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INTRODUCTION: A recent meta-analysis, including the TIMING study, found favourable short-term outcomes after early initiation of a direct-acting oral anticoagulant (DOAC), as compared to delayed initiation, following acute ischaemic stroke in patients with atrial fibrillation. We aimed to investigate 1-year outcomes after early vs delayed DOAC initiation in the TIMING study population and a concurrent observational cohort.

PATIENTS AND METHODS: In TIMING, adults with atrial fibrillation were randomised to initiation of DOAC either within 4 days or at 5-10 days after acute ischaemic stroke. The non-randomised cohort comprised patients with acute ischaemic stroke and atrial fibrillation, observed in the Swedish Stroke Register concurrently with the TIMING study and initiating DOAC within 4 or 5-10 days, respectively. Outcomes in both populations were acute ischaemic stroke, symptomatic intracerebral haemorrhage or death, as a composite and individually, analysed using Cox regression models, with adjustment for risk factors in the observational cohort.

RESULTS: In the TIMING population (n = 888), the composite outcome at 365 days occurred in 64/450 patients (14.2%) with early DOAC initiation and 66/438 (15.1%) with delayed, unadjusted hazard ratio 0.92 (95% CI, 0.66-1.30). In the observational cohort (n = 8951), the composite outcome at 365 days occurred in 1227/6671 (18.4%) patients initiating DOAC early and 511/2280 (22.4%) in the delayed group, adjusted hazard ratio 0.80 (0.69-0.91).

DISCUSSION: At 1-year follow-up, early initiation of DOAC remained safe and effective with no increase in symptomatic intracerebral haemorrhage. The results support early DOAC initiation in patients with acute ischaemic stroke and atrial fibrillation.