Early DOAC after stroke reduces 30-day events

Start DOAC within 4 days after AF-related stroke.

Background

Optimal timing of direct oral anticoagulants (DOACs) after acute ischaemic stroke with atrial fibrillation (AF) is uncertain, balancing early embolic risk against haemorrhagic transformation.

Patients

5441 adults with acute ischaemic stroke and AF from four RCTs (TIMING, ELAN, OPTIMAS, START); mean age 77.7 years, 45% women, median NIHSS 5 (IQR 3–10).

Intervention

Early DOAC initiation ≤4 days after stroke onset (approved doses).

Control

Later DOAC initiation ≥5 days after onset (typically 5–14 days, trial-dependent).

Outcome

Primary: composite of recurrent ischaemic stroke, symptomatic intracerebral haemorrhage (sICH), or unclassified stroke within 30 days. Secondary: components of primary at 30 and 90 days; major extracranial haemorrhage; mortality; composite safety outcomes.

Study Design and Level of Evidence

Prospective individual participant data meta-analysis of randomised controlled trials; OCEBM Level 1a.

Follow up period

30 days (primary); 90 days (secondary).

Results

  • Primary (30 days): 2.1% early vs 3.0% later; OR 0.70 (95% CI 0.50–0.98). Absolute risk reduction 0.93%; NNT 108 (95% CI 55–2500).
  • Recurrent ischaemic stroke (30 days): 1.7% vs 2.6%; OR 0.66 (95% CI 0.45–0.96). Absolute risk reduction 0.87%; NNT 115.
  • sICH (30 days): 0.4% vs 0.4%; OR 1.02 (95% CI 0.43–2.46); no increase.
  • Major extracranial haemorrhage (30 days): 0.45% vs 0.55%; OR 0.82 (95% CI 0.38–1.75).
  • Mortality (30 days): 3.68% vs 4.36%; OR 0.83 (95% CI 0.63–1.09).
  • Primary composite (90 days): OR 0.88 (95% CI 0.65–1.19).
  • Consistency: Effects similar across stroke severity, reperfusion treatment, prior anticoagulation, sex, and age subgroups.

Limitations

  • Low sICH event rate limits precision.
  • Under-representation of very severe strokes/space-occupying haemorrhagic transformation.
  • Imaging confirmation of recurrence not mandated in three trials.
  • Heterogeneous timing schemes; some trial arms excluded to match ≤4 vs ≥5 days definition.
  • Limited ethnicity data.

Funding

Government

Citation

Dehbi H-M, Fischer U, Åsberg S, et al. Collaboration on the optimal timing of anticoagulation after ischaemic stroke and atrial fibrillation (CATALYST): systematic review and prospective IPD meta-analysis of RCTs. The Lancet. 2025;406:43–51. doi:10.1016/S0140-6736(25)00439-8.