The cholesterol-lowering drug evolocumab may provide substantial heart-protective benefits in patients with obesity and cardiovascular disease, according to a new study. The study’s findings revealed that for each 5-point increase in BMI above 30, participants were 11% more likely to experience at least one of these major events — death from heart disease, a heart attack, stroke, hospitalization for unstable angina or the need for a coronary procedure. “Evolocumab reduced the risk of the primary endpoint by 11% in those with a BMI <30 kg/m², by 14% in those with BMI of 30 to <35 kg/m², and by 29% in those with BMI ≥35 kg/m²,” wrote the paper’s authors. “The corresponding absolute risk reductions were 1.4%, 1.8%, and 5.7%, respectively.” The analysis, led by Yu Mi Kang, MD, PhD, from the Brigham and Women’s Hospital and Harvard Medical School in Boston, evaluated data from over 27,000 participants in the FOURIER trial. Higher BMI Further findings included the observation that evolocumab’s effect on cholesterol levels was consistent across all weight categories, yet patients with higher BMI saw greater overall benefit. “The clinical benefit of evolocumab appeared to be accentuated in patients with higher baseline BMI despite having similar effects on the extent of LDL-C lowering,” wrote the paper’s authors. The study also highlighted that obesity was associated with chronic inflammation, diabetes and abnormal lipid metabolism, which combined raised cardiovascular risk. By focusing on lowering LDL cholesterol via PCSK9 inhibition, evolocumab may aid in offsetting this metabolic burden. The research team wrote that therapies like evolocumab could function as “complementary pathways” to weight-loss approaches and alternative cardiovascular treatments, particularly for patients who find significant weight loss difficult to achieve or maintain. Closing treatment gaps As obesity rates have more than doubled globally since 1990, the study provides a case for evolocumab’s use in closing the treatment gap for patients with a heightened cardiovascular risk. “Individuals with obesity and atherosclerotic cardiovascular disease face an elevated risk of major adverse cardiovascular events compared with those without obesity, and evolocumab helps to attenuate this risk,” wrote the paper’s authors. These findings underscore that beyond lifestyle and weight-loss efforts, intensive lipid lowering with evolocumab can meaningfully reduce the risk of heart attack, stroke and cardiovascular death in people with obesity. Source: Kang YM, Giugliano RP, Keech AC, et al. Obesity-Associated Cardiovascular Risk and Benefit From PCSK9 Inhibition: A Prespecified Analysis From FOURIER. J Am Coll Cardiol. 2025 Dec 15 (Article in Press). Image Credit: Halfpoint – stock.adobe.com