JAMA

ACC 2026: PCSK9 inhibitor lowers first-time CV events in high risk diabetes without known atherosclerosis

March 31, 2026

Clinical takeaway: For patients with high‑risk diabetes and persistently elevated LDL‑C despite statins, consider earlier intensification with PCSK9 inhibitor therapy to prevent a first major cardiovascular event.

In a prespecified subgroup analysis of the VESALIUS‑CV trial, published in JAMA and presented at ACC.26, adding the PCSK9 inhibitor evolocumab to optimally tolerated statin therapy significantly reduced first major cardiovascular events in patients with diabetes but no known significant atherosclerosis. The analysis included 3,655 adults with high‑risk diabetes (LDL‑C ≥90 mg/dL) and no prior MI or stroke. Over a median 4.8 years, evolocumab lowered LDL‑C to a median of ~52 mg/dL and reduced the risk of 3‑point MACE (CV death, MI, or ischemic stroke) by 31% vs. placebo (hazard ratio, 0.69; absolute risk reduction, ~2%). A similar reduction was seen for a broader composite including ischemia‑driven revascularization. Exploratory analyses suggested lower CV and all‑cause mortality, with a safety profile consistent with prior studies. These findings extend evidence for aggressive LDL‑C lowering into high‑risk primary prevention populations and may prompt reconsideration of treatment thresholds in diabetes.

Source:

Marston NA, et al; VESALIUS-CV Investigators. (2026, March 28). JAMA. Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. https://pubmed.ncbi.nlm.nih.gov/41903215/