The addition of evolocumab to background lipid-lowering therapy significantly reduced the risk of a first major cardiovascular event in high-risk patients with diabetes but no prior myocardial infarction or stroke, according to research presented at the American College of Cardiology’s Annual Scientific Session & Expo and simultaneously published in JAMA.1,2
The findings from the VESALIUS-CV trial extend the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition beyond secondary prevention populations, suggesting potential benefit earlier in the atherosclerotic cardiovascular disease (ASCVD) continuum.
“For over a decade, the intensive cholesterol‑lowering have been reserved for patients who already have cardiovascular disease,” corresponding author Nicholas A. Marston, MD, MPH, a cardiologist with the Mass General Brigham Heart and Vascular Institute, said in a press release. “These results demonstrate the benefit of intensive lowering cholesterol earlier and should change how we think about the prevention of heart attacks, strokes, and heart disease in patients without known significant atherosclerosis.”3
Significant Reduction in Major Adverse Cardiovascular Events
Over a median follow-up of approximately 5 years, a 4-point major adverse cardiovascular event (MACE) occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (10.5%) in the placebo group (hazard ratio [HR], 0.69; 95% CI, 0.55-0.86; P = .001), representing an absolute risk reduction of 2.9%.
All-cause mortality was also lower with evolocumab, occurring in 136 patients (7.8%) compared with 172 patients (10.1%) in the placebo group (HR, 0.76; 95% CI, 0.61-0.95).
The primary composite endpoint included coronary heart disease death, myocardial infarction, ischemic stroke, and ischemia-driven revascularization.
Shifting LDL-C Management Earlier in the Disease Course
Historically, intensive LDL-C lowering strategies—including PCSK9 inhibitors—have been reserved for secondary prevention following myocardial infarction or stroke.
This trial is among the first to demonstrate that adding a PCSK9 inhibitor in patients without prior ASCVD but at high cardiovascular risk can reduce first events, supporting earlier intervention.
The study specifically evaluated patients with diabetes, a population known to carry elevated cardiovascular risk even in the absence of established ASCVD.
For primary care clinicians managing cardiometabolic risk, these findings suggest that earlier intensification of LDL-C–lowering therapy may be warranted in select high-risk patients—particularly those with diabetes and elevated residual risk despite statin therapy.
Current guidelines have emphasized aggressive LDL-C targets primarily in secondary prevention settings; however, the present findings support consideration of similar targets earlier in the disease trajectory.
Clinical Takeaways for Primary Care
- PCSK9 inhibition in primary prevention: Evolocumab reduced first MACE by 31% (HR, 0.69) in high-risk patients with diabetes without prior ASCVD.
- Absolute risk reduction: 2.9% over ~5 years (7.6% vs 10.5%).
- Mortality benefit observed: All-cause death reduced (HR, 0.76).
- Independent implication: Supports intensifying LDL-C lowering earlier, not just after a CV event.
- Target population: Patients with diabetes and elevated CV risk despite standard therapy.
- Practice consideration: Incorporate earlier risk stratification and consider nonstatin therapy escalation in appropriate patients.
Limitations and Future Considerations
Investigators noted that some analyses were prespecified subgroup evaluations, and prospective validation of these findings is warranted.
Further research is needed to determine optimal patient selection, cost-effectiveness, and long-term outcomes associated with earlier use of PCSK9 inhibitors in primary prevention populations.
References:
- 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.
- 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
- Mass General Brigham. Targeted Cholesterol-Lowering Therapy Can Prevent First Heart Attack or Stroke in High-Risk Patients with Diabetes. News release. March 28, 2026. Accessed March 30, 2026. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/cholesterol-lowering-therapy-for-heart-attack-stroke-prevention-diabetic-patients
