The effectiveness and safety of low-dose rivaroxaban in Asians with non-valvular atrial fibrillation

Background: Rivaroxaban (20 mg/15 mg once daily) is an effective and safe alternative to warfarin for stroke prevention in patients with non-valvular AF (NVAF). Low-dose rivaroxaban (15 mg/10 mg once daily) has been only approved for NVAF patients in Japan and Taiwan, although its effectiveness and safety at low doses remain unclear among Asians with NVAF. The objective of the study is to compare the effectiveness and safety of low-dose rivaroxaban to those of warfarin among Asians with NVAF. Methods: This dynamic cohort study used data from the Taiwan National Health Insurance Database (NHIRD) to enroll 14,971 patients taking 15 mg rivaroxaban, 11,029 patients taking 10 mg rivaroxaban, and 16,000 NVAF patients taking warfarin. Inverse probability of weighting using propensity scores was used to balance covariates across study groups. Results: The adjusted hazard ratio [95% confidence interval] comparing rivaroxaban 15 and 10 mg with warfarin (reference) was as follows: ischemic stroke/systemic embolism, 0.84 [0.74–0.96; P = 0.0080], and 0.84 [0.73–0.96; P = 0.0097]; myocardial infarction, 0.53 [0.37–0.74; P = 0.0002], and 0.88 [0.65–1.19; P = 0.3910]; intracranial hemorrhage, 0.44 [0.34–0.55; P < 0.0001], and 0.53 [0.42–0.66; P < 0.0001]; major gastrointestinal bleeding, 0.82 [0.67–0.99; P = 0.0387], and 0.58 [0.47–0.72; P < 0.0001]; all hospitalized major bleeding, 0.63 [0.55–0.73; P < 0.0001], and 0.56 [0.48–0.65; P < 0.0001]; and all-cause mortality, 0.55 [0.51–0.60; P < 0.0001], and 0.58 [0.53–0.63; P < 0.0001]. Conclusions: Both low doses of rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism, intracranial hemorrhage, gastrointestinal bleeding, all major bleeding, and all-cause mortality compared with warfarin in Asian NVAF patients. The 15 mg rivaroxaban dose was associated with a lower risk of acute myocardial infarction compared to warfarin.