Evolocumab Significantly Reduces Major Cardiovascular Events

New research from the VESALIUS-CV trial indicates that adding evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, to existing high-intensity cholesterol-lowering therapies significantly reduces the risk of major cardiovascular events (MACE) among patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes. This finding was presented by Dr. Erin Bohula, assistant professor of medicine at Harvard Medical School, during the American Heart Association’s Scientific Sessions 2025 held in New Orleans, Louisiana.

The VESALIUS-CV trial was a large-scale, international study, involving 12,257 patients across 774 sites in 33 countries. Participants were aged between 50 to 79 years for men and 55 to 79 years for women, and had elevated LDL cholesterol levels. They were required to have been on stable, optimized lipid-lowering therapy for at least two weeks prior to enrollment, and those with a history of heart attack or stroke were excluded from the study.

Key Findings from the VESALIUS-CV Trial

Patients in the trial were randomly assigned to receive either subcutaneous evolocumab at a dose of 140 mg every two weeks or a matching placebo. The study aimed to evaluate two primary efficacy endpoints: a composite of death from coronary heart disease, myocardial infarction, or ischemic stroke (3-point MACE) and a composite that included ischemia-driven arterial revascularization (4-point MACE).

The results showed that evolocumab therapy was associated with a significant reduction in both primary efficacy endpoints. Specifically, a 3-point MACE event occurred in 336 patients receiving evolocumab compared to 443 patients in the placebo group, translating to a hazard ratio (HR) of 0.75, indicating a 25% lower risk (P < .001). Similarly, for the 4-point MACE, events were recorded in 747 patients on evolocumab versus 907 in the placebo arm, yielding an HR of 0.81, which corresponds to a 19% lower risk (P < .001).

Importantly, the trial found no significant difference in the incidence of adverse events leading to discontinuation between the two groups, suggesting that evolocumab is well-tolerated among this population.

Implications for Cardiovascular Health

Dr. Bohula emphasized that these findings mark the first demonstration of improved cardiovascular outcomes with a PCSK9 inhibitor in patients who have not experienced a prior heart attack or stroke but are already undergoing high-intensity lipid-lowering treatment. “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,” she added.

The VESALIUS-CV trial results, when combined with data from genetic studies and other outcomes studies involving PCSK9 inhibitors, suggest that long-term treatment with these medications can potentially improve cardiovascular morbidity and mortality over time.

As the research continues to unfold, the implications of these findings could reshape treatment protocols for patients at high risk of cardiovascular events, particularly those with ASCVD and diabetes, underscoring the importance of effective cholesterol management in preventing serious health complications.