Clinical outcomes according to dose reduction criteria of apixaban in Japanese elderly patients with atrial fibrillation: J-ELD AF Registry subanalysis

Dose reduction of apixaban is applied in atrial fibrillation (AF) patients fulfilling ≥ 2 of the following criteria: (1) age ≥ 80 years, (2) body weight ≤ 60 kg and (3) serum creatinine ≥ 1.5 mg/dL. However, the clinical significance of each criterion remains unclear. The J-ELD AF Registry is a prospective observational study of elderly (≥ 75 years) Japanese AF patients receiving on-label dose of apixaban. In patients receiving the standard dose (5 mg bid, n = 1243), the incidence rates (% per patient-year) of stroke or systemic embolism in those fulfilling none [n = 516] or one of the above criteria (1) [n = 328], (2) [n = 378] and (3) [n = 21] were 1.24, 2.32, 1.41 and 4.93 (log-rank P = 0.422), respectively, and those of bleeding requiring hospitalization were 1.03, 0.99, 1.98 and 4.93 (P = 0.318), respectively. In patients receiving a reduced dose (2.5 mg bid, n = 1,515), the incidences of stroke or systemic embolism in those fulfilling (1)/(2) [n = 1,331], (1)/(3) [n = 65], (2)/(3) [n = 23] and all three criteria [n = 96] were 1.38, 1.64, 4.67 and 3.51 (P = 0.295), respectively, and those of bleeding requiring hospitalization were 2.04, 1.64, 0.00 and 4.71 (P = 0.318), respectively. Univariate analysis demonstrated that the types or combinations of each criterion was not significantly associated with the incidence of thromboembolic or bleeding events. The types or combinations of the three apixaban dose reduction criteria did not have significant impact on effectiveness and safety in Japanese elderly AF patients receiving on-label dose of apixaban, although the impact of the creatinine criterion remains uncertain due to the few number of the patients.