Direct Comparative Efficacy And Safety Of Novel Oral Anticoagulants In Patients With Atrial Fibrillation:A Systematic Review And Meta-analysis

Objective: New oral anticoagulants are effective and convenient in the prevention and treatment of venous thrombosis and stroke in patients with non-valvular atrial fibrillation.What's more,numerous studies have demonstrated their advantages over warfarin in the prevention of embolism.It also has a lower risk of bleeding.However,there is limited data about the comparison of the new oral anticoagulants.In the absence of large randomized controlled trials with direct comparison between the new oral anticoagulants,the aim of this study is to directly compare the effectiveness and safety of new oral anticoagulants in patients with non-valvular atrial fibrillation by meta-analysis.It's expected to provide valuable information for clinical decision making.Method: We search from PubMed,EMBASE and Cochrane Web sites for the studies.Studies need to be published from 2009 to 2018 and compare directly the effectiveness and safety of anticoagulation in patients with non-valvular atrial fibrillation between Abelian group,Rivaroxaban and Apixaban.Two evaluators selected the data according to the inclusion criteria and exclusion criteria.And then they evaluated the bias risk of the data.The evaluators input the data into Stata14 software and analyzed the stroke,systemic embolism and massive hemorrhage.All the data involved were dichotomous.And evaluators used the Hazard Ratio(HR)as the effect indicator and the Confidence Interval(CI)as the interval estimate.Results: Among all of those papers,10 were included in this study.As to the comparison between Rivaroxaban and Dabigatran,a total of eight studies were included in the prevention of stroke or systemic embolism.The result showed that there was no significant decrease in the incidence of stroke or systemic embolism(HR =1.01,95% CI=0.90-1.13,p=0.884).In the case of major bleeding,eight articles were included and the result showed that Rivaroxaban increased the risk of major bleeding significantly(HR=1.37,95% CI=1.25-1.50,p=0.001).As to the comparison between Apixaban and Dabigatran,four papers were included in the prevention of stroke or systemic embolism.The result showed that there was no significant reduction in the incidence of stroke or systemic embolism(HR=1.04,95% CI=0.83-1.30,p=0.751).In the case of major bleeding,five articles were included in the study and the result showed that Apixaban could effectively reduce the risk of massive hemorrhage(HR=0.78,95% CI=0.61-0.98,p=0.032).As to the comparison between Apixaban and Rivaroxaban,four papers were included in the prevention of stroke or systemic embolism.The result showed that there was no significant reduction in the incidence of stroke or systemic embolism(HR=0.98,95% CI=0.78-1.23,p=0.888).A total of five articles on major bleeding were included and the result showed that Apixaban effectively reduced the risk of massive bleeding(HR=0.55,95% CI=0.41-0.73,p<0.001).Compared with Abelian group and Rivaroxaban,Apixaban had the best safety and the lowest risk of bleeding.However,no significant difference was observed in the prevention of stroke or systemic embolism between Dabigatran,Rivaroxaban and Apixaban.Conclusion: Direct comparison of new oral anticoagulants has no significant difference in the effectiveness of anticoagulation therapy for atrial fibrillation.But there are differences in the safety.Compared with Dabigatran and Rivaroxaban,Apixaban had the best safety and the lowest risk of bleeding.However,no significant difference was observed in the prevention of stroke or systemic embolism between Dabigatran,Rivaroxaban and Apixaban.This may provide some help for clinicians to choose which NOACs to use.But this needs to be further confirmed by direct comparison of the new oral anticoagulants with larger randomized controlled trials.