Evolocumab Reduces CV Risk in Non-Atherosclerotic Patients With Diabetes, With Nicholas Marston, MD, MPH

Evolocumab has the capacity to reduce the risk of first major cardiovascular event (MACE) in patients without known significant atherosclerosis and with diabetes, according to a secondary analysis of the VESALIUS-CV trial.1,2

Presented at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana, by Nicholas Marston, MD, MPH, a preventive cardiologist at Brigham and Women’s Hospital and an assistant professor of medicine at Harvard Medical School, these data highlight the investigational oral PCSK9 inhibitor’s capacity for expanding treatment to patients without a history of major cardiovascular events. The analysis demonstrates the importance of targeting lower LDL-C goals across high-risk primary patients.2

“We often think about diabetes as a CAD equivalent,” Marston told HCPLive in an exclusive interview. “But if you look at the guidelines, we aren’t as aggressive with treating LDL-C levels in patients with diabetes as we are in those who are secondary prevention with coronary disease, especially if they’ve had an event. I think these results demonstrate that we really should be treating them more similarly, at least in terms of their LDL-C goals.”

VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab, involving 12,257 patients with qualifying atherosclerosis or high-risk diabetes. The latter was defined as ≥10 years’ duration, daily insulin use, or microvascular disease. Eligible patients also had to present with no prior myocardial infarction or stroke, an LDL-C level ≥90 mg/dL, a non-HDL-C level ≥120 mg/dL, and an apolipoprotein-B (apoB) level ≥80 mg/dL.2

In the present analysis, Marston and colleagues examined outcomes in patients without known significant atherosclerosis, which was defined as any arterial stenosis ≥50% or CAC ≥100. The study included dual primary endpoints – the first was a composite of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE), while the other was 3-P MACE plus ischemia-driven arterial revascularization (IDR) (4-P MACE). Secondary endpoints included the following composites:

• Myocardial infarction, ischemic stroke, or IDR
• Coronary heart disease death, myocardial infarction, or IDR
• Cardiovascular death, myocardial infarction, or ischemic stroke
• Coronary heart disease death or myocardial infarction1,2

The sub-analysis cohort included a total of 3655 patients with a median age of 65 years, followed for a median of 4.8 years. Median body mass index was 31.4 (interquartile range [IQR], 28-35.6), most patients had hypertension, and nearly all patients had diabetes. The median baseline LDL-C level was 132 mg/dL (IQR, 108-156).2

Ultimately, a 3-P MACE occurred in 83 patients in the evolocumab group compared to 117 in placebo (HR, 0.69; 95% CI, 0.52-0.91; P = .009; between-group risk difference, 2.1%; 95% CI, 0.4-3.8%). A 4-P MACE occurred in 127 patients in the evolocumab group versus 178 in the placebo group (HR, 0.69; 95% CI, 0.55-0.86; P = .001; between-group risk difference, 2.9%; 95% CI, 0.9-4.9%). Evolocumab’s effect was also more apparent after the first year of treatment, with 41% (HR, 0.59; 95% CI, 0.43-0.81) and 39% (HR, 0.61; 95% CI, 0.48-0.79) reductions in the risk of 3- and 4-P MACE afterwards, respectively.2

“Because this patient population was high-risk primary prevention with diabetes, we do have to keep that caveat in terms of generalizability; however, I think we can certainly say that these data support intensifying treatment and LDL-C goals in those patients,” Marston said. “Really, what we should be doing is treating these high-risk diabetes patients to the kind of targets that we reserve for secondary prevention.”

Editors’ Note: Marston reports disclosures with Ionis, Lilly, Arrowhead, Janssen, Amgen, New Amsterdam, and others.

References

1. Marston N, Bohula E, Bhatia A, et al. Evolocumab Reduces Risk of First Major Cardiovascular Events by 31% in Patients Without Significant Atherosclerosis: Results from VESALIUS-CV. Abstract presented at the American College of Cardiology Scientific Sessions 2026, New Orleans, LA. March 28-30, 2026.

2. Marston NA, Bohula EA, Bhatia AK, et al. Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial. JAMA. Published online March 28, 2026. doi:10.1001/jama.2026.3277