Evolocumab Significantly Reduces Major Cardiovascular Events

A recent study presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, revealed that adding evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, to existing high-intensity cholesterol-lowering therapy markedly decreases the risk of first major cardiovascular events (MACE) in patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes. The findings from the VESALIUS-CV trial were delivered by Erin Bohula, MD, an assistant professor of medicine at Harvard Medical School and Brigham & Women’s Hospital.

The VESALIUS-CV trial, which was an international, double-blind, randomized, placebo-controlled study, involved 12,257 patients across 774 sites in 33 countries. Participants included men aged between 50 and 79 years and women aged 55 to 79 years, all with elevated LDL cholesterol levels of at least 90 mg/dL. To qualify, patients were required to be on stable, optimized lipid-lowering therapy for at least two weeks prior to enrollment and to have specific cardiovascular risk factors.

Patients were excluded if they had a history of myocardial infarction or stroke, ensuring the study focused on those without prior cardiovascular events. Eligible individuals had to meet criteria for conditions such as coronary artery disease, atherosclerotic cerebrovascular disease, peripheral artery disease, or high-risk diabetes, along with at least one additional risk factor, including age, smoking, or severely elevated lipid levels.

In the trial, patients were randomly assigned in a 1:1 ratio to receive either 140 mg of evolocumab subcutaneously every two weeks or a matching placebo. The primary efficacy endpoints included a composite measure of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a broader measure that added ischemia-driven arterial revascularization (4-point MACE).

The results indicated that evolocumab significantly lowered the risks of both primary endpoints when compared to placebo. A total of 336 patients in the evolocumab group experienced a 3-point MACE event, contrasted with 443 patients in the placebo group. This represented a hazard ratio of 0.75 with a 95% confidence interval (CI) of 0.65-0.86 and a p-value of less than 0.001, suggesting a 25% reduction in risk.

Similarly, for the 4-point MACE events, 747 patients in the evolocumab group experienced events compared to 907 patients in the placebo group, yielding a hazard ratio of 0.81 with a 95% CI of 0.73-0.89 and a p-value of less than 0.001, indicating a 19% lower risk.

Importantly, there were no significant differences in the incidence of adverse events leading to discontinuation between the two groups, suggesting that evolocumab is a well-tolerated addition to existing therapies.

Bohula emphasized the significance of these findings, stating, “Together with data from genetic studies of PCSK9 variants and other PCSK9 inhibitor outcomes studies, our findings suggest that long-term lowering with PCSK9 inhibitors can help to improve cardiovascular morbidity and potentially mortality over time. The findings also support the use of intensive LDL-C lowering to achieve targets of around 40 mg/dL to help prevent a first major cardiovascular event.”

The results of this trial could have profound implications for the treatment of patients at risk for cardiovascular events, particularly among those already on intensive cholesterol-lowering regimens.