than 50% in women; that is, enhancers overestimate risk,” Dr. Patel said. “The prevalence of CAC of 0 was approximately 40% across all risk enhancers; that is, enhancers overestimate risk.”

Dr. Patel said previous studies have suggested the risk of a major cardiovascular event was almost identical for statin and nonstatin users with a CAC score of 0. “If there is uncertainty about statin use after the physician-patient risk discussion,” he said, “CAC scoring may be helpful to guide the use of statin therapy.”

Senior author Mahmoud Al Rifai, MD, MPH, added: “For example, if CAC was absent, a statin could be deprescribed if there’s disutility on the part of the patient, with ongoing lifestyle and risk factor modification efforts.” Dr. Al Rifai is a cardiology fellow at Baylor College of Medicine, Houston.

Dr. Patel said: “Alternatively, if CAC was present, then it would be prudent to continue statin therapy.”

While South Asian ethnicity is a risk enhancing factor, the investigators acknowledged that MESA didn’t recruit this population group.
 

Study confirms guidelines

The study “supports the contention of the [AHA/ACC] guidelines that, in people who are in this intermediate risk range, there may be factors that either favor statin treatment or suggest that statin treatment could be deferred,” said Neil J. Stone, MD, of Northwestern University, Chicago, and author of the 2013 ASCVD risk calculator. “The guidelines pointed out that risk-enhancing factors may be associated with an increase in lifetime risk, not necessarily short term, and so could inform a more personalized risk discussion.”

The study findings validate the utility of CAC for guiding statin therapy, Dr. Stone said. “For those who have felt that a calcium score is not useful,” he said, “this is additional evidence to show that, in the context of making a decision in those at intermediate risk as proposed by the guidelines, a calcium score is indeed very useful.”

Dr. Stone added: “An important clinical point not mentioned by the authors is that, when the patient has a CAC score of 0 and risk factors, this may be exactly the time to be aggressive with lifestyle to prevent them from developing a positive CAC score and atherosclerosis, because once atherosclerosis is present, treatment may not restore the risk back to the original lower state.”

Dr. Patel, Dr. Al Rifai, and Dr. Stone have no relevant relationships to disclose. A number of study coauthors disclosed multiple financial relationships.

In patients with intermediate risk of atherosclerotic cardiovascular disease along with risk-enhancing factors, coronary artery calcium scoring may help more precisely calculate their need for statin therapy.

Furthermore, when the need for statin treatment isn’t so clear and patients need additional risk assessment, the scoring can provide further information to personalize clinical decision making, according to a cross-sectional study of 1,688 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) published in JAMA Cardiology.

And regardless of coronary artery calcium (CAC), a low ankle brachial index (ABI) score is a marker for statin therapy, the study found.

The study looked at CAC scoring in the context of ABI and other risk-enhancing factors identified in the 2018 American Heart Association/American College of Cardiology cholesterol management guidelines: a family history of premature atherosclerotic cardiovascular disease (ASCVD), lipid and inflammatory biomarkers, chronic kidney disease, chronic inflammatory conditions, premature menopause or preeclampsia, and South Asian ancestry.

Any number of these factors can indicate the need for statins in people with borderline or intermediate risk. The guidelines also call for selective use of CAC to aid the decision-making process for statin therapy when the risk for developing atherosclerosis isn’t so clear.

“The novel risk-enhancing factors are not perfect,” said lead author Jaideep Patel, MD, director of preventive cardiology at Johns Hopkins Heart Center at Greater Baltimore Medical Center. He noted that the 2018 dyslipidemia guidelines suggested the risk for cardiovascular events rises when new risk-enhancing factors emerge, and that it was difficult to predict the extent to which each enhancer could change the 10-year risk. 
 

Utility of CAC

“In this setting, the most significant finding that supports the utility of CAC scoring is when CAC is absent – a CAC of 0 – even in the setting of any of these enhancers, whether it be single or multiple, the 10-year risk remains extremely low – at the very least below the accepted threshold to initiate statin therapy,” Dr. Patel said.

