Our study investigated the “natural history” of cerebral events within the first two weeks after AF-related stroke or TIA, without therapeutic anticoagulation.

The AREST study (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was a multi-centered randomized controlled trial exploring the effect of early anticoagulation with apixaban (n=41) versus warfarin (n=47) in patients with AF and stroke/TIA between 2015 and 2019. We performed a subgroup analysis of the warfarin arm who: 1) by two weeks had not yet started anticoagulation, or were subtherapeutic (INR< 2); and 2) received brain MRI at 14 +/- 3 days. 

Among 18 patients who met above criteria, 1 had TIA, 2 had RIS, and 2 developed HT. Of these 5 events, only 2 were detected clinically (40%), whereas the remaining 3 (60%) were asymptomatic but with MRI identified 1 RIS and 2 HT. Initial NIHSS was low (0 and 1) in both RIS patients but high in both HT patients (10 and 13). One of the RIS patients initially had TIA and later had MRI-detected right frontal infarct, the other patient initially had a left hemispheric multifocal infarct and later developed bilateral emboli. Both HT were in the initial infarct bed and were PH1 and HI1.

A majority of recurrent cerebral events within the two-week time period after AF-related stroke/TIA are clinically asymptomatic and only detected radiographically. Tools designed for annual risk estimation may underestimate risk of RIS and/or HT during the two-week subacute phase.