Net clinical benefit of direct oral anticoagulants in very elderly and high bleeding risk patients with atrial fibrillation who are often excluded from oral anticoagulation therapy: a nationwide popul

Abstract

Abstract Background In the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial, low-dose edoxaban (15mg once daily) showed better efficacy for stroke prevention and positive net clinical benefit compared to placebo in very elderly and high bleeding risk patients with atrial fibrillation (AF) who often excluded from oral anticoagulation (OAC) therapy. However, there are limited data to generalize the ELDERCARE-AF results into daily practice. Purpose To investigate the optimal OAC strategy for the best net clinical benefit in ELDERCARE-AF-like patients. Methods Using the Korean nationwide claims database, we included patients with incident non-valvular AF aged 80 years or older between 2014 and 2017. Among these, patients with one or more of the following criteria were finally included in the analysis: a low creatinine clearance (15 to 30 mL/min), a history of bleeding from a critical area or organ or gastrointestinal bleeding, low body weight (≤45kg), continuous use of nonsteroidal anti-inflammatory drugs, or current use of an antiplatelet drug. The risks of ischemic stroke, major bleeding, all-cause death, and composite clinical outcome (ischemic stroke+major bleeding+all-cause death) as a measure of net clinical outcome were evaluated during follow-up. The inverse probability of treatment weighting (IPTW) method was used to balance covariates between the groups. Results A total of 23,858 patients were finally included (no OAC, n=16,575; warfarin, n=2390; and direct oral anticoagulants (DOACs), n=4893, respectively). Among DOAC group, 69% used low-dose including rivaroxaban 15 mg once daily, dabigatran 110 mg twice daily, apixaban 2.5 mg twice daily, and edoxaban 30 mg once daily and 9% used very low dose including rivaroxaban 10 mg once daily and edoxaban 15 mg once daily (Figure). Median follow-up duration was 2 years (interquartile ranges, 1 to 3 years). Baseline characteristics were well-balanced after IPTW. Compared to the no OAC group, the DOAC group was associated with a lower risk of ischemic stroke (hazard ratio [HR], 95% confidence interval [CI]: 0.81, 0.68–0.95) and all-cause death (0.90, 0.85–0.95), and a higher risk of major bleeding (1.43, 1.20–1.69) (Figure). Patients treated with DOAC showed a lower risk of composite clinical outcome compared to those without OAC treatment (0.93, 0.88–0.98). Warfarin treatment did not reduce the risk of ischemic stroke (1.03, 0.85–1.23) and all-cause death (1.05, 0.99–1.12), but increased the risk of major bleeding (1.60, 1.32–1.92) and the composite clinical outcome (1.08, 1.02–1.15) compared to no OAC group. Conclusion In very elderly patients with non-valvular AF who had one or more frail components, DOACs which were currently prescribed in usual clinical practice showed better effectiveness and positive net clinical benefit compared to no OAC treatment. Compared to the latter, warfarin did not show benefit and possible harm. Funding Acknowledgement Type of funding sources: None.