Evolocumab improves cardiovascular outcomes in patients with high-risk diabetes without significant atherosclerosis

Evolocumab versus placebo significantly improved outcomes for coronary heart disease death, myocardial infarction, and ischaemic stroke in patients with high-risk diabetes and no significant atherosclerosis.

Prof. Nicholas Marston (Harvard Medical School, MA, USA) presented data from VESALIUS-CV (NCT03872401), a phase 3, randomised 1:1, controlled trial evaluating evolocumab versus placebo on background of statin therapy in stable patients at high risk of cardiovascular events but without prior myocardial infarction or stroke. Patients were eligible if they had qualifying atherosclerotic risk factors and/or high-risk diabetes. The dual primary endpoints were 3-point major adverse cardiovascular events (MACE; time to coronary heart disease death, myocardial infarction, or ischaemic stroke) and 4-point MACE (3-point MACE plus ischaemia-driven arterial revascularisation). The presented analysis focused on patients with no significant atherosclerosis (n=3,655) and high-risk diabetes [1].

In this subgroup, evolocumab significantly prolonged the time to 3-point MACE compared with placebo, corresponding to a 31% relative risk reduction and a 2.1% absolute reduction. Evolocumab also significantly reduced 4-point MACE (absolute risk reduction, 2.9%; HR 0.69; 95% CI 0.55-0.86; P=0.001). The benefit of evolocumab was maintained for cardiovascular death (cumulative incidence 2.6% vs 4.0% at 5 years) and all-cause mortality (cumulative incidence 7.8% vs 10.1% at 5 years) [1]. The incidence of adverse events was similar between treatment groups [2].

In summary, VESALIUS-CV demonstrated significant reductions in MACE among high-risk primary-prevention patients with diabetes who had no known significant atherosclerosis. “The benefits observed in this subgroup support earlier intensification of lipid-lowering therapy beyond statins in the atherosclerotic cardiovascular disease continuum,” concluded Prof. Marston. “These data further suggest that, even in lower-risk patients, LDL-C targets typically reserved for very high-risk secondary prevention populations may be appropriate” [1].

Marston N, et al. Evolocumab in patients without significant atherosclerosis: Results from VESALIUS-CV. ACC 2026, 28–30 March, New Orleans, LA, USA.
Bohula EA, et al. N Engl J Med. 2026;394(2):117-127.