Long-Term Outcomes of Dose-Stratified Direct Oral Anticoagulants in Atrial Fibrillation-Results From the Alfred-AF Registry.

Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention in atrial fibrillation (AF). While reduced-dose regimens are frequently prescribed for elderly or comorbid patients, evidence on long-term safety and effectiveness remains inconsistent. We evaluated outcomes associated with dose-stratified DOAC therapy in a large, real-world AF cohort. We aimed to describe long-term all-cause mortality, stroke, and bleeding rates stratified by DOAC dose and class. We conducted a retrospective observational cohort study using a large AF registry from the Alfred Hospital. Adults with AF who were prescribed a DOAC were categorized as receiving a standard dose, a guideline-based reduced dose, or a non-guideline-based reduced dose. The primary outcomes were all-cause mortality, with secondary outcomes of major bleeding and stroke/systemic embolism rates. Cox proportional hazards models were adjusted for all significant covariates. Among 3,729 patients, 2,722 (73.0%) received standard dose, 462 (12.4%) guideline-reduced, and 547 (14.7%) non-guideline-reduced DOACs. The non-guideline-reduced dose group was associated with higher mortality compared with the full-dose DOAC group (hazard ratios [HR] 1.42, 95% CI 1.12-1.81; p <0.01), but the guideline-reduced dose group was not (HR 1.19, 95% CI 0.92-1.50; p = 0.2). Guideline-reduced dosing was associated with increased stroke/systemic embolism (HR 3.32, 95% CI 1.19-9.23; p = 0.02), while non-guideline-based dosing showed a borderline association (HR 2.22, 95% CI 0.82-5.96; p = 0.11) compared to full-dose DOAC. There was no association between major bleeding and dose groups. In conclusion, dose-adjusted DOACs were associated with a significantly higher mortality and thromboembolic risk, with no association observed between dose reduction and major bleeding. These findings suggest that dose-adjusted regimens are being selected for patients with particularly high residual risk.