The efficacy and safety of on-label reduced-dose apixaban in patients with atrial fibrillation in real-world practice

Background/Aims: In pivotal randomized trials, only a small proportion of patients received the reduced apixaban dose, limiting the generalizability of those findings. We evaluated the efficacy and safety of on-label reduced-dose apixaban in Korean patients with atrial fibrillation (AF).Methods: Patients with non-valvular AF meeting on-label criteria for reduced-dose apixaban (2.5 mg twice daily) were enrolled. Eligible patients fulfilled at least two criteria: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL. The primary efficacy outcome was stroke or systemic embolism; primary safety outcome was major bleeding. The secondary composite outcome included myocardial infarction, heart failure hospitalization, cardiac intervention, and all-cause mortality.Results: A total of 1,655 patients were enrolled (mean age 82.8 ± 4.4 yr; 60.5% female). During 1,467.6 patient-years of follow-up, stroke or systemic embolism occurred at 1.64 per 100 patient-years and major bleeding at 3.00 per 100 patient-years. In multivariate analysis, prior stroke/TIA (HR 2.59, p = 0.034), congestive heart failure (CHF) (HR 2.31, p = 0.041), and diabetes mellitus (DM) (HR 2.26, p = 0.047) were significant independent predictors of stroke/systemic embolism. For major bleeding, CHF (HR 2.48, p = 0.003) and severe renal impairment (eGFR 15–29 mL/min/1.73 m2; HR 3.33, p = 0.007) were significant predictors. The secondary composite outcome was independently associated with older age, CHF, DM, and graded renal impairment.Conclusions: The INSPIRE study provides real-world evidence supporting guideline-directed reduced-dose apixaban in Asian populations, while identifying high-risk subgroups requiring careful patient selection and individualized management strategies.