That threshold is below the 7.5% 10-year ASCVD incidence rate. Over the 12-year mean study follow-up, the ASCVD incidence rate among patients with a CAC score of 0 for all risk-enhancing factors was 7.5 events per 1,000 person years, with one exception: ABI had an incidence rate of 10.4 events per 1,000 person years. “A low ABI score should trigger statin initiation irrespective of CAC score,” Dr. Patel said.

The study found a CAC score of 0 in 45.7% of those with one or two risk-enhancing factors versus 40.3% in those with three or more. “Across all the risk enhancers (except low ABI), the prevalence of CAC of 0 was greater than 50% in women; that is, enhancers overestimate risk,” Dr. Patel said. “The prevalence of CAC of 0 was approximately 40% across all risk enhancers; that is, enhancers overestimate risk.”

Dr. Patel said previous studies have suggested the risk of a major cardiovascular event was almost identical for statin and nonstatin users with a CAC score of 0. “If there is uncertainty about statin use after the physician-patient risk discussion,” he said, “CAC scoring may be helpful to guide the use of statin therapy.”

Senior author Mahmoud Al Rifai, MD, MPH, added: “For example, if CAC was absent, a statin could be deprescribed if there’s disutility on the part of the patient, with ongoing lifestyle and risk factor modification efforts.” Dr. Al Rifai is a cardiology fellow at Baylor College of Medicine, Houston.

Dr. Patel said: “Alternatively, if CAC was present, then it would be prudent to continue statin therapy.”

While South Asian ethnicity is a risk enhancing factor, the investigators acknowledged that MESA didn’t recruit this population group.
 

Study confirms guidelines

The study “supports the contention of the [AHA/ACC] guidelines that, in people who are in this intermediate risk range, there may be factors that either favor statin treatment or suggest that statin treatment could be deferred,” said Neil J. Stone, MD, of Northwestern University, Chicago, and author of the 2013 ASCVD risk calculator. “The guidelines pointed out that risk-enhancing factors may be associated with an increase in lifetime risk, not necessarily short term, and so could inform a more personalized risk discussion.”

The study findings validate the utility of CAC for guiding statin therapy, Dr. Stone said. “For those who have felt that a calcium score is not useful,” he said, “this is additional evidence to show that, in the context of making a decision in those at intermediate risk as proposed by the guidelines, a calcium score is indeed very useful.”

Dr. Stone added: “An important clinical point not mentioned by the authors is that, when the patient has a CAC score of 0 and risk factors, this may be exactly the time to be aggressive with lifestyle to prevent them from developing a positive CAC score and atherosclerosis, because once atherosclerosis is present, treatment may not restore the risk back to the original lower state.”

Dr. Patel, Dr. Al Rifai, and Dr. Stone have no relevant relationships to disclose. A number of study coauthors disclosed multiple financial relationships.

Bicycle riding may help people with diabetes live longer, new research suggests.

NicolasMcComber/E+/Getty Images

Among more than 7,000 adults with diabetes in 10 Western European countries followed for about 15 years, those who cycled regularly were significantly less likely to die of any cause or of cardiovascular causes, even after accounting for differences in factors such as sex, age, educational level, diet, comorbidities, and other physical activities.

“The association between cycling and all-cause and CVD [cardiovascular disease] mortality in this study of person[s] with diabetes was of the same magnitude and direction as observed in the healthy population,” wrote Mathias Ried-Larsen, PhD, of the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and colleagues. The findings were published online July 19, 2021, in JAMA Internal Medicine.

In an accompanying Editor’s Note, JAMA Internal Medicine editor Rita F. Redberg, MD, and two deputy editors said that the new data add to previous studies showing benefits of cycling, compared with other physical activities. “The analysis from Ried-Larsen and colleagues strengthens the epidemiologic data on cycling and strongly suggests that it may contribute directly to longer and healthier lives,” they wrote.

Dr. Redberg, of the University of California, San Francisco, told this news organization: “I think the number of cyclists grew greatly during pandemic, when there was little auto traffic, and people did not want to take public transportation. Cities that add bike lanes, especially protected bike lanes, see an increase in cyclists. I think Americans can cycle more, would enjoy cycling more, and would live longer [by] cycling, to work and for pleasure.”

