Adjunctive PCSK9 Inhibitor Evolocumab in the Prevention of Early Neurological Deterioration in Non-cardiogenic Acute Ischemic Stroke: A Multicenter, Prospective, Randomized, Open-Label, Clinical Trial.

Summary

In a multicenter PROBE RCT (n=272) of non-cardiogenic AIS within 24 hours, evolocumab plus atorvastatin reduced early neurological deterioration versus atorvastatin alone (13.2% vs 24.3%; p=0.010), increased day-7 LDL-C target attainment (74.3% vs 14.7%; p=0.001), attenuated IL-6 rise, and improved 90-day functional outcomes (mRS ≤2: 83.1% vs 65.4%). Safety profiles were comparable.

Key Findings

• Early neurological deterioration was lower with evolocumab plus atorvastatin vs atorvastatin alone (13.2% vs 24.3%; p=0.010).
• LDL-C target attainment on day 7 was markedly higher with evolocumab (74.3% vs 14.7%; p=0.001).
• IL-6 increase over 7 days was attenuated in the evolocumab group (p=0.033), and 90-day mRS ≤2 was more frequent (83.1% vs 65.4%; p=0.001).

Clinical Implications

For selected AIS patients within 24 hours, adding evolocumab to high-intensity statin therapy may reduce early neurological worsening and improve short-term function. Larger double-blind trials are warranted before guideline adoption.

Limitations

• Open-label treatment may introduce performance bias.
• Modest sample size and single-country setting; primary follow-up limited to 7 days (clinical outcomes to 90 days).

Future Directions

Conduct large, double-blind, placebo-controlled global RCTs to confirm efficacy, assess imaging biomarkers (e.g., plaque/penumbra), and evaluate optimal timing/dosing and generalizability.