Evolocumab Prevents Recurrent Cardiovascular Events Following MI or Stroke

Patients with a prior myocardial infarction (MI) or stroke who received evolocumab on top of statin therapy saw major reductions in the rate of total major adverse cardiovascular events (MACEs), based on a new subanalysis of the VESALIUS-CV trial.1

Presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Jose Nicolau, MD, PhD, professor at the University of São Paulo Medical School and senior investigator at Heart Institute InCor, this subanalysis addressed a gap in existing VESALIUS data. While the original trial only analyzed patients without prior MI or stroke, Nicolau and colleagues aimed to determine whether evolocumab exhibited a similar cardioprotective effect on patients who had already experienced an event.1,2

“The results of VESALIUS, the first results published in NEJM at the end of last year, showed wonderful results with a very important benefit with evolocumab versus placebo,” Nicolau told HCPLive in an exclusive interview. “But the patient, if they don’t die, very often has more than 1 event. That’s what we analyzed in this prespecified subanalysis of VESALIUS – we analyzed both first and subsequent events.”

VESALIUS-CV was a double-blind, randomized, placebo-controlled clinical trial conducted at 774 sites internationally. Patients were eligible if they had LDL-C ≥90 mg/dL, non-HDL-C ≥120 mg/dL, or apolipoprotein B ≥80 mg/dL. Additionally, patients needed to have significant coronary artery disease, atherosclerotic cerebrovascular disease, peripheral artery disease, or diabetes mellitus.2

Patients were randomly assigned in a 1:1 ratio to either 140 mg of evolocumab subcutaneously every 2 weeks or matching placebo. Primary endpoints included a composite of death from coronary heart disease, MI, or ischemic stroke (3-point MACE) and a composite of 3-point MACE and ischemia-driven arterial revascularization (4-point MACE).2

A total of 12,257 patients were enrolled, with 6129 assigned to evolocumab and 6128 to placebo. Over a median follow-up of 4.6 years, 3-point MACE events occurred in 336 patients in the evolocumab group versus 443 in the placebo group. A 4-point MACE event occurred in 747 patients receiving evolocumab versus 907 receiving placebo. The trial concluded with no evidence of a between-group difference for safety events.2

In the present analysis, Nicolau and colleagues analyzed total 3-P and 4-P MACE events, both first and subsequent, using a negative binomial regression model. All 12,257 patients from the original trial were included. By the end of the trial, 779 first 3-P MACE events and 146 subsequent events had occurred, for a total of 925 total events. For 4-P MACE, the team logged 1654 first events and 1107 subsequent events for 2761 total.1

Evolocumab reduced 3-P MACE risk by 25% (HR, 0.75; 95% CI, 0.65-0.86), recurrent events by 37% (incidence-ratio rate [IRR], 0.63; 95% CI, 0.42-0.94), and total events by 27% (IRR, 0.73; 95% CI, 0.63-0.86). Similarly, evolocumab reduced 4-P MACE first event risk by 19% (HR, 0.81; 95% CI, 0.73-0.89), recurrent events by 25% (IRR, 0.75; 95% CI, 0.61-0.91), and total events by 20% (IRR, 0.8; 95% CI, 0.71-0.9; P <.001).1

Based on these data, Nicolau and colleagues noted that, for every 1000 patients treated for 5 years, evolocumab prevented 20 first 3-P MACE events, 5 subsequent events, and 25 total events. For 4-P MACE, treatment with evolocumab prevented 31 initial events, 24 subsequent events, and 55 total events. These results were consistent across all subgroups, including by qualifying atherosclerosis and high-risk diabetes without atherosclerosis.1

Ultimately, the team concluded that evolocumab is not only efficacious in preventing recurrent MACEs but also saw nearly double the number of recurrent events prevented versus placebo compared to the analysis of only first events. Nicolau and colleagues presented these data as further support for the key role of LDL-C lowering in patients with atherosclerosis or high-risk diabetes, regardless of whether these patients have experienced a prior MI or stroke.1

“The fact is that, when you decrease the LDL-C in such a case with evolocumab, you are adding benefit. This is true for high-risk patients, people with previous MI or previous stroke,” Nicolau said. “But now, we are showing that this is also true for patients without previous MI or stroke. They are high risk, but not high high risk. This is a continuum, and we will continue to analyze and to study this population in the future.”

Editors’ Note: Nicolau reports disclosures with Amgen, AstraZeneca, Bayer, Novo Nordisk, Novartis, Janssen, and others.

References

1. Nicolau JS, Murphy S, Giugliano RP, et al. Reduction in total cardiovascular events with evolocumab in patients with no prior myocardial infarction or stroke: a pre-specified analysis of VESALIUS-CV. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

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