Clinical risk factors of stroke and major bleeding in patients with non-valvular atrial fibrillation under rivaroxaban: the EXPAND Study sub-analysis

For Japanese patients with non-valvular atrial fibrillation (NVAF), the risk of stroke and major bleeding events was assessed by using the CHADS_2, CHA₂DS₂-VASc, and HAS-BLED scores. The risk factors for embolism and major bleeding under DOAC may be different from current reports. We analyzed the data set of the EXPAND Study to determine the risk factors for events among Japanese NVAF patients in the era of direct oral anticoagulant. Using the data of EXPAND Study, the validity for predictability of the CHADS₂, CHA₂DS₂-VASc, and HAS-BLED scores was identified using the receiver operating characteristic curve analysis. Multivariate analysis was performed with the Cox proportional hazard model to determine the independent risk factors for stroke/systemic embolism and major bleeding among NVAF patients receiving rivaroxaban. Explanatory variables were selected based on the univariate analysis. A total of 7141 patients (mean age 71.6 ± 9.4 years, women 32.3%, and rivaroxaban 15 mg per day 56.5%) were included. Incidence rates of stroke/systemic embolism and major bleeding were 1.0%/year and 1.2%/year, respectively. The multivariate analysis revealed that only history of stroke was associated with stroke/systemic embolism (hazard ratio 3.4, 95% confidence interval 2.5-4.7, p < 0.0001). By contrast, age (1.7, 1.1–2.6, p = 0.0263), creatinine clearance (CrCl) 30–49 mL/min (1.6, 1.2-2.2, p = 0.0011), liver dysfunction (1.7, 1.1–2.8, p = 0.0320), history/disposition of bleeding (1.8, 1.0–3.0, p = 0.0348), and concomitant use of antiplatelet agents (1.6, 1.2–2.3, p = 0.0030) were associated with major bleeding. This sub-analysis showed that some components of the HAS-BLED score were independently associated with major bleeding in Japanese NVAF patients receiving anticoagulation therapy by rivaroxaban. Additionally, CrCl value of 30–49 mL/min was an independent predictor of major bleeding in patients receiving rivaroxaban.