Safety and effectiveness of reduced-dose apixaban in Japanese patients with nonvalvular atrial fibrillation in clinical practice: A sub-analysis of the STANDARD study

BackgroundThe safety and effectiveness of reduced-dose apixaban 2.5 mg twice daily (BID) have not been elucidated thoroughly in Japanese patients with nonvalvular atrial fibrillation (NVAF).MethodsA post-marketing survey study included NVAF patients who newly initiated apixaban for prevention of thromboembolism, and followed them for 104 weeks. Apixaban doses were selected at the discretion of treating physicians. Hemorrhagic and thromboembolic (ischemic stroke, systemic embolism, and transient ischemic attack) events were examined. The relationship between dose reduction criteria (DRC), selected doses, and outcome events was also examined.ResultsOf 6306 patients, 3600 (57.1%) received the standard dose (5 mg BID) and 2694 (42.7%) received the reduced dose. Compared with the standard-dose group, the reduced-dose group had more female patients; the patients were older, of lower body weight, with reduced creatinine clearance, higher thromboembolic and hemorrhagic risk scores, and more frequent antiplatelet use. Incidence rates of major hemorrhage and thromboembolism were higher in the reduced-dose group compared with the standard-dose group (3.00%/year vs 1.93%/year, p = 0.001 and 1.40%/year vs 0.72%/year, p = 0.001, respectively). In the standard-dose group, 90.0% of patients did not meet the DRC (recommended standard-dose group). In the reduced-dose group, 62.4% of patients met the DRC (recommended reduced-dose group) and 34.9% did not (non-recommended reduced-dose group). Incidence rates of major hemorrhage and thromboembolism were numerically highest in the recommended reduced-dose group (3.30%/year, p = 0.007 and 1.69%/year, p < 0.001, respectively), followed by the non-recommended reduced-dose group. In multivariate analysis, apixaban dose was not associated with these outcome events.ConclusionThe reduced-dose group showed higher incidence rates of thromboembolic and major hemorrhagic events than the standard-dose group due to baseline clinical characteristics. The safety and effectiveness of reduced-dose apixaban need to be carefully monitored in clinical practice.