Dr. Redberg disclosed that she is “an avid cyclist and am currently on a bike ride in Glacier National Park. ... This group [Climate Ride] raises money for more bike lanes, promotes climate change awareness, has paid for solar panels at Glacier, and more.”

However, Dr. Redberg and colleagues also “recognize that cycling requires fitness, a good sense of balance, and the means to purchase a bicycle. We also understand that regular cycling requires living in an area where it is reasonably safe, and we celebrate the installation of more bike lanes, particularly protected lanes, in many cities around the world.”

But, despite the limitations of an observational study and possible selection bias of people who are able to cycle, “it is important to share this evidence for the potentially large health benefits of cycling, which almost surely generalize to persons without diabetes.”
 

Cycling tied to lower all-cause and CVD mortality

The prospective cohort study included 7,459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition. All were assessed during 1992-1998 and again in 1996-2011, with a mean follow-up of roughly 15 years. During that time, there were 1,673 deaths from all causes, with 811 attributed to CVD.

Compared with no cycling, those who reported any cycling had a 24% lower risk of death from any cause over a 5-year period, after adjustment for confounders and for other physical activity. The greatest risk reduction was seen in those who reported cycling between 150-299 minutes per week, particularly in CVD mortality.

In a subanalysis of 5,423 individuals with 10.7 years of follow-up, there were 975 all-cause deaths and 429 from CVD. Individuals who began or continued cycling during follow-up experienced reductions of about 35% for both all-cause and CVD mortality, compared with those who never cycled.

Dr. Redberg and colleagues added that “there are environmental benefits to increasing the use of cycling for commuting and other transport because cycling helps to decrease the adverse environmental and health effects of automobile exhaust.”

They concluded: “As avid and/or aspiring cyclists ourselves, we are sold on the mental and physical benefits of getting to work and seeing the world on two wheels, self-propelled, and think it is well worth a try.”

The study work was supported by the Health Research Fund of Instituto de Salud Carlos III; the Spanish regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra; and the Catalan Institute of Oncology. The Centre for Physical Activity Research is supported by a grant from TrygFonden. Dr. Ried-Larsen reported personal fees from Novo Nordisk. Dr. Redberg reported receiving grants from Arnold Ventures; the Greenwall Foundation; and the National Heart, Lung, and Blood Institute.

Bicycle riding may help people with diabetes live longer, new research suggests.

NicolasMcComber/E+/Getty Images

Among more than 7,000 adults with diabetes in 10 Western European countries followed for about 15 years, those who cycled regularly were significantly less likely to die of any cause or of cardiovascular causes, even after accounting for differences in factors such as sex, age, educational level, diet, comorbidities, and other physical activities.

“The association between cycling and all-cause and CVD [cardiovascular disease] mortality in this study of person[s] with diabetes was of the same magnitude and direction as observed in the healthy population,” wrote Mathias Ried-Larsen, PhD, of the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and colleagues. The findings were published online July 19, 2021, in JAMA Internal Medicine.

In an accompanying Editor’s Note, JAMA Internal Medicine editor Rita F. Redberg, MD, and two deputy editors said that the new data add to previous studies showing benefits of cycling, compared with other physical activities. “The analysis from Ried-Larsen and colleagues strengthens the epidemiologic data on cycling and strongly suggests that it may contribute directly to longer and healthier lives,” they wrote.

Dr. Redberg, of the University of California, San Francisco, told this news organization: “I think the number of cyclists grew greatly during pandemic, when there was little auto traffic, and people did not want to take public transportation. Cities that add bike lanes, especially protected bike lanes, see an increase in cyclists. I think Americans can cycle more, would enjoy cycling more, and would live longer [by] cycling, to work and for pleasure.”

Dr. Redberg disclosed that she is “an avid cyclist and am currently on a bike ride in Glacier National Park. ... This group [Climate Ride] raises money for more bike lanes, promotes climate change awareness, has paid for solar panels at Glacier, and more.”

However, Dr. Redberg and colleagues also “recognize that cycling requires fitness, a good sense of balance, and the means to purchase a bicycle. We also understand that regular cycling requires living in an area where it is reasonably safe, and we celebrate the installation of more bike lanes, particularly protected lanes, in many cities around the world.”

