Combination statin and ezetimibe could be a life-saver for high-risk patients

Patients at high risk of heart attack and stroke should be treated with a combination of a statin and ezetimibe, and as soon as possible, researchers have concluded after a large meta-analysis of relevant data.

The findings appeared on the March 23, 2025 in Mayo Clinic Proceedings. 

“Combination LLT [lipid-lowering therapy] was associated with an overall greater reduction in LDL-C [low-density lipoprotein cholesterol], the same risk of adverse effects, and significantly lower risk of all-cause mortality, major adverse cardiovascular events, and stroke compared with statin monotherapy,” the authors said.

Data from over 100,000 very high-risk subjects were included in the final analysis.

The goal was to evaluate the efficacy of combination therapy compared with statin monotherapy for low-density lipoprotein cholesterol reduction and for associated adverse events and outcomes.

The investigators conducted a systematic literature review of databases to identify relevant studies published through 2024. They found 14 studies with 108,373 very high-risk patients.

The mean age of the subjects in the combination LLT group and the statin monotherapy group was 67.31 and 67.89 years, respectively.

Analysis of the pooled showed that when ezetimibe was administered with a high dose statin, the subjects on the combination therapy achieved a significant 19% reduction in the risk of death from any cause when compared to subjects treated with high doses of statin monotherapy, and a 16% reduction in risk of death from cardiovascular causes.

They also achieved a reduction in the incidence of major adverse cardiovascular events (18%) and stroke (17%) compared to the monotherapy cohort.

There was no significant difference between treatment groups for adverse events and treatment discontinuation.

Co-author Peter Toth, MD, Ph.D, Professor of Clinical Family and Community Medicine, University of Illinois, and Adjunct Associate Professor of Medicine at Johns Hopkins University, USA, said, “This study confirms that combined cholesterol lowering therapy should be considered immediately and should be the gold standard for treatment of very high-risk patients after an acute cardiovascular event. Simply adding ezetimibe to statin therapy, without waiting for at least two months to see the effects of statin monotherapy, which is suboptimal in many patients, is associated with more effective LDL-C goal achievement and is responsible for significant incremental reductions in cardiovascular health problems and deaths.”

“This approach does not require additional funding or reimbursement of new expensive drugs. In fact, it may translate into lower rates of first and subsequent heart attacks and stroke, and their complications like heart failure, which are extremely costly for all healthcare systems,” Toth added.