Evolocumab reduces MACE risk in patients with diabetes without known atherosclerosis
ACC.26 – In a secondary analysis of VESALIUS-CV among patients with diabetes without known significant atherosclerosis, evolocumab reduced the risk of first MACE compared with placebo.
This summary is based on the presentation of Nicholas Marston, MD (Boston, MA, USA) at the ACC.26 Scientific Session - Evolocumab in Patients Without Known Atherosclerosis and With Diabetes: Secondary Analysis From VESALIUS-CV.
Introduction and methods
The VESALIUS-CV (The Effect of EVolocumab in PatiEntS at High CArdiovascuLar RIsk WithoUt Prior Myocardial Infarction or Stroke) trial previously demonstrated that evolocumab reduces the risk of MACE in patients with atherosclerosis or diabetes but with no previous MI or stroke. In this secondary analysis of VESALIUS-CV, the authors evaluated the effects of evolocumab versus placebo in patients without known atherosclerosis and with diabetes.
The VESALIUS-CV 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). Patients had an LDL-c of ≥90 mg/dL, non-HDL-c of ≥120 mg/dL or apoB of ≥80 mg/dL. This secondary analysis included 3,655 patients (30% from VESALIUS-CV) without known significant atherosclerosis and with diabetes. Median follow-up was 4.8 years.
The dual primary endpoints were 3-point MACE, a composite of CHD death, MI or ischemic stroke, and 4-point MACE, a composite of CHD death, MI, ischemic stroke or ischemia-driven arterial revascularization.
Main results
- At 48 weeks, the median LDL-c level was 52 mg/dL in the evolocumab group and 111 mg/dL in the placebo group. At 96 weeks, the levels were 44 mg/dL and 105 mg/dL, respectively.
- At 5 years, evolocumab reduced the risk of 3-point MACE compared with placebo by 31% (HR: 0.69; 95%CI: 0.52–0.91; P=0.009; absolute risk reduction: 2.1%).
- At 5 years, evolocumab also reduced the risk of 4-point MACE compared with placebo (HR: 0.69; 95%CI: 0.55–0.86; P=0.001; absolute risk reduction: 2.9%).
- The rate of CV death was reduced in the evolocumab group compared with the placebo group (2.6% vs. 4.0%; HR: 0.68; 95%CI: 0.46–0.99; P=0.046).
- Evolocumab reduced the rate of all-cause mortality compared with placebo (7.8% vs. 10.1%; HR: 0.76; 95%CI: 0.61–0.95; P=0.017).
Conclusion
In patients without known atherosclerosis and with diabetes, evolocumab reduced the risk of first MACE compared with placebo. Dr. Marston concluded that “these data strongly support that in these lower-risk patients we should be targeting LDL-c goals typically reserved for very high-risk secondary prevention patients.”
- Our reporting is based on the information provided at the ACC.26 Scientific Session -