Real-World Direct Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Medicare Beneficiaries With Atrial Fibrillation.

It remains unknown whether the comparative effectiveness of direct oral anticoagulants (DOACs) and warfarin differs between atrial fibrillation patients with and without a history of stroke or transient ischemic attack (TIA). Using 2012 to 2014 Medicare claims data, we identified patients newly diagnosed with AF in 2013 to 2014 who initiated apixaban, dabigatran, rivaroxaban, or warfarin. We categorized patients based on a history of stroke or TIA. We constructed Cox proportional hazard models that included indicator variables for treatment groups, a history of stroke or TIA, and the interaction between them, and controlled for demographics and clinical characteristics. DOACs were generally more effective than warfarin in stroke prevention; however, there were important differences between subgroups defined by a history of ischemic stroke. In particular, the superiority of dabigatran compared with warfarin in ischemic stroke prevention was more pronounced in patients with a history of stroke or TIA (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48 to 0.85) than in patients with no history of stroke or TIA (HR 0.94; 95% CI 0.75 to 1.16; p value for interaction = 0.034). There was no difference in the risk of stroke between apixaban, dabigatran, and rivaroxaban in patients with no history of stroke or TIA. However, in patients with a history of stroke or TIA, the risk of stroke was lower with dabigatran (HR 0.64; 95% CI 0.48 to 0.85) and rivaroxaban (HR 0.70; 95% CI 0.56 to 0.87), compared with apixaban (p value for both interactions <0.05). In conclusion, the comparative effectiveness of DOACs differs substantially between patients with and without a history of stroke or TIA; specifically, apixaban is less effective in patients with a history of stroke or TIA.