But, despite the limitations of an observational study and possible selection bias of people who are able to cycle, “it is important to share this evidence for the potentially large health benefits of cycling, which almost surely generalize to persons without diabetes.”
 

Cycling tied to lower all-cause and CVD mortality

The prospective cohort study included 7,459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition. All were assessed during 1992-1998 and again in 1996-2011, with a mean follow-up of roughly 15 years. During that time, there were 1,673 deaths from all causes, with 811 attributed to CVD.

Compared with no cycling, those who reported any cycling had a 24% lower risk of death from any cause over a 5-year period, after adjustment for confounders and for other physical activity. The greatest risk reduction was seen in those who reported cycling between 150-299 minutes per week, particularly in CVD mortality.

In a subanalysis of 5,423 individuals with 10.7 years of follow-up, there were 975 all-cause deaths and 429 from CVD. Individuals who began or continued cycling during follow-up experienced reductions of about 35% for both all-cause and CVD mortality, compared with those who never cycled.

Dr. Redberg and colleagues added that “there are environmental benefits to increasing the use of cycling for commuting and other transport because cycling helps to decrease the adverse environmental and health effects of automobile exhaust.”

They concluded: “As avid and/or aspiring cyclists ourselves, we are sold on the mental and physical benefits of getting to work and seeing the world on two wheels, self-propelled, and think it is well worth a try.”

The study work was supported by the Health Research Fund of Instituto de Salud Carlos III; the Spanish regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra; and the Catalan Institute of Oncology. The Centre for Physical Activity Research is supported by a grant from TrygFonden. Dr. Ried-Larsen reported personal fees from Novo Nordisk. Dr. Redberg reported receiving grants from Arnold Ventures; the Greenwall Foundation; and the National Heart, Lung, and Blood Institute.

Bicycle riding may help people with diabetes live longer, new research suggests.

NicolasMcComber/E+/Getty Images

Among more than 7,000 adults with diabetes in 10 Western European countries followed for about 15 years, those who cycled regularly were significantly less likely to die of any cause or of cardiovascular causes, even after accounting for differences in factors such as sex, age, educational level, diet, comorbidities, and other physical activities.

“The association between cycling and all-cause and CVD [cardiovascular disease] mortality in this study of person[s] with diabetes was of the same magnitude and direction as observed in the healthy population,” wrote Mathias Ried-Larsen, PhD, of the Centre for Physical Activity Research, Rigshospitalet, Copenhagen, and colleagues. The findings were published online July 19, 2021, in JAMA Internal Medicine.

In an accompanying Editor’s Note, JAMA Internal Medicine editor Rita F. Redberg, MD, and two deputy editors said that the new data add to previous studies showing benefits of cycling, compared with other physical activities. “The analysis from Ried-Larsen and colleagues strengthens the epidemiologic data on cycling and strongly suggests that it may contribute directly to longer and healthier lives,” they wrote.

Dr. Redberg, of the University of California, San Francisco, told this news organization: “I think the number of cyclists grew greatly during pandemic, when there was little auto traffic, and people did not want to take public transportation. Cities that add bike lanes, especially protected bike lanes, see an increase in cyclists. I think Americans can cycle more, would enjoy cycling more, and would live longer [by] cycling, to work and for pleasure.”

Dr. Redberg disclosed that she is “an avid cyclist and am currently on a bike ride in Glacier National Park. ... This group [Climate Ride] raises money for more bike lanes, promotes climate change awareness, has paid for solar panels at Glacier, and more.”

However, Dr. Redberg and colleagues also “recognize that cycling requires fitness, a good sense of balance, and the means to purchase a bicycle. We also understand that regular cycling requires living in an area where it is reasonably safe, and we celebrate the installation of more bike lanes, particularly protected lanes, in many cities around the world.”

But, despite the limitations of an observational study and possible selection bias of people who are able to cycle, “it is important to share this evidence for the potentially large health benefits of cycling, which almost surely generalize to persons without diabetes.”
 

