Evolocumab also effective in ASCVD patients with obesity

ESC 2024 – In a FOURIER substudy among high-risk patients with ASCVD, the reduction of MACE risk with evolocumab versus placebo appeared to be greater in those with obesity (particularly BMI ≥35 kg/m²).

This summary is based on the presentation of Yu Mi Kang, MD, PhD (Boston, MA, USA) at the ESC Congress 2024 - Cardiovascular Efficacy of Evolocumab in Patients with Obesity: Updates from FOURIER Trial.

Introduction and methods

Previously, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial showed evolocumab reduced LDL-c levels and risk of MACE compared with placebo in high-risk patients with established ASCVD. However, the efficacy of PCSK9 inhibitors in patients across the range of BMI remains unclear. In a subgroup analysis of the FOURIER trial, the efficacy of evolocumab was assessed by baseline BMI.

The FOURIER trial was an international, multicenter, double-blind, placebo-controlled, phase 3 RCT, among 27,564 patients with stable ASCVD (prior MI, prior stroke, or symptomatic peripheral artery disease) and LDL-c ≥70 mg/dL (≥1.8 mmol/L) or non–HDL-c ≥100 mg/dL (≥2.6 mmol/L) despite high- or moderate-intensity statin therapy. Participants were randomized to subcutaneous evolocumab (140 mg every 2 weeks or 420 mg every 4 weeks) or matching placebo. Median follow-up duration was 2.2 years. At baseline, 5012 patients (18%) had BMI <25 kg/m² and 3446 (13%) had BMI ≥35 kg/m².

The primary efficacy endpoint was MACE, defined as a composite outcome of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy endpoint was a composite outcome of CV death, MI, or stroke.

Main results

• In the placebo arm of the study, the risk of primary efficacy endpoint of MACE at 3 years increased with increasing BMI. For example, there was a risk increase of 8% for every 5-unit increase of the BMI in patients with BMI >25 kg/m² (adjusted HR: 1.08; 95%CI: 1.02–1.15).
• Among patients treated with evolocumab, the placebo-corrected least-squares mean percentage change in LDL-c level was similar in patients with baseline BMI ≥35 kg/m² (–53%) and those with BMI <35 kg/m² (–60%).
• When baseline BMI was analyzed as a continuous variable, the treatment effect of evolocumab over placebo on the risk of the primary efficacy endpoint at 3 years appeared to be greatest in patients with BMI >30 kg/m² (P for interaction per 5-unit BMI increase=0.025).
• Across 3 BMI categories (<30.0; 30.0–34.9; and ≥35.0 kg/m²), the risk reduction in the primary efficacy endpoint at 3 years with evolocumab versus placebo was greatest in patients with the highest BMI (HR: 0.71; 95%CI: 0.59–0.86; absolute risk reduction: 5.7%; number need to treat: 18).
• Similar results were seen for the key secondary efficacy endpoint.

Conclusion

In this FOURIER subgroup analysis among high-risk patients with ASCVD, the clinical efficacy of evolocumab versus placebo appeared to be greater in those with obesity (particularly BMI ≥35 kg/m²). Dr. Kang concluded that “intensive LDL-c control should be strongly considered in individuals with obesity to help mitigate their high CVD risk.”

- Our reporting is based on the information provided at the ESC Congress 2024 -