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

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.

Inclusion criteria

• Adults (age 18 years and older);
• Imaging diagnosis of acute ischemic stroke with anterior circulation large vessel occlusion (including: internal carotid artery, middle cerebral artery M1 and M2, anterior cerebral artery A1 and A2);
• Planned to undergo endovascular intervention within 24 hours of symptom onset (or last known well time) according to local guidelines;
• Provision of informed consent by the patient or his/her legally authorized representative (or by an appropriate agent according to local requirements).

Exclusion criteria

• ASPECTS score ≤5 on cranial CT imaging;
• Pre-existing functional impairment, with mRS score >2;
• Patients who are allergic to PCSK9 inhibitors;
• Patients who have received PCSK9 monoclonal antibody within 1 month prior to enrollment or PCSK9 siRNA therapy within 6 months prior to enrollment;
• Severe renal insufficiency, defined as estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m2 at final screening;
• Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal;
• Severe, concomitant non-cardiovascular disease expected to reduce life expectancy to less than 3 months;
• Pregnant or lactating women;
• Patients who are participating in other clinical trials;
• Other conditions deemed unsuitable for inclusion in the clinical study by the investigator.