Real-world direct comparison of the effectiveness and safety of apixaban, dabigatran, rivaroxaban, and warfarin in medicare beneficiaries with atrial fibrillation: a subgroup analysis by a history of ischemic stroke or transient ischemic attack

No studies have directly compared the effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin among patients with and without history of ischemic stroke and transient ischemic attack (TIA) using Medicare data. This is important since patients with atrial fibrillation (AF) and previous ischemic stroke or TIA have a particularly high risk of stroke. Using 2012-2014 Medicare Part D data, we identified patients newly diagnosed with AF in 2013-2014 who initiated apixaban (n=2358), dabigatran (n=1415), rivaroxaban (n=5139), or warfarin (n=12,352). We categorized them according to history of stroke or TIA. Primary outcomes included ischemic stroke as a measure of effectiveness and bleeding as a measure of safety. We constructed Cox proportional hazard models including indicator variables for treatment, a history of stroke or TIA, and the interaction between treatment and clinical history, adjusted for demographics and clinical characteristics. DOACs were more effective than warfarin for stroke prevention overall; however, the superiority of dabigatran was more pronounced in patients with a history of stroke or TIA: the hazard ratio (HR) for ischemic stroke with dabigatran compared to warfarin was 0.64(95%CI 0.48-0.85) for patients with a history of stroke or TIA, and was 0.94 (95%CI 0.75-1.16) for patients with no history of stroke or TIA (interaction p-value =0.034). Although there was no difference in the risk of stroke between apixaban and dabigatran (HR 0.94; 95%CI 0.71-1.24) or between apixaban and rivaroxaban (HR 1.01; 95%CI, 0.81-1.27) for patients with no history of stroke or TIA, the risk of ischemic stroke was lower with dabigatran (HR 0.61;95%CI 0.44-0.85) and with rivaroxaban (HR 0.70; 95%CI 0.56-0.87) in patients with a history of stroke or TIA compared to apixaban (both interaction p-values<0.05). The comparative safety of DOACs and warfarin did not differ between patients with and without a history of stroke or TIA. 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. Our results reinforce the need to tailor anticoagulation to AF patient characteristics regarding the public health significance of stroke prevention.