Evolocumab Improves Survival in Patients Without Prior MI or Stroke

Evolocumab substantially improves survival in high-risk patients without a prior myocardial infarction (MI) or stroke, according to a new subanalysis of VESALIUS-CV.1

These data were presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Robert Giugliano, MD, professor of medicine at Harvard Medical School and a physician at Brigham & Women’s Hospital.1

“If you start a cholesterol-lowering medicine today, you’re not going to prevent a death tomorrow, or in a week, or in a month, or even in a year. It takes a while. You’re affecting the underlying pathology,” Giugliano told HCPLive in an exclusive interview. “You’re changing the plaque, but it takes a while for that to translate into a reduction in death. So, we have to treat patients for a lifetime.”

The original VESALIUS-CV trial was an international, double-blind, randomized, placebo-controlled trial across 774 sites in 33 countries. Patients were eligible for inclusion if they were 50-79 years of age in men or 55-79 years of age in women and had an LDL-C level of ≥90 mg/dL, a non-HDL-C level of ≥120 mg/dL, or an apolipoprotein B level ≥80 mg/dL. Additionally, patients were required to be on stable, optimized lipid-lowering therapy for ≥2 weeks.2

Patients were assigned in a 1:1 ratio to either evolocumab 140 mg every 2 weeks or matching placebo. The 2 primary efficacy endpoints were a composite of death from coronary heart disease, MI, or ischemic stroke (3-point major adverse cardiovascular event [MACE]) and a composite of 3-point MACE and ischemia-driven arterial revascularization. Secondary endpoints included each individual component and composites of pairs of each component.2

A total of 12,257 patients were assigned to receive either evolocumab (n = 6129) or placebo (n = 6128), with a median age of 66 years and 43% women. After a median follow-up of 4.6 years, 3-point MACE events occurred in 336 patients in the evolocumab group and 443 in the placebo group (HR, 0.75; 95% CI, 0.65-0.86; P <.001), and 4-point MACE events occurred in 747 patients in the evolocumab group versus 907 in the placebo group (HR, 0.81; 95% CI, 0.73-0.89; P <.001).2

The present study was a prespecified secondary analysis of the VESALIUS-CV trial, incorporating all 12,257 patients from the original trial. Giugliano and colleagues evaluated the effects of evolocumab for all-cause mortality and cause-specific death, including cardiovascular disease, non-cardiovascular disease, and deaths of undetermined etiology. Cardiovascular death was further subcategorized as acute MI, sudden cardiac death, heart failure, cardiovascular hemorrhage, cardiovascular procedures, or other cardiovascular causes.1

During the 4.6-year follow-up, 973 patients died. Patients who died were more likely to be older at baseline with a higher prevalence of high-risk diabetes and kidney dysfunction. Of the 973 deaths, 351 (36%) were adjudicated as attributable to cardiovascular causes, 497 (51%) were non-cardiovascular, and 125 (13%) were of undetermined cause. The most frequent causes of cardiovascular death were sudden cardiac death (n = 174), heart failure (n = 58), acute MI (n = 44), and stroke (n = 39), representing 50%, 17%, 13%, and 11% of all cardiovascular deaths, respectively.1

Evolocumab nominally reduced the rate of all-cause mortality by 20% - among the evolocumab group, 434 patients died (5-year Kaplan-Meier rate, 7.9%), compared to 539 deaths in the placebo arm (9.7%) (HR, 0.8; 95% CI, 0.7-0.91; P = .0005). There was no reduction in mortality endpoints in the first 1.5 years (HR, 0.99; 95% CI, 0.78-1.25), according to landmark analyses; this was followed by a 27% reduction thereafter (HR, 0.73; 95% CI, 0.63-0.85).1

Giugliano and colleagues ultimately concluded that these data support the use of evolocumab to improve survival in patients without prior MI or stroke, particularly among those with high-risk diabetes without qualifying atherosclerosis. However, the implementation of this treatment, Giugliano acknowledges, will likely face the same limitations as other lipid-lowering therapies.1

“A large gap in background treatment of hyperlipidemias persists even in patients at high risk, patients who have known, diagnosed coronary disease, or cerebrovascular disease, or peripheral arterial disease, or high-risk diabetes,” Giugliano said. “We need to do a better job at reducing LDLs across the board, particularly in those patients at high risk.”

Editors’ Note: Giugliano reports disclosures from Amgen, Daiichi-Sankyo, Inventiva Pharma, Novartis, Pfizer, Sanofi, and others.

References

1. Giugliano RP, Bohula EA, Bellavia A, et al. Effects of evolocumab on mortality outcomes in patients without previous myocardial infarction or stroke: A prespecified analysis of the VESALIUS-CV randomized clinical trial. Circulation. Published online August 31, 2026. doi:10.1161/circulationaha.126.082436

2. Bohula EA, Marston NA, Bhatia AK, et al. Evolocumab in patients without a previous myocardial infarction or stroke. New England Journal of Medicine. 2026;394(2):117-127. doi:10.1056/nejmoa2514428