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 (CHADS2) 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.