Alirocumab for Stabilisation of Symptomatic Vulnerable Carotid Plaque

BACKGROUND: Symptomatic carotid stenosis of 50-69% carries a 30-day recurrent-stroke risk of 5-8% and a 2-year risk of 15-20% on best medical therapy alone. A substantial proportion of patients are either surgically deferred or anatomically borderline where revascularisation benefit is debated. PCSK9 inhibitors have demonstrated carotid plaque regression, reduction in lipid-rich necrotic core, and reduction in arterial inflammation. However, no RCT has tested whether PCSK9 inhibition can reduce intraplaque haemorrhage or LRNC in symptomatic carotid plaque. DESIGN: This is a phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group superiority trial with a 26-week primary endpoint assessment and a 52-week extension. Patients with recently symptomatic carotid stenosis (50-69%) with MRI-confirmed vulnerable plaque features (IPH or LRNC) will be randomised 1:1 to alirocumab 150 mg SC q2w or matched placebo, both on background high-intensity statin therapy. PRIMARY ENDPOINT: Absolute change in IPH volume (mm³) from baseline to week 26, measured on MPRAGE sequences by a blinded central imaging core lab using semi-automated segmentation. SECONDARY ENDPOINTS: Include percent change in LRNC volume, absolute change in minimum fibrous cap thickness, percent change in total plaque wall volume at weeks 26 and 52, composite of ipsilateral recurrent stroke or TIA through week 52, and proportion avoiding carotid revascularisation through week 52. SAFETY: Monitored by an independent Data and Safety Monitoring Board (DSMB) with pre-specified interim analyses at 50% and 75% enrolment.