Abstract Body: BACKGROUND: Nearly one-quarter of ischemic strokes (IS) in the U.S. are recurrent. We aimed to determine the risk of recurrent IS associated with reduced left ventricular ejection fraction (LVEF) in patients 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 LVEF <30% were not eligible. We dichotomized patients with LVEF into <50% and >50% and built adjusted Cox proportional hazard models to estimate the hazard ratio (HR) of recurrent IS within each LVEF strata by treatment strategy of apixaban versus aspirin. Significance of the interaction was assessed after adjustment for imbalanced covariates found among these groups.

RESULTS: The analytic cohort comprised 963 participants, with LVEF <50% in 74 (7.7%) and ≥50% in 889 (92.3%). Participants with LVEF<50% compared to >50% were younger (65 vs 68 years, p=0.006), more likely male (63.5% vs 44.4%, p=0.002) and of non-White race (45.9% vs 23.8%, p<0.001), and to have coronary artery disease (25.7% vs 8.9%, p<0.001) and CHF (33.8% vs 4.7%, p<0.001), higher N-terminal pro-BNP (median 487 vs 292 pg/mL, p<0.001), larger left atrial diameter index (median 2.1 vs 1.9 cm, p<0.001), and lower LVEF (median 43% vs 62%, p<0.001); P-wave terminal force in V1 was similar. Recurrent IS occurred in 10 (13.5%) patients with LVEF <50% and 61 (6.9%) with LVEF ≥ 50%. The incidence rates of recurrent stroke per 100 person-years were 7.1 (95% CI, 3.8-13.3) with LVEF <50% and 3.9 (95% CI, 3.0-5.0) with LVEF ≥ 50%. In the adjusted analysis, the risk of recurrent stroke was significantly higher with LVEF <50% vs ≥50% (HR 2.23, 95% CI 1.03-4.83). There was no significant interaction between LVEF stratum and the treatment effect (p=0.35; Figure). The risk of recurrent stroke was nominally lower among patients randomized to apixaban than aspirin with LVEF <50% (HR 0.11, 95% C.I. 0.01-1.12), and EF>50% (HR 0.87, 95% C.I. 0.52-1.45) but did not reach statistical significance.

CONCLUSION: Recurrent stroke risk was higher among patients with LVEF <50% vs ≥50%. The risk of recurrent stroke was not different among patients randomized to apixaban compared to aspirin. Further study is needed to identify the optimal anti-thrombotic treatment for patients with cryptogenic stroke and left ventricular dysfunction.