Antiplatelet regimens after ischemic stroke or transient ischemic attack: a systematic review and updated network meta-analysis

Background: It is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic ischemic stroke, and it is necessary to choose the optimal regimen according to the clinical situation. Methods: We utilized 3 databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials to find randomized controlled trials that met our criteria, and performed network meta-analyses in recurrent stroke, composite outcomes, major bleeding events, recurrent ischemic stroke, and all bleeding events. Three-dimensional clustered rank plots were used to obtain the net clinical benefit. Subgroup analyses were performed according to the symptom-onset-to-treatment time (<72 and >72 h), stroke subtypes (large artery atherosclerosis and small vessel occlusion), and dual antiplatelet agent treatment duration. Results: A total of 69 trials were enrolled. Cilostazol was associated with a lower risk of recurrent stroke, major bleeding events, composite outcomes, recurrent ischemic stroke, and all bleeding events compared to low to medium dose aspirin. The three-dimensional rank plot showed that cilostazol had the highest net clinical benefit. The combination of aspirin plus clopidogrel had greater efficacy in the <72 h after stroke onset and large artery atherosclerosis subgroups, and when it was restricted to1 month of use major bleeding risk was not higher than aspirin. The combination of aspirin plus dipyridamole had greater efficacy and safety comparable to aspirin in terms of small vessel occlusion. Conclusions: The efficacy and safety profiles among antiplatelet regimens may differ according to clinical situation, although cilostazol, aspirin plus clopidogrel, and aspirin plus dipyridamole may be considered as preferable options.