Apixaban Versus Aspirin and Risk of Hemorrhage in the ARCADIA Trial.

OBJECTIVE

The relative risks of bleeding with apixaban and aspirin remain unclear. We compared bleeding end points on apixaban versus aspirin in the ARCADIA trial.

METHODS

ARCADIA was a multicenter, double-blind, randomized trial of apixaban versus aspirin in patients with cryptogenic stroke and evidence of atrial cardiopathy. International Society on Thrombosis and Hemostasis (ISTH) criteria were used to classify bleeding as intracranial, symptomatic intracranial, major non-intracranial hemorrhages, and any major and minor hemorrhages. We calculated annualized incidence rate differences (IRDs) between apixaban and aspirin. Our primary analysis included the safety sample which censored patients who permanently stopped taking the study drug. Sensitivity analyses included the intention-to-treat sample.

RESULTS

Among 1,015 patients assigned to apixaban or aspirin and followed for a mean 1.8 (±1.2) years, 115 (11.3%) patients experienced 146 hemorrhages: 27 (18.5%) major and 119 (81.5%) minor hemorrhages. Apixaban resulted in significantly fewer intracranial hemorrhages than aspirin in both the safety sample (IRD = -1.4%, 95% confidence interval [CI] = -2.3% to -0.5%) and intention-to-treat sample (IRD = -1.0%, 95% CI = -1.8% to -0.2%). Findings were similar for the risk of symptomatic intracranial hemorrhage in the safety sample (IRD = -1.1%, 95% CI = -1.8% to -0.3%), although this was not statistically significant in the sensitivity analysis of the intention-to-treat sample (IRD = -0.7%, 95% CI = -1.4% to 0.0%, p = 0.11). Risks of major non-intracranial hemorrhage, any major hemorrhage, and minor hemorrhage did not differ significantly between apixaban and aspirin.

INTERPRETATION: We found no increase in any hemorrhage type and a decrease in intracranial hemorrhage with apixaban relative to aspirin in patients with cryptogenic stroke and evidence of atrial cardiopathy. ANN NEUROL 2026;99:1589-1597.