Evolocumab reduces MACE in high CVD risk patients with no prior MI or stroke
AHA 2025 – In VESALIUS-CV among patients with atherosclerosis or diabetes but with no previous MI or stroke, evolocumab treatment, in addition to lipid-lowering therapy, led to a reduced risk of first MACE compared with placebo.
This summary is based on the presentation of Erin Bohula, MD (Boston, MA, USA) at the AHA Scientific Sessions 2025 - Effect of Evolocumab in Patients at High Cardiovascular Risk without Prior Myocardial Infarction or Stroke: Primary Results of the VESALIUS-CV trial.
Introduction and methods
PCSK9 inhibitors reduce the risk of MACE in patients with a previous major ASCVD event, such as MI or stroke. However, it is unknown whether PCSK9 inhibition is also clinically beneficial in patients with high CVD risk but with no prior MI or stroke. The VESALIUS-CV (The Effect of EVolocumab in PatiEntS at High CArdiovascuLar RIsk WithoUt Prior Myocardial Infarction or Stroke) trial was an international, double-blind, placebo-controlled, phase 3 RCT in which 12,257 stable patients with coronary artery disease with no MI, cerebrovascular disease with no stroke, peripheral artery disease, or high-risk diabetes were randomized to evolocumab 140 mg every 2 weeks or placebo, in addition to optimized lipid-lowering therapy (LLT). Inclusion criteria included LDL-c ≥90 mg/dL (≥2.3 mmol/L), non–HDL-c ≥120 mg/dL (≥3.1 mmol/L), or apoB ≥80 mg/dL (≥1.56 µmol/L). Median follow-up duration was 4.6 years. The dual primary endpoints were a composite outcome of time to CHD death, MI, or ischemic stroke (3-point MACE) and a composite outcome of time to 3-point MACE or ischemia-driven arterial revascularization (4-point MACE).
Main results
- The cumulative incidence of 3-point MACE was 6.2% in patients treated with evolocumab and 8.0% in placebo-treated patients (HR: 0.75; 95%CI: 0.65–0.86; P<0.0001).
- The risk of 4-point MACE was also lower in the evolocumab group than the placebo group (13.4% vs. 16.2%; HR: 0.81; 95%CI: 0.73–0.89; P<0.0001).
- In addition, the rate of all-cause mortality (one of the key secondary endpoints) was reduced in the evolocumab group compared with the placebo group (7.9% vs. 9.7%; HR: 0.80; 95%CI: 0.70–0.91; P=0.0005).
- A lipid substudy (n=2014) showed evolocumab treatment lowered the median LDL-c level from 115 mg/dL (IQR: 94–143) at baseline to 45 mg/dL (IQR: 26–73) at 48 weeks, compared with a reduction to 109 mg/dL (IQR: 86–144) in the placebo group (absolute reduction: 63 mg/dL; relative reduction: 55%; P<0.0001).
Conclusion
In patients at high CVD risk but with no previous MI or stroke, the addition of evolocumab to LLT led to a reduced risk of first MACE compared with placebo. Dr. Bohula concluded that these study results “support intensive LDL-c lowering to ~40 mg/dL, even in patients without a prior event.”
- Our reporting is based on the information provided at the AHA Scientific Sessions 2025 -