Evolocumab linked to fewer heart attacks than ezetimibe

Clinical takeaway: Consider these comparative data when selecting additional LDL-lowering therapy for adults with atherosclerotic cardiovascular disease (ASCVD) whose LDL-C remains above goal despite statin therapy. Evolocumab was associated with fewer fatal or nonfatal myocardial infarctions than ezetimibe, although the observational findings cannot establish causation.

Many patients with ASCVD need additional LDL-C lowering treatment beyond statins. Direct comparisons of cardiovascular outcomes with non-statin therapies can help inform the next treatment choice.

The Amgen-sponsored real-world study included 544,103 US adults with ASCVD and prior statin use. Between 2017 and 2024, 64,421 initiated evolocumab and 479,682 initiated ezetimibe. Investigators assessed fatal or nonfatal MI over up to four years, with follow-up through June 2026.

Using deidentified Komodo Healthcare Map data, researchers applied a framework designed to emulate a clinical trial. They statistically balanced measured baseline characteristics and accounted for incomplete baseline LDL-C data.

Evolocumab was associated with a 20% lower rate of fatal or nonfatal MI than ezetimibe. Among 225,048 patients with baseline LDL-C measurements, the estimated four-year MI risk was 5.88% with evolocumab versus 7.76% with ezetimibe.

Among patients without baseline LDL-C measurements, corresponding estimates were 5.65% versus 7.06%. A sensitivity analysis that continued follow-up regardless of changes in background statin therapy produced consistent results.

Despite the statistical adjustments, unmeasured differences between treatment groups could have influenced outcomes. The findings support treatment discussions but do not establish that evolocumab is the preferred option for every patient.

“These findings provide important comparative data that can help clinicians distinguish between these treatment options and make more informed choices to reduce their patients’ cardiovascular risk,” said Yale cardiologist Nihar Desai, MD, MPH, in Amgen’s press release.

Source: Amgen. (2026 Nov 5) Repatha Lowers Risk of Heart Attacks by 20% Compared with Ezetimibe in a Large Real-World Study