Evolocumab Cuts MACE by 29% in High-Risk Diabetes Without Prior MI or Stroke: Lawrence Leiter, MD

New data from a prespecified subgroup analysis of the VESALIUS-CV (NCT03872401) trial demonstrate that intensive low-density lipoprotein (LDL) cholesterol lowering with evolocumab (Repatha; Amgen) significantly reduces cardiovascular events in patients with high-risk diabetes who have not yet experienced a heart attack or stroke—findings presented at the American Diabetes Association (ADA) 2026 Scientific Sessions.

Lawrence Leiter, MD, director of the Lipid Clinic; associate director of the Clinical Nutrition and Risk Factor Modification Centre; associate scientist, Li Ka Shing Knowledge Institute at St. Michael’s Hospital; and professor in the departments of medicine and nutritional sciences at the University of Toronto, shared the results in an interview with The American Journal of Managed Care^®. The VESALIUS-CV trial enrolled approximately 12,000 patients with elevated cardiovascular risk and elevated LDL cholesterol despite statin therapy, with or without ezetimibe (Zetia; Merck, Schering-Plough), and no prior history of myocardial infarction (MI) or stroke. The subgroup analysis focused on roughly 6000 patients meeting criteria for high-risk diabetes—defined as having microvascular complications, chronic insulin use, or a diabetes duration of at least 10 years.

Adding evolocumab to background therapy achieved a median LDL of approximately 45 mg/dL, which is lower than many current guideline targets. This was associated with a 29% reduction in 3-point major adverse cardiovascular events (MACE), a 21% reduction in 4-point MACE, and a nominally significant 21% reduction in all-cause mortality.

Crucially, the cardiovascular benefits were consistent regardless of whether patients had qualifying atherosclerosis at baseline and regardless of concurrent use of sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists. Leiter emphasized that while these newer diabetes therapies provide important cardioprotection, they are not sufficient on their own.

"If you really want to minimize cardiovascular risk in these patients, we really have to add intensive LDL lowering to the mix," Leiter said.

The findings reinforce a comprehensive risk reduction approach in high-risk diabetes, targeting glucose, blood pressure, and LDL simultaneously, and support pushing toward lower LDL targets than guidelines currently recommend.