Warfarin and direct oral anticoagulants: a systematic review on non-inferiority studies in atrial fibrillation and deep venous thrombosis

New oral anticoagulants (NOACs) have become an alternative for patients receiving long-term anticoagulation in atrial fibrillation (AF) and deep vein thrombosis (DVT). Studies of non-inferiority between NOACs and warfarin are designed to demonstrate that the former maintain at least the same efficacy and better safety in hemorrhagic events than warfarin. A systematic review and meta-analysis of randomized controlled trials was conducted in atrial fibrillation (AF) and deep vein thrombosis (DVT). The primary event was stroke (ischemic stroke and systemic embolism) for AF, recurrent venous thrombosis for DVT and the safety event was major bleeding for both pathologies. In AF, the analysis showed equivalence and significant reduction of NOACs compared to warfarin, with a 24% reduction in the relative risk [RR (IC95%)=0.76 (0.69-0.84), p<0.001]. In the safety analysis, all studies did not reveal differences with warfarin and the overall result showed a non-significant risk reduction of 14% [RR (IC95%)=0.86 (0.76-1.01), p=0.058]. For DVT, all studies showed non-inferiority criteria in comparison with warfarin [RR (IC95%) = 0.93 (0.79-1.08), p=0,372]. The safety analysis indicated superiority of NOACs over warfarin in all studies. The combined result revealed that there was a significant reduction of the risk of bleeding (42%) in favor of NOACs compared to warfarin [RR (IC95%) = 0.58 (0.42-0.79), p<0.0001]. In conclusion, these results showed that NOACs are a good alternative for therapeutic use in AF and DVT, with similar efficacy on warfarin but with a slight advantage in the reduction of hemorrhagic risk.