Stroke prevention with direct oral anticoagulants in high-risk elderly atrial fibrillation patients at increased bleeding risk

Aims Elderly atrial fibrillation (AF) patients with risk factors of bleeding are often considered ineligible for standard oral anticoagulants (OACs). The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF) trial recently showed that edoxaban 15 mg/day was superior to placebo for preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding. Our aim was to investigate a real-world cohort of AF patients similar to the ELDERCARE-AF cohort, with regard to the impact of direct oral anticoagulant (DOAC) use compared to non-OAC use, in relation to clinical outcomes. Methods and results From 1 January 2012 to 31 December 2016, 15 183 AF patients aged >= 80 years (mean age 86.63 years [SD 4.79]; 48.7% male) with a congestive heart failure, hypertension, age >= 75 years, diabetes mellitus, and prior stroke or transient ischemic attack (CHADS(2)) score >= 2 who met the enrolment criteria (generally similar to ELDERCARE-AF) were identified from the Taiwan National Health Insurance Research Database. Patients were categorized into two groups according to their stroke prevention strategies, i.e. without OACs (n = 9084) and DOACs (n = 6099). Patients receiving DOACs were further stratified into reduced-dose- or full-dose-regimen groups. Compared with the non-OAC group as a reference, DOAC use (whether at reduced dose or full dose) was associated with a lower risk of ischaemic stroke (adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.67-0.88) and all-cause mortality (aHR 0.39, 95% CI 0.37-0.42), while the risks of intracranial haemorrhage and major bleeding were similar. The risks of composite outcomes of 'ischaemic stroke or mortality' (aHR 0.42, 95% CI 0.40-0.45) and 'ischaemic stroke or major bleeding or mortality' (aHR 0.49, 95% CI 0.46-0.52) were significantly lower with DOAC use. When compared with the non-OAC group as the reference group, DOACs (whether reduced dose or full dose) showed a positive net clinical benefit. The results were generally consistent even after propensity matching. Conclusion In routine clinical care, DOACs (whether reduced or full dose) were associated with a lower risk of ischaemic stroke, mortality, and the composite endpoint, when compared with non-OAC use in high-risk elderly AF patients at increased bleeding risk. Our findings provide complementary 'real-world' data to support the generalizability of the results of the ELDERCARE-AF trial to other DOACs in daily clinical practice.