Abstract
BACKGROUND: Whether or not to reinitiate direct oral anticoagulants (DOACs) in atrial fibrillation patients who survived an antithrombotic agent-associated intracranial hemorrhage (ICH) event remains inconclusive. OBJECTIVES: The primary purpose of this study was to investigate the effectiveness and safety of DOACs after ICH, with the secondary objective to explore the optimal timing of DOAC reinitiation. METHODS: A sequential target trial emulation study was conducted using the National Health Insurance claims data in Taiwan. We included AF patients receiving antithrombotic therapy who later developed an ICH event between June 2012 and December 2018. Post-ICH DOAC reinitiation status was assessed at 6 consecutive 14-day intervals after discharge. We further stratified our analysis using the stroke severity index to explore the optimal timing of DOAC reinitiation. Study outcomes were all-cause mortality, ICH, and ischemic stroke. Adjusted HRs (aHRs) were estimated using Cox proportional hazards models. RESULTS: DOAC reinitiation was associated with lower risks of all-cause mortality (aHR: 0.73; 95% CI: 0.61-0.88) without increased ICH risk (aHR: 1.21; 95% CI: 0.81-1.80) compared with no antithrombotic therapy after ICH. The ischemic stroke risk after reinitiating DOAC was similar to that with no antithrombotic therapy (aHR: 0.73; 95% CI: 0.47-1.14). Reinitiating DOACs within 14 and 28 days after discharge most benefited patients with low and high ICH severity, respectively. CONCLUSIONS: DOAC is associated with lower risk of all-cause mortality. The optimal timing of DOAC reinitiation varies by ICH severity, with later reinitiation recommended for patients with higher ICH severity.