The impact of concomitant use of rosuvastatin or atorvastatin plus clopidogrel on the platelet inhibition and clinical outcomes in acute large-vessel minor stroke or TIA: A randomized controlled multi-center trial, the ROCATIS-1 trial

Background Although clopidogrel is commonly used for ischemic stroke secondary prevention, 20–50% of patients experienced clopidogrel failure and recurrence of ischemic events. Objectives We aimed to evaluate the benefits or hazards of adding atorvastatin or rosuvastatin to clopidogrel on the clopidogrel-induced inhibition of platelet activation and vascular events prevention. Design Our multi-center, randomized, single-blinded, parallel-group trial was conducted between 10th April 2024 and 10th May 2026. Methods 600 first-ever, large-vessel minor ischemic stroke or TIA patients received 40 mg of atorvastatin or 20 mg of rosuvastatin during the first 24 hours of stroke onset once daily till the 90th day after stroke onset. Both groups received open-label 300 mg loading doses of aspirin and clopidogrel during the first 24 hours after stroke onset, followed by 75 mg clopidogrel and 100 mg aspirin once daily for 3 weeks, then 75 mg clopidogrel only until the end of the follow-up period. We followed up with our patients for 3 months. Results The change in the percentage of platelet maximum aggregation at 3 months of treatment compared with baseline while using adenosine diphosphate ( ADP), 5 µM/L as an agonist was 54.4 (51.0-57.1) in the rosuvastatin group compared with 49.2 (45.5-52.3) in the atorvastatin group with P-value 0.003. 22 (7.3%) patients in the rosuvastatin group and 40 (13.3%) patients in the atorvastatin group experienced a composite of a new stroke, MI, or death due to vascular insults (HR 0.52; 95% CI, 0.33-0.81; P-value= 0.004), moreover, 12 (4.0%) patients in the rosuvastatin group and 19 (6.3%) in the atorvastatin group experienced recurrent stroke either ischemic or hemorrhagic, with (HR 0.60; 95% CI, 0.32-1.10; P-value 0.10). Conclusion Compared with combining atorvastatin with clopidogrel in African large-vessel minor stroke or TIA, combining rosuvastatin with clopidogrel yielded higher rates of clopidogrel-induced platelet aggregation inhibition, significantly lower rates of a composite of recurrent stroke, MI, and death due to vascular events at three months. There were no significant differences between rosuvastatin and atorvastatin regarding drug-related side effects. Our findings are hypothesis-generating and require confirmation in a double-blinded, multinational randomized trial before they can inform practice.