Key result
Evolocumab cuts 3-P MACE ~39% vs. placebo in patients with reduced eGFR without prior MI/stroke.
Why the study?
The efficacy and safety of the PCSK9i evolocumab for preventing first CV events in patients with reduced kidney function without a prior MI or stroke required evaluation.
Does evolocumab reduce the risk of first cardiovascular events (3-P MACE and 4-P MACE) in patients with reduced kidney function and qualifying atherosclerosis or high-risk diabetes without a prior MI or stroke?
RCT (n=12,257)
Placebo-controlled
Randomized
Does evolocumab reduce the risk of first cardiovascular events (3-P MACE and 4-P MACE) in patients with reduced kidney function and qualifying atherosclerosis or high-risk diabetes without a prior MI or stroke?
Intensive LDL-C lowering with evolocumab to a median of 44 mg/dL significantly reduces first major adverse cardiovascular events and all-cause mortality in high-risk primary prevention patients with chronic kidney disease (eGFR <60 ml/min/1.73m²), yielding numerically greater absolute risk reductions than in those with preserved kidney function.
Answers are grounded in this paper and cite their sources.
Supports further investigation of evolocumab in CKD primary prevention; leaves open clinical adoption pending dedicated trials.
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. 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.
No takes yet. Share an insight, caveat, or question.
Cornel et al. (2026) conducted an RCT in Qualifying atherosclerosis or high-risk diabetes without prior MI or stroke, with focus on the subgroup of 2,140 patients with reduced kidney function (eGFR <60 ml/min/1.73m²) (n=12,257). Evolocumab vs. Placebo was evaluated on 3-P MACE in patients with reduced eGFR (HR 0.61, 95% CI 0.46-0.81, p=0.0007). Evolocumab reduced 3-P MACE by 39% compared with placebo in patients with reduced eGFR without prior MI or stroke (HR 0.61; 95% CI 0.46-0.81; P=0.0007).
Synapse has enriched 10 related papers. Consider them for comparative context: