Evolocumab Lowers First Event Risk in Diabetes Primary Prevention

In VESALIUS-CV, investigators reported lower first major cardiovascular event rates with evolocumab than with placebo in a prespecified diabetes subgroup without known significant atherosclerosis. The trial was randomized, double-blind, and placebo-controlled, with both groups treated on top of optimally tolerated statin therapy. Across the parent study, 12,257 patients were enrolled at 774 sites in 33 countries. This subgroup analysis focused on primary prevention in patients with diabetes and no known significant atherosclerosis.

Investigators defined the subgroup as patients with diabetes and no known significant atherosclerosis: no prior arterial revascularization, no arterial stenosis ≥50%, and no coronary artery calcium score ≥100 Agatston units. The prespecified subgroup included 3,655 participants, representing a source-defined diabetes cohort without overt atherosclerotic disease.

In the lipid substudy at 48 weeks, the authors reported median LDL-C of 52 mg/dL with evolocumab and 111 mg/dL with placebo. The results describe substantial separation between treatment groups within the substudy population.

For the 3-point composite (3-P MACE: coronary heart disease death, myocardial infarction, or ischemic stroke), events occurred in 83 evolocumab-treated patients and 117 placebo-treated patients; 5-year Kaplan-Meier estimates were 5.0% and 7.1%, respectively, with a hazard ratio of 0.69. For the broader 4-point composite, events occurred in 127 patients receiving evolocumab and 178 receiving placebo, with 5-year estimates of 7.6% and 10.5% and the same hazard ratio. In this subgroup, both prespecified major cardiovascular composites were lower with evolocumab than with placebo.

All-cause deaths were reported in 136 patients assigned to evolocumab and 172 assigned to placebo, corresponding to 5-year Kaplan-Meier estimates of 7.8% and 10.1% and a hazard ratio of 0.76. The authors concluded that evolocumab reduced the risk of a first major cardiovascular event in high-risk patients with diabetes and no known significant atherosclerosis. The study does not describe adverse events or safety outcomes for this subgroup.

Key Takeaways

• This prespecified subgroup included 3,655 patients with diabetes and no known significant atherosclerosis within a placebo-controlled comparison added to statin therapy.
• In the lipid substudy, evolocumab was associated with lower LDL-C at 48 weeks, and in this prespecified subgroup analysis it was associated with lower rates of both major cardiovascular composite end points vs placebo.
• All-cause mortality was reported as lower with evolocumab; subgroup-specific adverse-event details were not provided in the abstract.