Cycling tied to lower all-cause and CVD mortality

The prospective cohort study included 7,459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition. All were assessed during 1992-1998 and again in 1996-2011, with a mean follow-up of roughly 15 years. During that time, there were 1,673 deaths from all causes, with 811 attributed to CVD.

Compared with no cycling, those who reported any cycling had a 24% lower risk of death from any cause over a 5-year period, after adjustment for confounders and for other physical activity. The greatest risk reduction was seen in those who reported cycling between 150-299 minutes per week, particularly in CVD mortality.

In a subanalysis of 5,423 individuals with 10.7 years of follow-up, there were 975 all-cause deaths and 429 from CVD. Individuals who began or continued cycling during follow-up experienced reductions of about 35% for both all-cause and CVD mortality, compared with those who never cycled.

Dr. Redberg and colleagues added that “there are environmental benefits to increasing the use of cycling for commuting and other transport because cycling helps to decrease the adverse environmental and health effects of automobile exhaust.”

They concluded: “As avid and/or aspiring cyclists ourselves, we are sold on the mental and physical benefits of getting to work and seeing the world on two wheels, self-propelled, and think it is well worth a try.”

The study work was supported by the Health Research Fund of Instituto de Salud Carlos III; the Spanish regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra; and the Catalan Institute of Oncology. The Centre for Physical Activity Research is supported by a grant from TrygFonden. Dr. Ried-Larsen reported personal fees from Novo Nordisk. Dr. Redberg reported receiving grants from Arnold Ventures; the Greenwall Foundation; and the National Heart, Lung, and Blood Institute.

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Statins are associated with a low risk of adverse events in patients without a history of heart disease, but the potential harms are small and should not deter their use in primary prevention, a new systematic review and meta-analysis concludes.

RogerAshford/Thinkstock

As reported July 14 in BMJ, the analysis showed a slightly increased risk for self-reported muscle symptoms after treatment with statins but no increased risk for clinically confirmed muscle disorders. Statins were associated with liver dysfunction, renal insufficiency, and eye conditions, but not with diabetes.

“These risks are very, very small and, in fact, the adverse events we’re talking about are potentially quite mild, so if you weigh them against the benefits in terms of reduction in major cardiovascular events, the benefit-to-harm ratio is very much in favor of prescribing treatment for almost all patients,” senior author James P. Sheppard, MD, University of Oxford (England), said in an interview.

Although there’s an abundance of data showing that statins prevent recurrent cardiovascular events, their use is controversial in primary prevention, owing partly to the lower risk for cardiovascular disease (CVD). The absolute benefits of statins are smaller in primary prevention than in those with existing CVD, and the benefit-to-harm balance of treatment might be less favorable, the authors note.

A 2019 review suggested that the use of statins in primary prevention may be an example of “low-value care, having little benefit and potential to cause harm,” and a meta-analysis with more than 94,000 trial participants showed statins significantly increased risks for myopathy, renal dysfunction, and hepatic dysfunction.

Nevertheless, clinical guidelines have recommended wider use of statins for primary prevention, calling on physicians to weigh the benefits and harms.

“This is a reasonable expectation but, at present, the data on the harms of treatment are much less well understood in comparison to the benefits and there’s quite a lot of debate about the extent to which statins are associated with adverse events,” Dr. Sheppard said. “So we wanted to look at this in a bit more detail.”

The investigators analyzed results from 62 randomized controlled trials with 120,456 participants (mean age, 61; 40% women) followed for a mean of 3.9 years. All but two studies enrolled participants with hyperlipidemia or dyslipidemia. Common comorbidities were diabetes (11 studies), asymptomatic atherosclerosis (nine studies), and hypertension (four studies).

Statins increased risks for self-reported muscle symptoms in 21 trials (odds ratio [OR], 1.06), liver dysfunction in 21 trials (OR, 1.33), renal insufficiency in eight trials (OR, 1.14), and cataracts or other eye-related conditions in six trials (OR, 1.23).

At the same time, statins decreased risks for myocardial infarction in 22 trials (OR, 0.72), stroke in 17 trials (OR, 0.80), and CVD death in 22 trials (OR, 0.83).

