Add-On PCSK9 Inhibitor Therapy for Acute Stroke Attributable to Intracranial Atherosclerosis: A Randomized Clinical Trial

Why clinicians should know about it

• Picked for Neurology (clinical) (paper of the day, 10 September 2026): Randomized trial of PCSK9 inhibitor in intracranial atherosclerosis stroke

Abstract

BACKGROUND: Intracranial atherosclerotic stenosis is a major cause of ischemic stroke with high recurrence rates despite intensive therapy. The efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) as adjunctive treatment in intracranial atherosclerotic stenosis remains unclear. METHODS: We conducted a prospective, randomized, open-label, blinded-end point trial involving 62 patients with symptomatic intracranial atherosclerotic stenosis. Participants were randomized 1:2 to receive either a PCSK9i (alirocumab 75 mg every 2 weeks) plus high-intensity statin or high-intensity statin alone for 6 months. The primary outcome was the change in intracranial artery stenosis measured by high-resolution vessel-wall magnetic resonance imaging. Secondary outcomes included plaque enhancement volume, low-density lipoprotein cholesterol target achievement (<55 mg/dL), recurrent stroke events, modified Rankin Scale, and safety assessments. RESULTS: Among 62 participants (median age, 66 years; 77% men), 60 completed the study per protocol. At 6 months, median stenosis reduction was greater in the PCSK9i group (7.1%; interquartile range, 3.6-12.8%) than in controls (-1.2%; interquartile range, -4.9-4.5%) (P<0.001). The baseline-adjusted mean difference estimated using a generalized linear model was 8.9 percentage points (95% CI, 5.1-12.6). Both groups showed significant reduction in plaque enhancement volume, but between-group difference was not significant (4.3 versus 4.0 mm3; P=0.79). Low-density lipoprotein cholesterol <55 mg/dL was achieved in 85% of the PCSK9i group versus 13% of controls (P<0.01). Recurrent stroke occurred in 5% versus 13% of patients (P=0.34). No serious adverse events were reported in either group. CONCLUSIONS: In patients with symptomatic intracranial atherosclerotic stenosis, adjunctive PCSK9i therapy significantly reduced intracranial stenosis and improved low-density lipoprotein cholesterol control over 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05001984.

Abstract as published, via PubMed.