Comparative safety and effectiveness of direct oral anticoagulants and warfarin in patients with venous thromboembolism in Finland, Norway and Sweden

<b>Aim:</b> Clinical trial data have demonstrated that direct oral anticoagulants (DOACs) are both noninferior to and safer than conventional therapy for the treatment of venous thromboembolism (VTE). This study aimed to compare the effectiveness and safety of DOACs versus warfarin using Nordic population-based registries. <b>Materials & methods:</b> This observational cohort study used Swedish, Norwegian and Finnish national administrative data from 2012 to 2018. We identified treatment-naive adult patients with noncancer-related VTE treated with either a DOAC (apixaban or rivaroxaban) or warfarin. We employed inverse probability of treatment weighting for each DOAC-warfarin comparison and assessed the risks of bleeding (overall and by site: gastrointestinal bleeding [GI], intracranial bleeding [ICH], or other bleeding) and recurrent VTE within 6 months after treatment initiation. Cox proportional hazards models estimated the adjusted hazard ratios of each end point. Country estimates were combined using meta-analyses. <b>Results:</b> After inverse probability of treatment weighting, 22,450 warfarin, 14,542 apixaban and 23,002 rivaroxaban patients were included. At 6 months, for apixaban versus warfarin, the risk of bleeding was lower overall (hazard ratio: 0.51 [95% CI: 0.43, 0.61]) and by site (GI: 0.65 [0.45, 0.93]; ICH: 0.58 [0.34, 0.97]; other: 0.45 [0.34, 0.58]). For recurrent VTE the risk was similar for apixaban versus warfarin (0.85 [0.71, 1.02]). For rivaroxaban versus warfarin the risk of bleeding was lower for overall and other bleeding (0.86 [0.75, 0.99]; 0.81 [0.69, 0.95], respectively), but similar for GI and ICH bleeding (1.06 [0.84, 1.34]; 0.68 [0.47, 1.00], respectively). For recurrent VTE the risk was lower for rivaroxaban versus warfarin (0.74 [0.63, 0.87]). <b>Conclusion:</b> DOACs showed improved safety and at least similar effectiveness compared with warfarin, which is in line with clinical trial estimates.