Evolocumab can help attenuate the elevated risk of major adverse cardiovascular events (MACE) that individuals with obesity and atherosclerotic cardiovascular disease (ASCVD) face, according to a prespecified analysis from the FOURIER trial published Dec. 10 in JACC.

The double-blind trial randomized 27,564 patients with stable ASCVD to either placebo or subcutaneous evolocumab (either 140 mg every 2 weeks or 420 mg once monthly) for a median follow-up period of 2.2 years.

Among participants, 16,558 were classified as not obese with a BMI <30 kg/m²; 7,496 had class 1 obesity (BMI ≥30 to <35 kg/m²); and 3,446 had class 2-3 obesity (≥35 kg/m²). Those with higher levels of obesity were slightly younger and more likely to be women.

Results in the placebo arm showed that every five-unit higher BMI carried an 11% higher risk of the primary endpoint of cardiovascular death, MI, stroke, hospitalization for unstable angina or coronary revascularization.

However, within the treatment arm, evolocumab reduced risk at a progressively greater rate in those with higher BMI (≥30 kg/m²), modeled on a continuous basis (pint=0.025). In those with no obesity, evolocumab reduced risk of primary endpoint by 11% with a corresponding absolute risk reduction of 1.4%. In those with class 1 obesity, treatment reduced risk by 14% with an absolute risk reduction of 1.8%, and in those with class 2-3, risk was reduced by 29% with an absolute risk reduction of 5.7%.

"[Cardiovascular] disease remains the leading cause of obesity-related death in patients with or without known ASCVD," write study authors Yu Mi Kang, MD, PhD, MPH, et al. "The current analysis highlights the excess in [cardiovascular] risk that may exist for those with class 2 or 3 obesity and the relatively greater benefit derived for those individuals with more intensive LDL-C lowering with evolocumab."