Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial.

Summary

In a prespecified subgroup of 3655 high-risk patients with diabetes but without known significant atherosclerosis, evolocumab reduced first MACE (HR 0.69 for both 3- and 4-point MACE) over a median 4.8 years and lowered all-cause mortality (HR 0.76). LDL-C fell to a median 52 mg/dL at 48 weeks versus 111 mg/dL with placebo.

Key Findings

• Evolocumab reduced 5-year 3-point MACE (HR 0.69; P=0.009) and 4-point MACE (HR 0.69; P=0.001) versus placebo.
• All-cause mortality was lower with evolocumab (HR 0.76; 5-year KM 7.8% vs 10.1%).
• LDL-C reduction at 48 weeks was substantial (median 52 mg/dL vs 111 mg/dL in placebo) on top of statins.

Clinical Implications

For high-risk patients with diabetes lacking known significant atherosclerosis, adding evolocumab to statins can reduce first MACE; clinicians may consider PCSK9 inhibition for primary prevention in this population after individualized risk–benefit assessment and cost/access considerations.

Limitations

• Findings derive from a prespecified subgroup; external generalizability beyond similar high-risk diabetes populations requires caution.
• Cost-effectiveness and adherence in real-world primary prevention settings were not addressed.

Future Directions

Define optimal selection criteria and cost-effectiveness for primary prevention with PCSK9 inhibitors in diabetes; assess effects in broader non-atherosclerotic high-risk groups and explore de-escalation strategies once LDL-C targets are achieved.