RCT: Early DOACs Safe and Non-Inferior to Delayed Initiation Post-Stroke with Atrial Fibrillation
28 Oct, 2024 | 17:52h | UTCBackground: Atrial fibrillation increases ischaemic stroke risk, and patients are prone to recurrence. Prompt anticoagulation post-stroke is critical, but optimal timing is unclear due to bleeding concerns. Guidelines often delay DOAC initiation without strong evidence.
Objective: To determine if early DOAC initiation (≤4 days) is non-inferior to delayed initiation (7–14 days) in preventing recurrent ischaemic events without increasing intracranial haemorrhage risk in patients with acute ischaemic stroke and atrial fibrillation.
Methods: In this multicentre, open-label, blinded-endpoint, phase 4 randomised controlled trial at 100 UK hospitals, 3,621 adults with atrial fibrillation and acute ischaemic stroke were randomised to early or delayed DOAC initiation. Eligibility required physician uncertainty about timing. Participants and clinicians were unmasked; outcomes were adjudicated by a masked committee. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism within 90 days.
Results: Among 3,621 patients (mean age 78.5; 45% female), the primary outcome occurred in 59 patients (3.3%) in both early and delayed groups (adjusted risk difference 0.0%, 95% CI –1.1 to 1.2%). Upper confidence limit below the 2% non-inferiority margin (p=0.0003) confirmed non-inferiority. Symptomatic intracranial haemorrhage rates were similar (0.6% early vs 0.7% delayed; p=0.78). No significant differences in mortality or heterogeneity across subgroups.
Conclusions: Early DOAC initiation within 4 days is non-inferior to delayed initiation in preventing recurrent events without increasing intracranial haemorrhage risk. Findings challenge guidelines advising delayed anticoagulation and support early initiation regardless of stroke severity.
Implications for Practice: Clinicians should consider starting DOACs within 4 days post-stroke in atrial fibrillation patients. Early initiation is safe and effective, potentially improving outcomes and suggesting guidelines may need revision.
Study Strengths and Limitations: Strengths include large sample size and masked outcome adjudication. Limitations include exclusion of patients with very severe strokes and low event rates, potentially limiting detection of rare adverse events.
Future Research: Further studies should explore optimal DOAC timing within 4 days and assess safety in patients with severe strokes or extensive haemorrhagic transformation.