VESALIUS-CV: evolocumab verlaagt risico op eerste cardiovasculair event met 31% bij patiënten zonder significant atherosclerose

Background: Intensive LDL-C lowering with PCSK9 inhibitors has largely been reserved for patients with significant atherosclerosis. We investigated whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without significant atherosclerosis. Methods: VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab in 12,257 patients with qualifying atherosclerosis or diabetes, no prior MI or stroke, and LDL-C >=90 mg/dL. In this subgroup analysis, we examined outcomes in patients without known significant atherosclerosis (eg, any arterial stenosis >=50% or CAC >=100). The dual primary endpoints were composites of coronary heart disease death, MI, or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Results: This cohort included 3,655 patients (median age 65 yrs, 57% female) followed for a median of 4.8 yrs. Among those in the lipid substudy, LDL-C at 48 wks was 52 vs. 111 mg/dL in the evolocumab vs. placebo arms (p<0.0001). Evolocumab significantly reduced the risk of 3-P MACE and 4-P MACE each by 31% (HR 0.69 [0.52-0.91], p=0.009; HR 0.69 [0.55-0.86], p=0.001). The effect became apparent after 1 year, with 41% and 39% reductions in the risk of 3-P MACE and 4-P MACE thereafter. The HR for CV death was 0.68 (0.46-0.99) and the HR for all-cause mortality was 0.76 (0.61-0.95). Conclusion: In patients without significant atherosclerosis, evolocumab substantially reduced the risk of a first major CV event.