Abstract Body: Introduction: The ARCADIA trial found no benefit of anticoagulation for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. The trial screened all patients with cryptogenic stroke, regardless of infarct topography. Acute brain infarction in multiple arterial territories could more strongly suggest a central embolic source. The recurrent stroke risk and role of apixaban versus aspirin in these patients is not well understood.

Hypothesis: Cryptogenic stroke patients with multi-territory infarction are at increased risk for recurrent stroke, and this population will benefit from treatment with apixaban compared to aspirin.

Methods: The ARCADIA trial screened patients with cryptogenic stroke for atrial cardiopathy at 185 centers in the U.S. and Canada. Among participants who met eligibility criteria for atrial cardiopathy and were randomly assigned to treatment assignment, we performed a subgroup analysis of those with multi-territory infarction, defined as acute infarction in at least two of the following territories: left anterior circulation, right anterior circulation, or posterior circulation. Cox models were used to compare stroke recurrence in patients with multi-territory versus single-territory infarction. Models were adjusted for age, sex, race, ethnicity, heart failure, coronary artery disease, peripheral artery disease, hypertension, diabetes, and tobacco use. We used tests of interaction to compare the effect of apixaban versus aspirin in patients in multi- versus single-territory infarcts.

Results: Of 1,015 randomized patients in ARCADIA, 123 had multi-territory infarction, of whom 55 (44.7%) received apixaban and 68 (55.3%) received aspirin. Risk of recurrent stroke was higher in patients who presented with multi-territory infarcts (HR 2.5, 95% CI 1.50-4.18). When adjusting for demographics and vascular risk factors, results were similar (HR 2.5, 95% CI 1.48-4.15). There was a similar lack of benefit of apixaban in patients with multi-territory infarct (HR 1.0, 95% CI 0.62-1.71) versus single-territory infarct (HR 1.0, 95% CI 0.43-2.51) (P for interaction = 0.98).

Conclusion: In patients with cryptogenic stroke and markers of atrial cardiopathy, multi-territory infarction was associated with an increased risk of recurrent stroke, but this population did not benefit from anticoagulation compared to aspirin.