ESC Congress 2026: Evolocumab survival signal emerges before a first MI or stroke

Clinical takeaway: Consider adding evolocumab for patients with atherosclerosis or high-risk diabetes, no prior MI or stroke, and persistently elevated LDL-C despite background lipid-lowering therapy; potential survival benefits may require sustained treatment.

Although PCSK9 inhibitors prevent cardiovascular events, their effect on mortality in patients without a prior major event has been uncertain, partly because survival curves may take years to separate.

In this prespecified secondary analysis of VESALIUS-CV, presented at ESC 2026 in Munich and published in Circulation, 12,257 patients with qualifying atherosclerosis or high-risk diabetes and LDL-C of at least 90 mg/dL were randomized to evolocumab 140 mg every 2 weeks or placebo. Participants had no previous MI or stroke and were followed for a median of 4.6 years.

At 5 years, all-cause mortality was 7.9% with evolocumab versus 9.7% with placebo, an absolute difference of 1.8 percentage points and a 20% lower relative rate. Cardiovascular death was 21% lower (2.8% vs 3.6%), while noncardiovascular death was directionally 15% lower (4.2% vs 5.0%); benefits were generally consistent across demographic and clinical subgroups.

Mortality rates did not differ during the first 1.5 years, but were 27% lower with evolocumab thereafter. Modeling suggested that approximately 78% of the observed reduction in noncardiovascular deaths could be linked to prevention of preceding nonfatal MI, ischemic stroke, or revascularization, an association that does not establish causality.

“These analyses reinforce that a patient's first major cardiovascular event is not merely an isolated occurrence, but often a transition to a higher risk state,” said study coauthor Marc S. Sabatine, MD, MPH. “By preventing these events, evolocumab can alter the patient's trajectory, with lower rates of all-cause mortality.”

Source: Giugliano RP, et al. (2026 Aug 31) Circulation. Effects of Evolocumab on Mortality Outcomes in Patients Without Previous Myocardial Infarction or Stroke: A Prespecified Analysis of the VESALIUS-CV Randomized Clinical Trial