Obesity-Associated Cardiovascular Risk and Benefit From PCSK9 Inhibition

BACKGROUND: The PCSK9 inhibitor evolocumab decreases the risk of major adverse cardiovascular events (MACE). The relationship between body mass index (BMI) and benefit of evolocumab remains unknown. OBJECTIVES: This study sought to investigate the association between BMI, risk of MACE, and the clinical benefit of evolocumab. METHODS: The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized 27,564 stable atherosclerotic cardiovascular disease patients to evolocumab or placebo (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The association between BMI and cardiovascular risk was examined in the placebo arm adjusting for clinical predictors. Effect modification by treatment arm was assessed using an interaction term in the Cox model. Kaplan-Meier rates are at 3 years. RESULTS: (HR: 0.71; 95% CI: 0.59-0.86). The corresponding absolute risk reductions were 1.4%, 1.8%, and 5.7%, respectively. CONCLUSIONS: Individuals with obesity and atherosclerotic cardiovascular disease face an elevated risk of MACE compared with those without obesity, and evolocumab helps to attenuate this risk.