In a subgroup analysis of VESALIUS-CV, 3,655 patients with diabetes but no known significant atherosclerosis were followed for a median of 4.8 years. Evolocumab reduced 3-P MACE by 31% (HR 0.69; P=0.009) and 4-P MACE by 31% (HR 0.69; P=0.001). The effect appeared after 1 year and grew to ~40% reduction thereafter. CV death was reduced by 32% and all-cause mortality by 24%. This supports the use of PCSK9 inhibitors for primary prevention in high-risk diabetes patients.
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.
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).
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).
In patients without significant atherosclerosis, evolocumab substantially reduced the risk of a first major CV event.