These risks translated into 15 more events of muscle symptoms, 8 more liver events, 12 more kidney events, and 14 more eye conditions per 10,000 patients treated for a year.

Statins were estimated to prevent 19 myocardial infarctions, 9 strokes, and 8 CVD deaths per 10,000 patients treated for a year.

Dr. Sheppard suggested that the inclusion of previously omitted trials and the decision to classify muscle problems as self-reported symptoms or clinically defined muscle disorders based on changes in creatine kinase might explain why they found the association with statins, whereas most systematic reviews have not.

“Some people would argue that these side effects are so small and so negligible that we shouldn’t talk about them, but the problem with doing that is if you’ve got a patient who has a preconceived idea that statins are harmful,” he added. “So having some empirical data where you can actually say: ‘Look, just 15 people out of 10,000 patients who’ve been treated for a year might experience one of those self-reported muscle symptoms,’ hopefully, will be helpful for physicians having discussions in practice.”

The analysis is “another data point indicating the overall safety and net benefit of statins for patients, even in primary prevention,” Donald M. Lloyd-Jones, MD, ScM, chair of preventive medicine, Northwestern University, Chicago, said in an interview.

He noted that the renal insufficiency findings are difficult to interpret, given that the endpoint was defined as “any decline in renal function,” but that most will have been clinically unimportant. In general, most studies didn’t systematically look to ascertain some of adverse events but relied on participant or physician report. “Nonetheless, there is little reason to suspect bias in the collection of these data among the blinded studies.

“Although not definitive, given the study design and inclusion of very different types of studies and variable ascertainment of adverse events, the findings are reassuring that the risks of adverse events were small, and the potential adverse events identified were not very clinically significant and clearly outweighed by the important beneficial reductions in major cardiovascular events,” said Dr. Lloyd-Jones.

“This study is yet another reminder of the safety of statins,” Ann Marie Navar, MD, PhD, a specialist in preventive cardiology at UT Southwestern Medical School, Dallas, said in an email.

“I’m pleased to have a comprehensive study like this – a well-done, systematic review of randomized trials – to help combat the vast amounts of misinformation about statins circulating on the Internet.”

Dr. Lloyd-Jones also acknowledged the need to address misinformation, pointing out that the loss of contact with physicians and the adverse effects of the pandemic on weight and other health behaviors mean that many patients have had worsening of their cardiovascular risk factors.

“We must continue to help patients and the public understand that statins are beneficial for patients at sufficient risk for cardiovascular disease because of elevated cholesterol or their total burden of risk factors,” Dr. Lloyd-Jones said. “We must also be upfront about the risks of potential side effects, which are uncommon and almost always very easily managed with washout and dose reduction or switching to a different drug in the same class.”

Analyses by type of statin, however, showed few significant differences in adverse events. Rosuvastatin was associated with increased risks for self-reported muscle symptoms, renal insufficiency, diabetes, and eye conditions, whereas atorvastatin and lovastatin increased the risk for liver dysfunction.

In dose-response meta-analyses, a possible modest dose-response relationship was detected only for the effect of atorvastatin on liver dysfunction.

The current data do not support tailoring the type of statin or dosage to reduce adverse events, the authors say, although routine monitoring of liver function during treatment is probably warranted in primary prevention, given the increased risk for liver dysfunction.

To help improve adherence to statins, the investigators said, additional studies are needed to identify patient characteristics crucial to the small risks of adverse events.

Limitations of the research, they said, are that many of the analyses were underpowered to detect between-group differences, many trials had short periods of follow-up, and some trials excluded vulnerable people more likely to have adverse events, such as those with high serum creatinine.

The study was funded by a British Heart Foundation PhD Scholarship held by first author Ting Cai. Dr. Sheppard reports receiving funding from a Wellcome Trust/Royal Society Sir Henry Dale Fellowship. Disclosures for other authors are listed in the paper. Dr. Lloyd-Jones and Dr. Navar report having no conflicts of interest.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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

Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.

The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.

In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.

The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.

“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.

He presented the new data at the 2021 annual congress of the European Association of Urology.

Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”

Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.

“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
 

Registry study

The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.

At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.

The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.

The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).

All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.

Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”

No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.

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