Evolocumab in Patients With High-Risk Diabetes: Results From the VESALIUS-CV Trial

OBJECTIVE: This prespecified analysis of Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV) evaluated the efficacy of the PCSK9 inhibitor evolocumab for preventing first cardiovascular events in patients with high-risk diabetes. RESEARCH DESIGN AND METHODS: VESALIUS-CV randomized patients with high-risk diabetes (microvascular disease, insulin use, or duration ≥10 years) or qualifying atherosclerosis, but no prior myocardial infarction (MI) or stroke, and LDL cholesterol (LDL-C) ≥90 mg/dL to evolocumab 140 mg or matching placebo every 2 weeks. The dual primary end points were a composite of coronary heart disease death, MI or ischemic stroke (three-point major adverse cardiovascular event [3P-MACE]) and 3P-MACE plus ischemia-driven arterial revascularization (four-point [4P]-MACE). RESULTS: Of the 6,002 patients with high-risk diabetes, 67% were on a high-intensity statin and 24% were on a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) at baseline. The median LDL-C at 48 weeks was 47 mg/dL and 109 mg/dL in the evolocumab and placebo arms, respectively (P < 0.0001). After a median follow-up of 4.6 years, evolocumab decreased the relative rates of 3P-MACE and 4P-MACE by 29% (hazard ratio [HR] 0.71; 95% CI 0.59, 0.86; P = 0.0004) and 21% (HR 0.79; 95% CI 0.69, 0.91; P = 0.0013), respectively. These findings were consistent regardless of the presence or absence of qualifying atherosclerosis, baseline LDL-C, statin intensity, and SGLT2i or GLP-1RA use (Pint > 0.05 for each). The porportion of patients with all-cause death was 8.8% vs. 11.0% in the evolocumab versus placebo arms (HR 0.79; 95% CI 0.67, 0.93). CONCLUSIONS: Evolocumab reduced the rate of cardiovascular events in patients with high-risk diabetes, regardless of the presence or absence of qualifying atherosclerosis and background use of other cardioprotective agents.