Study Shows Evolocumab Lowers Heart Attack Risk More Than Ezetimibe

A comprehensive real-world study published in The American Journal of Preventive Cardiology has found that the injectable cholesterol-lowering medication evolocumab, sold by Amgen as Repatha, is associated with a 20% lower risk of fatal or nonfatal myocardial infarction compared to the oral medication ezetimibe. The retrospective analysis evaluated more than 544,000 United States adults diagnosed with atherosclerotic cardiovascular disease who had prior statin use.

The study analyzed de-identified records from the Komodo Healthcare Map database between January 2017 and December 2024, with patient follow-up extending through June 2026. Out of the total cohort, 64,421 patients initiated treatment with evolocumab, while 479,682 patients started ezetimibe. Investigators utilized a target trial emulation framework alongside inverse probability weighting to balance baseline characteristics and account for changes in treatment throughout the observation period.

Among participants with available baseline low-density lipoprotein cholesterol measurements, the estimated cumulative four-year risk of experiencing a heart attack was 5.88% for those taking evolocumab, compared to 7.76% for patients taking ezetimibe. For individuals without baseline measurements, the estimated risks were 5.65% and 7.06% respectively. Overall, the comparative effectiveness analysis yielded a hazard ratio of 0.80.

Paul Burton, chief medical officer at Amgen, emphasized the significance of the findings for physicians navigating lipid-management decisions. "For physicians deciding what treatment to add next, whether that's prescribing patients Repatha or ezetimibe, this large real-world study provides clear evidence to help inform that choice," Burton stated, noting that patients receiving Repatha experienced a significantly reduced risk of fatal or nonfatal cardiac events.

The research addresses a notable gap in clinical guidance. Nihar Desai, associate professor of medicine and vice chief of the Section of Cardiovascular Medicine at Yale University School of Medicine, pointed out that while recent updates from the American College of Cardiology and the American Heart Association recognize both medications as non-statin options for atherosclerotic cardiovascular disease, clinicians previously lacked direct cardiovascular outcomes evidence comparing the two therapies to help patients reach recommended low-density lipoprotein cholesterol goals.

Subgroup analyses further highlighted the impact of combination therapies. Among patients actively receiving statins at the time they initiated a nonstatin treatment, evolocumab was associated with a 37% lower rate of fatal or nonfatal myocardial infarction compared to ezetimibe. Prespecified sensitivity analyses that tracked patients regardless of subsequent changes to background statin therapy produced consistent results.

Despite the extensive scale of the observational research, study authors acknowledged several limitations. Administrative claims data could not entirely capture patient preferences, insurance denials, or underlying reasons for statin intolerance. Furthermore, baseline measurements were only available for roughly 41.4% of participants, necessitating statistical calibration to manage missing data, and actual median follow-up periods were substantially shorter than the four-year projections.

Researchers noted that while the data provides valuable comparative insights for primary care physicians and cardiologists, randomized head-to-head clinical trials would be required to definitively establish whether evolocumab offers superior clinical protection over ezetimibe. Treatment selection should continue to reflect individual patient risk profiles, administration routes, medication costs, and overall preferences.