Antithrombotic therapy for secondary prevention in patients with stroke or transient ischemic attack: A multiple treatment network meta-analysis of randomized controlled trials

OBJECTIVE: As stroke represents one of the leading causes of mortality and disability worldwide, we aimed to determine the preventive effect of different antiplatelet therapies after an ischemic stroke or transient ischemic attack. METHODS: Network meta-analysis evaluating antiplatelet regimes after an ischemic stroke or transient ischemic attack. Searches were conducted in MEDLINE, EMBASE, and Cochrane Library databases until Nov. 23, 2021, for randomized controlled trials. Direct comparisons within trials were combined with indirect evidence from other trials by using a frequentist model. An additive network meta-analysis model was used to evaluate the influence of individual components. The primary efficacy endpoint was a recurrent stroke, the main safety outcomes were the risk of major bleeding and mortality at the longest available follow-up. RESULTS: 58 randomized controlled trials (175,730 patients) were analyzed. The analysis involved 20 antithrombotic strategies including different antiplatelet agents, combinations with aspirin, and anticoagulant therapies. Cilostazol proved to be the most efficacious in reducing stroke recurrence and the risk of bleeding (RR = 0.66, 95%CI = 0.55–0.80 and RR = 0.39, 95%CI = 0.08–2.01) compared to aspirin, respectively. Intensification with combinations of aspirin with ticagrelor or clopidogrel resulted in a lower risk of stroke recurrence (RR = 0.79, 95%CI = 0.67–0.93 and RR = 0.79, 95%CI = 0.72–0.87) but carried a higher bleeding risk (RR = 3.01, 95%CI = 1.65–5.49 and RR = 1.78 95%CI = 1.49–2.13). CONCLUSION: The prognosis of patients with an ischemic stroke or transient ischemic attack is improved with antiplatelets. Cilostazol showed the best risk-benefit characteristics without trade-off with the risk of major bleeding. Improved stroke recurrence with intensified antiplatelet regimens is counterbalanced with higher bleeding risk, and consequently, mortality remains unaffected. Treatment decisions in stroke survivals should integrate the assessment of bleeding risk for better identification of patients with the highest benefit of treatment intensification. SYSTEMATIC REVIEW REGISTRATION: Prospero registration number: CRD42020197143, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197143.