Evolocumab Cuts MACE Risk by 31% in High-Risk Diabetes Patients Without Prior Atherosclerosis, With Nicholas Marston, MD, MPH

Patients with diabetes have long been recognized as carrying cardiovascular risk comparable to those with established coronary artery disease (CAD). Yet despite this recognition, the intensity of lipid-lowering treatment recommended for persons with type 2 diabetes in primary prevention has historically lagged behind that reserved for secondary prevention populations—a discrepancy that a major new clinical trial now challenges directly.

“Historically, we have thought about diabetes as a CAD equivalent,” Nicholas Marston, MD, MPH, a preventive cardiologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, said in a recent interview at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana. “But, if you look at the guidelines, we aren't as aggressive with treating LDL cholesterol levels in patients with diabetes as we are in those who are secondary prevention with coronary disease, especially if they've had an event.”

The VESALIUS-CV trial, a randomized, double-blind, placebo-controlled study of approximately 12 000 patients, was designed to examine the cardiovascular benefit of evolocumab (Repatha; Amgen), a PCSK9 inhibitor monoclonal antibody, in patients at elevated cardiovascular risk who had not yet experienced a myocardial infarction or stroke.¹ Eligible participants were required to have either qualifying atherosclerosis or high-risk diabetes, along with an LDL cholesterol level exceeding 90 mg/dL despite background statin therapy. After 4.5 years of follow-up, the trial's overall results of a 25% reduction in MACE were published and presented last year at the ACC Scientific Sessions 2025, generating substantial attention in the preventive cardiology community.

In a new secondary analysis presented at the 2026 ACC Scientific Sessions, investigators examined outcomes specifically among participants with no known significant atherosclerosis, a subgroup comprised entirely of patients with diabetes by virtue of trial enrollment criteria. Dr Marston presented the findings and discussed their implications for practice. In a high-risk diabetes cohort, evolocumab reduced 3-point and 4-point MACE by 31%, with absolute risk reductions of 2.1% and 2.9% at 5 years, respectively. Reductions in cardiovascular death (32%), all-cause mortality (24%), MI, ischemic stroke, and ischemia-driven revascularization were consistent across all endpoints.²

The consistency and magnitude of these benefits, which span hard endpoints including mortality, distinguish these findings from prior data in primary prevention populations. The achieved median LDL-C in the evolocumab arm was approximately 44 mg/dL, well below the 70 mg/dL threshold currently recommended for persons at high-risk for developing type 2 diabetes in US guidelines.³

“The results demonstrate that clinicians should be treating patients more similarly, at least in terms of their LDL cholesterol goals,” Dr Marston added in the interview above.

Editors’ Note: Marston reports disclosures with Ionis, Lilly, Arrowhead, Janssen, Amgen, New Amsterdam, and others.

References:

1. O'Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease. Circulation. 2022;146:1109-1119. doi:10.1161/CIRCULATIONAHA.122.061620
2. Marston NA, Bohula EA, Bhatia AK, et al. Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. JAMA. Published online March 28, 2026. doi:10.1001/jama.2026.3277
3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:3168-3209. doi:10.1016/j.jacc.2018.11.002