Infarct volume was not associated with differences in outcomes between early and delayed direct oral anticoagulant (DOAC) initiation after atrial fibrillation (AF)-related ischemic stroke in a prespecified analysis of the OPTIMAS trial, published in the International Journal of Stroke.

OPTIMAS was a randomized, parallel-group, open-label trial with blinded outcome assessment that evaluated timing of DOAC initiation after acute ischemic stroke in patients with AF.

Participants were randomized to early DOAC initiation within 4 days of stroke onset or delayed initiation between 7 and 14 days. This prespecified secondary analysis included 3,572 participants (mean age 78±10 years; 45% female), representing 98.6% of the trial population.
Infarct volume was determined centrally using diffusion-weighted magnetic resonance imaging (MRI) with validated deep learning segmentation or manual segmentation on computed tomography (CT). Infarct volume was modeled as a continuous variable using restricted cubic splines, with interaction testing between infarct size and treatment allocation.

The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (ICH), and systemic arterial embolism within 90 days. Across infarct volume categories, no interaction was observed between infarct size and anticoagulation timing (pinteraction=0.18). Event rates varied across infarct strata without a consistent difference between early and delayed initiation. Corresponding odds ratios ranged from 0.13 (95% confidence interval [CI]: 0.02–1.11) to 1.52 (95% CI: 0.71–3.20) across infarct categories.

Symptomatic ICH rates were not higher with early anticoagulation, including among participants with larger infarcts (>25 mL), with 3/238 (1.3%) events in the early group and 5/239 (2.1%) in the delayed group.

The treatment effect of early versus delayed DOAC initiation did not vary with infarct volume in patients with AF-related ischemic stroke.