P4782Direct comparison of dabigatran, apixaban, rivaroxaban and edoxaban for effectiveness and safety among patients with non-valvular atrial fibrillation

Abstract

Abstract Background Although the prescription of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been rapidly increasing in Asian countries since their introduction, limited evidence exists on the effectiveness and safety of warfarin and all 4 available NOACs from current clinical practice in the Asian population. We aimed to evaluate comparative effectiveness and safety of warfarin and all 4 available NOACs Methods We studied a retrospective observational cohort of oral anticoagulant (OAC) naïve non-valvular AF patients treated with warfarin or NOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) from January 2015 to December 2017, based on the Korean Health Insurance Review and Assessment database. For the comparisons, warfarin to 4 NOACs and NOAC to NOAC comparison cohorts were balanced using inverse probability of treatment weighting (IPTW). Ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), major bleeding (MB) and a composite clinical outcome were evaluated. Results A total of 116,804 patients were included (25,420 with warfarin, 35,965 with rivaroxaban, 17,745 with dabigatran, 22,177 with apixaban, and 15,496 with edoxaban). Patients treated with warfarin were younger (mean age 67 years) compared to NOAC users (71 to 73 years) and had lower mean CHA2DS2-VASc score (3.18) than the NOAC groups (3.58 to 3.76). Among the NOAC users, patients prescribed apixaban were older (mean age 73 years) than other NOAC groups (71 to 72 years), had higher mean CHA2DS2-VASc score (3.76) than others (3.55 to 3.63) and higher burden of comorbidities. More than half of patients were prescribed reduced dose regimes. After IPTW, all baseline covariates were well balanced across 5 treatment groups. Compared with warfarin, all NOACs were associated with lower risks of ischemic stroke, ICH, GIB, MB and composite outcome (Figure A). Apixaban and edoxaban showed a lower rate of ischemic stroke compared with rivaroxaban and dabigatran (Figure B). Apixaban, dabigatran and edoxaban had a lower rate of GIB and MB compared with rivaroxaban. The composite clinical outcome was non-significantly different for apixaban vs edoxaban. Conclusions In this large contemporary observational Asian cohort, all 4 NOACs were associated with lower rates of ischemic stroke and major bleeding compared to warfarin. Differences in clinical outcomes between NOACs may give useful guidance for physicians to choose drugs to fit their particular patient clinical profile.