Early Aggressive Strategy for Treatment of Lipid-Lowering in Acute Ischemic Stroke Delivered With Endovascular Therapy for Large Artery Occlusion

Overview

EAST-LDL is a prospective, multicenter, randomized, open-label clinical trial with blinded endpoint assessment evaluating whether early intensive lipid lowering with the PCSK9 inhibitor recaticimab, administered before endovascular therapy, improves functional outcome in patients with acute ischemic stroke due to anterior-circulation large-vessel occlusion. Participants are randomized to recaticimab plus guideline-recommended standard of care or standard of care alone. The primary outcome is favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at 90 ± 7 days.

EAST-LDL is an investigator-initiated, prospective, multicenter, randomized, open-label clinical trial with blinded endpoint assessment conducted at approximately 20 stroke centers in China. Adults with acute ischemic stroke due to anterior-circulation large-vessel occlusion who are planned to undergo endovascular therapy within 24 hours of symptom onset or last known well are randomized 1:1 to the PCSK9 inhibitor group or the control group. Participants assigned to the PCSK9 inhibitor group receive guideline-recommended standard of care plus recaticimab 450 mg administered subcutaneously after randomization and before the first thrombectomy pass, whereas participants assigned to the control group receive guideline-recommended standard of care alone. The original target sample size was 652 participants. The protocol prespecified one sample-size re-estimation after approximately 50% of the initially planned participants had completed the 90-day primary outcome assessment. Following the prespecified re-estimation, the independent Data and Safety Monitoring Board recommended at its third meeting on August 3, 2026 that the total sample size be increased by 50%, from 652 to 978 participants, in accordance with the predefined adaptive rules. No unblinded treatment results were disclosed to the investigators or other members of the blinded study team. The current target sample size is therefore 978 participants. The primary outcome is favorable functional outcome at 90 ± 7 days, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary efficacy outcomes include the ordinal distribution of mRS scores, National Institutes of Health Stroke Scale (NIHSS) score and change from baseline, low-density lipoprotein cholesterol (LDL-C) goal attainment and change from baseline, changes in inflammatory markers, severe disability, all-cause mortality, recurrent ischemic stroke, new hemorrhagic stroke, major adverse cardiovascular events, and health-related quality of life assessed using the EuroQol 5-Dimension questionnaire. Safety outcomes include symptomatic intracranial hemorrhagic transformation, serious adverse events, and adverse events of special interest. The 90-day mRS outcome is assessed centrally by an independent Outcome Assessment Committee blinded to treatment allocation.