Optimal Timing of Anticoagulation Initiation After Ischemic Stroke in Patients with AF

CLINICAL QUESTION: In patients with atrial fibrillation (AF) and acute ischemic stroke, does early anticoagulation initiation (within four days) improve outcomes compared to delayed initiation?

BACKGROUND: In patients with ischemic stroke and AF, early treatment with direct oral anticoagulants (DOACs) might reduce the risk of early ischemic stroke recurrence but might also increase hemorrhagic transformation of the acute infarct. Clinicians traditionally delayed anticoagulant initiation for one to two weeks after a stroke to prevent hemorrhagic transformation of the infarct.

SETTING: International collaboration involving data from four major trials (TIMING, ELAN, OPTIMAS, and START) conducted across multiple global centers

STUDY DESIGN: Systematic review and individual patient data meta-analysis

SYNOPSIS: The study included a total of 5,441 participants, comprising 2,691 patients with early DOAC initiation and 2,750 patients with later DOAC initiation. Early DOAC initiation was associated with a 30% reduction in the composite outcome of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke at 30 days (OR, 0.70; 95% CI, 0.50 to 0.98). When analyzing recurrent ischemic stroke alone at 30 days, the risk was reduced by 34% (OR, 0.66; 95% CI, 0.45 to 0.96). According to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, the certainty of evidence for both outcomes was rated as moderate due to imprecision. In contrast, when analyzing the risk of symptomatic intracerebral hemorrhage alone, no significant difference was observed between the early and later initiation groups (OR, 1.02; 95% CI, 0.43 to 2.46), with low certainty of evidence due to serious imprecision.

BOTTOM LINE: Early initiation of DOACs after ischemic stroke in patients with AF may reduce the risk of recurrent ischemic events without a clear increase in symptomatic intracerebral hemorrhage, although the certainty of evidence is limited.

CITATION: Dehbi HM, et al. Collaboration on the optimal timing of anticoagulation after ischaemic stroke and atrial fibrillation: a systematic review and prospective individual participant data meta-analysis of randomised controlled trials (CATALYST). Lancet. 2025;406(10498):43-51. doi: 10.1016/S0140-6736(25)00439-8.

Dr. Grondona is a hospitalist at the clinical medicine department at Hospital Aleman and an instructor of internal medicine at the University of Salvador, both in Buenos Aires, Argentina.