Lower-intensity statins plus bile acid sequestrant considered good option for some heart patients, study finds

Combination therapy with a lower-intensity statin and bile acid sequestrant or ezetimibe lowered LDL cholesterol similar to or better than higher-intensity statin monotherapy among patients with high risk for atherosclerotic cardiovascular disease (ASCVD), according to a study published February 11 online in the Annals of Internal Medicine.

However, the researchers at Johns Hopkins were unable to determine whether these regimens led to decreased ASCVD risk. “Rates of side effects were similar between these groups when reported,” said study author Kimberly Gudzune, MD, MPH, an assistant professor of medicine in the Division of General Internal Medicine at Johns Hopkins University School of Medicine. “We found insufficient evidence to support combination therapy with lower-intensity statin and fibrates, niacin, or omega-3 fatty acids.”

Researchers conducted a systematic review, where they consolidated information from clinical trials that examined combination regimens with lower-intensity statin and another FDA-approved agent for lipid modification to higher-intensity statin monotherapy in adults at high risk for heart disease.

“We aimed to determine which combination regimens may be the best options to consider for patients with respect to lowering cardiovascular disease risk, LDL cholesterol, and side effects,” Dr Gudzune said. “No prior study had synthesized the scientific evidence in order to weigh the benefits and risks of this proposed strategy.”

Late last year, the American College of Cardiology and the American Heart Association issued new guidelines on lipid management, which shifted clinical practice away from focusing on LDL cholesterol targets to instead using moderate- or high-intensity statin monotherapy regardless of LDL cholesterol level as a way to reduce ASCVD among higher-risk patients.

“While evidence supports this strategy, we believe that these guidelines present a challenge for clinicians who have patients that cannot tolerate higher-intensity statins due to side effects or patients who do not respond to statin therapy,” said Anne Monroe, MD, MSPH, assistant professor of medicine, Johns Hopkins University School of Medicine.

The new guidelines state that clinicians can consider combination therapy with a lower-intensity statin and another lipid-modifying regimen among high-risk patients in these scenarios; however, they do not offer recommendations on which regimens to consider. 

“We were prompted to conduct this study to try to provide guidance on this question,” Dr Monroe said.

“We believe that our results can provide information to managed care and hospital decision-makers in certain areas,” said Dr Monroe. “Individuals may want to consider our results when developing pharmaceutical formularies, where it may be prudent to provide coverage for combination therapy regimens that have greater demonstrated LDL cholesterol-lowering benefits.

“In addition, individuals involved in the development of clinical-decision support tools may want to integrate these results into their system to help clinicians implement an evidence-based strategy in selecting a combination therapy regimen among high-risk statin-intolerant or statin-unresponsive patients. Such tools should also highlight that we do not know whether these regimens reduce atherosclerotic cardiovascular disease risk,” Dr. Monroe concluded.

High-intensity statin monotherapy has demonstrated benefits with regard to lowering ASCVD, so this strategy should always be considered first, according to the researchers.

“However, for statin-intolerant or statin-unresponsive patients, clinicians can use our results to facilitate evidence-based discussions when considering a combination regimen,” said Dr Gudzune. 

Currently, there are 5 categories of non-statin medications approved to manage lipids: Bile acid sequestrant, ezetimibe, fibrates, niacin, and omega-3 fatty acids.

“Understanding the evidence on benefits and risks of each approach is important when selecting a strategy,” Dr. Gudzune said. “Using our results, clinicians can discuss the potential LDL cholesterol-lowering benefits of combination therapy with lower-intensity statin and bile acid sequestrant or ezetimibe, yet they should caution patients that we do not know whether these regimens will decrease their atherosclerotic cardiovascular risk. Such conversations are also an opportunity to talk about side effects of each regimen. Ultimately, we hope that our results will help patients and clinicians make an informed decision together.”