Apixaban increased overall major bleeding in SCAF, with GI bleeding accounting for most of the excess risk compared with aspirin. JAMA Cardiology reported a prespecified ARTESiA subanalysis evaluating the characteristics and predictors of major bleeding.

The trial included 3961 patients with SCAF lasting 6 to 24 minutes and elevated stroke risk. Treatment involved apixaban 5 mg twice daily, with a 2.5 mg twice-daily adjustment when indicated, or aspirin 81 mg once daily. Major bleeding events were adjudicated according to International Society on Thrombosis and Hemostasis (ISTH) criteria. The mean follow-up duration was 3.5 years.

Major bleeding occurred in 86 of 1989 apixaban users and 47 of 1972 aspirin users, corresponding to 1.71 and 0.94 events per 100 patient-years (hazard ratio [HR] 1.80; 95% confidence interval [CI] 1.26–2.57). Intracranial bleeding rates were similar between groups at 0.33 and 0.40 per 100 patient-years (HR 0.82; 95% CI 0.43–1.57), while gastrointestinal (GI) bleeding occurred more frequently with apixaban (HR 2.23; 95% CI 1.32–3.78). Apixaban-related events were less likely to occur at critical sites.

NSAID use (HR 10.25), cancer (HR 2.87), apixaban therapy (HR 1.84), and older age (HR 1.47 per 5-year increase) demonstrated strong associations with increased major bleeding risk.