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Amgen: Repatha linked to 20% fewer heart attacks than ezetimibe in analysis of 544,103 patients

In a non-randomized analysis of US database records, adults with ASCVD and prior statin therapy had a 20% lower heart attack rate on evolocumab than on ezetimibe.

Amgen: Repatha linked to 20% fewer heart attacks than ezetimibe in analysis of 544,103 patients
Photo: ad-hoc-news.de

Amgen researchers report that in adults with atherosclerotic cardiovascular disease (ASCVD) and prior statin therapy, the PCSK9 inhibitor evolocumab (Repatha) was associated with fewer heart attacks than ezetimibe. The study was published in November 2026 in The American Journal of Preventive Cardiology, as described by ad-hoc-news.de. ad-hoc-news.dead-hoc-news.dead-hoc-news.deOpen source ↗ Over follow-up of up to four years, the rate of fatal and non-fatal heart attacks was 20% lower with evolocumab (hazard ratio 0.80; 95% CI 0.70–0.91).

The cohort was drawn from the Komodo Healthcare Map database and included 544,103 US adults: 64,421 new evolocumab users and 479,682 new ezetimibe users. Patients were enrolled from January 2017 to December 2024, and follow-up ran to June 2026.

Heart attack risk by subgroup

Among 225,048 patients with a documented baseline LDL cholesterol, the cumulative four-year heart attack risk was 5.88% (95% CI 4.77–7.00) with Repatha and 7.76% (95% CI 7.31–8.20) with ezetimibe. That is a difference of about 1.9 percentage points. In the 319,055 patients without a documented baseline value, the four-year risk was 5.65% with Repatha and 7.06% with ezetimibe.

The effect was larger in patients taking statins at baseline. In this subgroup the risk was 37% lower with evolocumab (HR 0.63; 95% CI 0.54–0.75). ad-hoc-news.dead-hoc-news.dead-hoc-news.deOpen source ↗ Paul Burton, Amgen's chief medical officer, said the direct comparison showed a significant benefit for fatal and non-fatal heart attacks.

Design and limitations

No randomized head-to-head trials of the two drugs exist, so the analysis used target trial emulation with statistical weighting. Median baseline LDL-C was higher in the evolocumab group (114 mg/dL) than in the ezetimibe group (99 mg/dL), and a baseline value was available for only 41.4% of participants. Median follow-up was 4.3 months on Repatha and 5.8 months on ezetimibe.

Earlier randomized trials tested each drug class against other comparators. IMPROVE-IT examined ezetimibe added to simvastatin after acute coronary syndrome. FOURIER, with 27,564 patients, showed 27% fewer heart attacks with evolocumab plus a statin than with placebo. VESALIUS-CV recorded a 36% reduction in higher-risk patients with no prior heart attack or stroke.

In August 2025 the US FDA extended Repatha's approval to adults at elevated risk of major cardiovascular events because of uncontrolled LDL-C. ad-hoc-news.dead-hoc-news.dead-hoc-news.deOpen source ↗

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