Apixaban and Recurrent Stroke Risk With Left Ventricular Dysfunction: A Secondary Analysis of the ARCADIA Trial.

Background: Major uncertainty remains about the relationship between left ventricular (LV) systolic dysfunction, recurrent stroke, and the optimal antithrombotic therapy for secondary stroke prevention in patients with recent stroke and LV systolic dysfunction.

Methods: We performed a post hoc analysis of data from the ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke), a randomized trial comparing apixaban versus aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. Echocardiograms were sent from 185 enrolling sites in the United States and Canada for central review at the trial echocardiography laboratory. We defined LV systolic dysfunction as LV fractional shortening <25%, LV ejection fraction <50%, or any LV wall motion abnormality. The primary outcome of interest was recurrent ischemic stroke. First, we built Cox proportional hazard models to evaluate the association between LV systolic dysfunction and recurrent ischemic stroke risk adjusted for imbalanced covariates. Next, we used Cox proportional hazard models and interaction terms to compare the effect of apixaban versus aspirin on the outcome of interest in patients with and without LV systolic dysfunction.

Results: Among 964 patients with complete echocardiographic data of the 1015 patients enrolled in the trial, 165 (17.1%) had LV systolic dysfunction (mean age, 67 years; 43% female; mean follow-up, 1.7 years), and 799 (82.9%) had no LV systolic dysfunction (mean age, 68 years; 56% female; mean follow-up, 1.5 years). Recurrent ischemic stroke occurred more frequently in patients with LV systolic dysfunction (n=15, 9.1%) compared with those without LV systolic dysfunction (n=50, 6.3%), but LV systolic dysfunction was not significantly associated with recurrent stroke after adjustment for imbalanced covariates (hazard ratio, 1.3 [95% CI, 0.7-2.4]). Compared with aspirin, apixaban was associated with a significantly reduced risk of recurrent ischemic stroke in patients with LV systolic dysfunction (hazard ratio, 0.24 [95% CI, 0.07-0.87]) but not in those without LV systolic dysfunction (hazard ratio, 1.13 [95% CI, 0.65-1.96]; P_interaction=0.028).

Conclusions: In a secondary analysis of the ARCADIA trial data, apixaban was associated with a significantly lower risk of recurrent ischemic stroke than aspirin in patients with LV systolic dysfunction.