Early and Long-Term Outcomes After DOAC Initiation in Hospitalized Patients With Newly Diagnosed Atrial Fibrillation.

New-onset atrial fibrillation (AF) is common among acutely hospitalized patients and is associated with increased risks of stroke and mortality. However, anticoagulation in this setting involves a temporal tradeoff between early bleeding during recovery and potential long-term stroke prevention, and data guiding direct oral anticoagulant (DOAC) initiation at discharge remain limited. We conducted a retrospective cohort study of adults with newly diagnosed AF identified between 3 days before hospital admission and hospital discharge within the Baylor Scott & White Health system (July 2020 to June 2024), comparing patients initiated on DOAC therapy at discharge with those who were not. Outcomes included major adverse cardiovascular events (MACE: all-cause death, nonfatal myocardial infarction, or ischemic stroke/transient ischemic attack) and net adverse clinical events (NACE: MACE or major bleeding) at 30 days and 3 years. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), and landmark cumulative incidence analyses assessed temporal trends after discharge. Among 16,641 patients (mean age 75.1 years; 41.8% women), 7,181 (43.2%) were discharged on a DOAC. In adjusted analyses, DOAC use was associated with lower risk of 3-year MACE (HR 0.61, 95% CI 0.58 to 0.65, p < 0.001) and NACE (HR 0.64, 95% CI 0.61 to 0.68, p < 0.001) compared with those not receiving DOAC therapy. Landmark analyses showed consistent reductions in MACE at both 30 days (HR 0.61, 95% CI 0.57 to 0.65) and 3 years (HR 0.68, 95% CI 0.62 to 0.74). Patients treated with DOACs had a lower risk of NACE at both 30 days (HR 0.65, 95% CI 0.61 to 0.69) and 3 years (HR 0.67, 95% CI 0.62 to 0.73). Overall, DOAC initiation at discharge in patients with newly diagnosed AF identified between 3 days before hospital admission and hospital discharge was associated with lower early and long-term ischemic risk, with lower rates of both MACE and NACE observed at 30 days and 3 years, underscoring the need for individualized decision-making regarding anticoagulation during acute hospitalization.