Background & Purpose: There are no randomized clinical trial (RCT) data regarding direct comparisons between different novel oral anticoagulants (NOACs). We conducted a network meta-analysis using published data from secondary prevention subgroups of different phase III RCTs comparing individual NOACs to warfarin.
Methods: We performed a comprehensive literature search in Medline, SCOPUS and the Cochrane Central Register of Controlled Trials to identify available RCTs. The primary efficacy outcome was stroke or systemic embolism and the primary safety outcome was the occurrence of a major bleeding event during the follow-up period. We performed a Bayesian-framework, multiple-treatments meta-analysis and ranked the comparative effects of all NOACs against warfarin with the surface under the cumulative ranking (SUCRA) probabilities.
Results: We identified 4 RCTs (including 15,302 patients) comparing individual NOACs (Apixaban, Dabigatran, Rivaroxaban) to warfarin. In indirect comparison analysis Dabigatran was related to a significantly lower risk of hemorrhagic stroke compared to Rivaroxaban (RR=0.28; 95%CI: 0.11-0.75), while Rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared to Dabigatran (RR=0.14; 95%CI: 0.03-0.74). Clustered ranking plot for the primary efficacy and safety endpoints highlighted Apixaban as the treatment with the probably best benefit-to-risk ratio profile among NOACs followed by Dabigatran and Rivaroxaban (Figure).
Conclusion: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention. These findings serve only for hypothesis generation and require independent confirmation in head to head RCTs.
Figure legend: Corresponding SUCRA Probabilities for different NOACs to be ranked as the most effective treatment for the prevention of Stroke/systemic embolism (y axis) and Major bleeding (x axis)