VESALIUS-CV: Evolocumab Prevents Cardiovascular Disease in High-Risk Diabetes

The phase 3 VESALIUS-CV trial has shown that evolocumab protects against cardiovascular disease in at-risk patients with type 2 diabetes (T2D) who have not experienced a myocardial infarction (MI) or stroke prior to screening, hinting at a new treatment pathway for cardiovascular disease.^1,2

These data were discussed at the American Society for Preventive Cardiology (ASPC) 2026 Congress on Cardiovascular Disease Prevention in Scottsdale, Arizona, by Marc Bonaca, MD, MPH, executive director at CPC Clinical Research, director of vascular research at the University of Colorado Anschutz, and a cardiologist with Brigham and Women’s Hospital and the VA Boston Healthcare System.

“VESALIUS moved backwards in terms of risk,” Bonaca told HCPLive in an exclusive interview. “It included patients who were either at high risk without known atherosclerotic vascular disease, or those who had it but who had not yet had an event. VESALIUS really asked the question of whether PCSK9 inhibition benefits patients who are at high risk or have the disease but haven’t yet experienced an event.”

The Structure of VESALIUS-CV

VESALIUS-CV was a double-blind, randomized, placebo-controlled, multicenter phase 3 study examining evolocumab’s impact on MACEs in patients at high cardiovascular risk without prior MI or stroke. The study was conducted across 852 locations worldwide and ultimately enrolled over 6000 patients. To be eligible for inclusion, patients needed to be ≥50 years (men) or ≥55 years (women) and <80 years and have LDL-C ≥90 mg/dL, non-HDL-C ≥120 mg/dL, or apolipoprotein B ≥80 mg/dL. Additionally, patients were required to meet ≥1 of the following at screening:

• Significant coronary artery disease (CAD)
• Significant atherosclerotic cerebrovascular disease
• Significant peripheral arterial disease
• Diabetes mellitus²

Patients were excluded from the trial if they had experienced an MI or stroke prior to randomization, had undergone coronary artery bypass grafting (CABG) <3 months before surgery, or eGFR <15 mL/min/1.73m², among other criteria. The primary outcomes were the number of patients experiencing coronary heart disease (CHD), MI, or ischemic stroke, whichever occurred first, as well as the number of patients experiencing CHD death, MI, ischemic stroke, or any ischemia-driven arterial revascularization, whichever occurred first.²

The team ultimately enrolled 6002 patients with high-risk diabetes. Of these, 67% were on a high-intensity statin, and 24% were on an SGLT2 inhibitor or a GLP-1 receptor agonist at baseline. Median LDL-C at 48 weeks was 47 mg/dL and 109 mg/dL in the evolocumab and placebo arms, respectively (P <.0001).¹

Findings from VESALIUS-CV

Following a median follow-up of 4.6 years, evolocumab was found to have decreased the relative rates of 3-point MACE and 4-point MACE by 29% (HR, 0.71; 95% CI, 0.59-0.86; P = .0004) and 21% (HR, 0.79; 95% CI, 0.69-0.91; P = .0013), respectively. Additionally, these findings were consistent irrespective of the presence or absence of atherosclerosis, baseline LDL-C, statin treatment intensity, and SGLT2 inhibitor or GLP-1 RA use. Investigators noted that the proportion of patients with all-cause mortality was 8.8% in the evolocumab arm versus 11% in the placebo arm (HR, 0.79; 95% CI, 0.67-0.93).¹

Ultimately, investigators concluded that evolocumab effectively reduced the rate of cardiovascular events in this patient cohort, regardless of the background use of other protective agents or the presence or absence of qualifying atherosclerosis.¹

“The field is shifting as we become much more sophisticated about understanding atherosclerosis,” Bonaca said. “If you think about it, for cancer screenings, we don’t wait for people to become symptomatic to treat them, and we don’t treat them based on guessing whether or not they have disease. We image – we conduct colonoscopies, mammograms, biopsies, and we treat accordingly. And for the number one killer in the world, cardiovascular disease, we now have tools that allow a much more sophisticated approach.”

Editors’ Note: Bonaca reports disclosures with Abbott, Amgen, BMS, Merck, NovoNordisk, Sanofi, and others.

References

1. Leiter LA, Giugliano RP, Marston NA, et al. Evolocumab in patients with high-risk diabetes: Results from the vesalius-CV trial. Diabetes Care. 2026;49(8):1366-1373. doi:10.2337/dc26-0847

2. Amgen. Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV). ClinicalTrials.gov Identifier: NCT03872401. Updated June 25, 2026. Accessed https://clinicaltrials.gov/study/NCT03872401