Journal of the American College of Cardiology · Nov 2026
Evolocumab in Patients with Reduced Kidney Function Without a Prior MI or Stroke in VESALIUS-CV
By Cornel JH, Giugliano RP, Bhatia A et al.
Background Patients with reduced kidney function are at high risk for major adverse cardiovascular events and are frequently undertreated for hyperlipidemia. Objectives This pre-specified analysis of VESALIUS-CV evaluated the efficacy and safety of the PCSK9i evolocumab for preventing first CV events in patients with reduced kidney function. Methods VESALIUS-CV randomized 12,257 patients with qualifying atherosclerosis or high-risk diabetes, without prior MI or stroke, and LDL-C ≥ 90mg/dL to evolocumab or placebo. The dual primary endpoints were a composite of coronary heart disease death, MI or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Efficacy was assessed in the subgroup with reduced estimated glomerular filtration rate (eGFR) at baseline, defined as 15 to < 60 ml/min/1.73m². Results In 2,140 patients (17.5%) with reduced eGFR, the median eGFR was 51 [Q1-Q3, 44-56] ml/min/1.73m², median age 69 years [64-73], and 55% were female. In patients with reduced eGFR in the lipid substudy, the median LDL-C at 48 weeks was 111 mg/dL in the placebo group versus 44 mg/dL in the evolocumab group (p<0.0001). Patients with eGFR<60 in the placebo group had ∼2-fold the rate of 3-P MACE compared with patients an eGFR≥60 (HR 1.90; 95% CI 1.55-2.34). After 4.6 years median follow-up, evolocumab decreased 3-P MACE rates by 39% (HR 0.61; 95% CI 0.46-0.81, P=0.0007) and 4-P MACE rates by 23% (HR 0.77; 95% CI 0.63-0.95, P=0.015), with absolute risk reductions (ARR) at 5 years of 4.0% and 4.1%, respectively, in patients with reduced eGFR. The corresponding relative and absolute risk reductions were 20% and 18% and 1.3% and 2.4% in those without reduced eGFR. The 5-year Kaplan-Meier rates of all-cause death in patients with reduced eGFR were 12.0% vs. 16.7% (ARR 4.7%) in the evolocumab versus placebo arms (HR 0.71; 95% CI 0.56-0.90) and 7.0% vs 8.1% (ARR 1.1%) in those without reduced eGFR (HR 0.84; 95% CI 0.72-0.98). Conclusions Intensive LDL-C lowering to a median of 44 mg/dL with evolocumab reduced the risk of first CV events in patients with reduced eGFR without a prior MI or stroke, with consistent relative and numerically greater absolute benefits. Clinical Trial Registration NCT03872401