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All pivotal trials have evaluated non-vitamin K oral antagonists (NOACs) against warfarin. However, in some regions of the world, phenprocoumon is the most widely used vitamin K antagonist (VKA). There is little evidence documenting effectiveness and safety of NOACs compared with phenprocoumon in atrial fibrillation (AF). A retrospective cohort study using a German claims database was conducted to assess effectiveness (stroke, systemic embolism [SE]) and safety (bleeding leading to hospitalization) during therapy with NOACs and phenprocoumon in 61,205 AF patients. Hazard ratios (HRs) for effectiveness and safety outcomes were derived from Cox proportional hazard models, adjusting for baseline characteristics. Propensity score matching was performed as a sensitivity analysis. As a prespecified subgroup analysis, the effects of reduced NOAC dosing were compared with phenprocoumon. A total of 61,205 patients were identified in whom phenprocoumon ( n  = 23,823, 38.9%), apixaban ( n  = 10,117, 16.5%), dabigatran ( n  = 5,122, 8.4%), or rivaroxaban ( n  = 22,143, 36.2%) was initiated. After adjusting for baseline confounders, all three NOACs tested had significantly lower risks of stroke/SE compared with phenprocoumon (apixaban-HR: 0.77, 95% CI: 0.66-0.90; dabigatran-HR: 0.74, 95% CI: 0.60-0.91; rivaroxaban-HR: 0.86, 95% CI: 0.76-0.97). Apixaban (HR: 0.58, 95% CI: 0.49-0.69) and dabigatran (HR: 0.64, 95% CI: 0.50-0.80) were associated with lower bleeding risks than phenprocoumon, whereas the risk was similar for rivaroxaban and phenprocoumon. All three NOACs showed reduced risk of intracranial bleeding compared with phenprocoumon. Reduced doses of NOACs were predominantly used in patients with advanced age and comorbidities with generally similar effectiveness and safety benefits compared with phenprocumon as standard-dose NOACs., Competing Interests: Professor Hohnloser has served as a consultant for Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo and Jansen. Professor Nabauer has received lecture fees from Bayer, BMS/Pfizer, Boehringer Ingelheim and Daiichi Sankyo. Dr. Hohmann has served as a consultant for Pfizer and received grants from Orion Pharma. Dr. Basic is employee of Pfizer Deutschland GmbH. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Schattauer GmbH Stuttgart.)

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective and safe as vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). All pivotal trials have compared NOACs to warfarin. However, other VKAs are commonly used, for instance phenprocoumon., Patients and Methods: A retrospective cohort study using a German claims database assessed the comparative risks of bleeding leading to hospitalization during therapy with NOACs and phenprocoumon in AF patients. Endpoints consisted of major bleeding, gastrointestinal bleeding, and any bleeding. Data were collected from January 1, 2013 to March 31, 2015. Patients newly initiated on dabigatran, apixaban, rivaroxaban, or phenprocoumon were included. Hazard Ratios for bleeding events were derived from Cox proportional hazard models, adjusting for differences in baseline characteristics. Propensity score matching was performed as a sensitivity analysis., Results: A total of 35,013 patients were identified, including 3138 on dabigatran, 3633 on apixaban, 12,063 on rivaroxaban, and 16,179 on phenprocoumon. Patients prescribed apixaban or phenprocoumon were older compared to those on dabigatran or rivaroxaban and had a higher CHA 2 DS 2 -VASc score. After adjusting for baseline confounders, apixaban was associated with lower risks of major bleeding (HR 0.68, 95% CI 0.51-0.90, p = 0.008), gastrointestinal bleeding (HR 0.53, 95% CI 0.39-0.72, p < 0.001), and any bleeding (HR 0.80, 95% CI 0.70-0.92, p = 0.002) compared to phenprocoumon. There were no significant differences in bleeding risk between dabigatran and phenprocoumon. Rivaroxaban was associated with more gastrointestinal bleeding (HR 1.39, 95% CI 1.21-1.60, p < 0.001) and any bleeding (HR 1.19, 95% CI 1.10-1.28, p < 0.001). Sensitivity analysis using propensity score matching confirmed these observations., Conclusions: Apixaban therapy is associated with a significantly reduced risk of bleeding compared to phenprocoumon. Bleeding risk with dabigatran was similar to that of phenprocoumon but bleeding risk with rivaroxaban was higher.