Abstract Body: BACKGROUND: Nearly one-quarter of ischemic strokes (IS) in the U.S. are recurrent. The purpose of this study is to determine the risk of recurrent IS associated with left ventricular fractional shortening (LVFS), a measure of LV dysfunction, in patients with cryptogenic stroke and atrial cardiopathy enrolled in the ARCADIA trial.

METHODS: We performed a post-hoc exploratory analysis in the ARCADIA trial, a phase III RCT of 1,015 cryptogenic stroke patients with atrial cardiopathy from February 2018 to February 2023. Those with LV ejection fraction <30% were not eligible. We dichotomized patients by LVFS <25% (reduced) and >25% (preserved). We built adjusted Cox proportional hazard models to estimate the hazard ratio (HR) of recurrent IS within each LVFS strata by treatment strategy of apixaban versus aspirin. We evaluated for heterogeneity of treatment effect by LVFS strata, assessing the statistical significance of the interaction term in the model with adjustment for imbalanced covariates.

RESULTS: The analytic cohort comprised 944 participants, with reduced LVFS in 128 (13.6%) and preserved in 816 (86.4%). Patients with reduced LVFS were significantly more likely to be male (56.2% vs 43.8%, p= 0.009), have higher rates of coronary artery disease (23.4% vs 8.1%, p<0.001) and CHF (18.8% vs 5.2%, p<0.001), higher N-terminal pro-Brain Natriuretic Peptide (median 376 vs 291 pg/mL, p<0.001), lower P-wave terminal force in V1 (median 4063 vs 5225 microVolts x ms, p=0.035), and larger left atrial diameter index (median 2.0 vs 1.9 cm, p=0.028). Recurrent IS occurred in 12 (9.4%) and 57 (7.0%) participants with reduced versus preserved LVFS, respectively. There was an interaction between treatment effect and LVFS strata (p=0.03; Figure). In the adjusted analysis, the risk of recurrent IS among patients with reduced LVFS randomized to apixaban vs aspirin was significantly reduced (HR 0.11, 95% C.I. 0.02-0.61), but there was no treatment effect in patients with preserved LVFS (HR 1.01 95% C.I. 0.59-1.73).

CONCLUSION: Apixaban, compared to aspirin, was associated with a reduction in risk of recurrent IS among patients with cryptogenic stroke, atrial cardiopathy, and reduced LVFS. Further study is needed to identify the optimal strategy to prevent recurrent stroke in cryptogenic ischemic stroke patients with LV dysfunction.