Amgen: Repatha lowers heart attack risk 20% vs ezetimibe in large real‑world cohort

Publication and population

Results from a large real‑world study published in The American Journal of Preventive Cardiology compared cardiovascular outcomes in adults with atherosclerotic cardiovascular disease (ASCVD) who initiated evolocumab or ezetimibe in U.S. clinical practice. The analysis identified 544,103 adults in the Komodo Healthcare Map database, including 64,421 evolocumab initiators and 479,682 ezetimibe initiators, with follow‑up through June 2026.

Design and endpoint

The study used a non‑interventional, active‑comparator, new‑user cohort design applying a target‑trial framework. The primary outcome was fatal or nonfatal myocardial infarction (MI) over up to four years of follow‑up. Analyses balanced measured baseline characteristics via inverse‑probability weighting and used a calibrated estimator to address incomplete baseline LDL‑C availability.

Key findings

Treatment with evolocumab was associated with a 20% lower risk of fatal or nonfatal MI versus ezetimibe (HR 0.80; 95% CI 0.70–0.91). In patients with a baseline LDL‑C measurement (N = 225,048), four‑year cumulative MI risks were 5.88% for evolocumab versus 7.76% for ezetimibe; similar absolute differences were observed when baseline LDL‑C was unavailable. Prespecified sensitivity analyses that continued follow‑up regardless of changes in background statin therapy produced consistent results.

Clinical context

The authors note the findings add comparative cardiovascular outcomes evidence to guide non‑statin treatment choices, alongside guideline recognition of both ezetimibe and PCSK9 inhibitors for patients with ASCVD who need further LDL‑C lowering to reach targets such as <70 mg/dL and <55 mg/dL.