OBJECTIVES: Various interventions such as novel oral anticoagulants and bundled anticoagulant care are available for stroke prevention in patients with atrial fibrillation (AF). However, there is an absence of simultaneous comparison of all interventions. Hence, this research compares efficacy and safety of anticoagulant interventions in AF patients.

METHODS: A network-meta analysis based on a systematic review of randomized controlled trials (RCTs) comparing anticoagulation interventions in AF patients were conducted. Several databases were searched from inception till Nov 23^rd, 2017. The primary efficacy outcomes were stroke or systemic embolism and all-cause mortality. The primary safety outcome was major bleeding. Risk of bias was performed to assess the quality of RCTs. Ranking of interventions was based on SUCRA ranking.

RESULTS: A total of 51 studies involving 103,954 AF patients were included. Compared with usual warfarin care, two bundled interventions; patient’s self-management of warfarin (RR 0.39 [95% CI 0.17-0.89]) and genotype-guided warfarin dosing in anticoagulation clinic (RR 0.24 [95% CI 0.06-0.89]) were significantly associated with a reduced risk of stroke and systemic embolism. No significant difference in mortality risk was recorded among all interventions. For major bleeding, dabigatran 110mg twice daily (RR 0.81 [95% CI 0.70-0.94]), edoxaban 30mg daily (RR 0.48 [95% CI 0.42-0.56] edoxaban 60mg daily (RR 0.80 [95% CI 0.71-0.90]) and apixaban (RR 0.70 [95% CI 0.61-0.80]) were associated with significant reductions compared to usual warfarin care. Based on SUCRA values of stroke prevention, bundled intervention of genotype-guided warfarin dosing in anticoagulation clinic were ranked the best, followed by patient’s self-management of warfarin. The global inconsistency test suggested no evidence of inconsistency of treatment effects for all outcomes.

CONCLUSIONS: Bundled anticoagulant interventions are efficacious and remain a viable option especially in low and middle-income countries. Nonetheless, trials directly comparing the benefits and harms of these interventions are required to overcome the need for indirect comparisons.