BACKGROUND
Rivaroxaban and dabigatran were not superior to aspirin in patients with embolic stroke
of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin
in ESUS patients with risk factors for cardio-embolism.
METHODS
Multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice
daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in
patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale.
Cardiac monitoring was mandatory and aspirin treatment was switched to apixaban in
case of atrial fibrillation detection. The primary outcome was any new ischemic lesion
on brain MRI during 12-month follow-up. Secondary outcomes included major and
clinically relevant non-major bleeding.
RESULTS
352 patients were randomized to receive apixaban (178 patients) or aspirin (174
patients) at a median of 8 days after ESUS. New ischemic lesions occurred in 23
(13.6%) participants in the apixaban group and in 25 (16.0%) in the aspirin group
(adjusted odds ratio 0.79; 95% CI, 0.42 to 1.48; P=0.57). Major and clinically relevant
non-major bleeding occurred in 5 and 7 participants (one-year cumulative incidence,
2.9 and 4.2) (hazard ratio 0.68; 95% CI, 0.22 to 2.16). Serious adverse event rates
were 43.9 per 100 person-years on apixaban and 45.7 on aspirin. ATTICUS was
terminated after a prespecified interim analysis due to futility.
CONCLUSIONS
Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing
new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers
Squibb/Pfizer and Medtronic; ATTICUS ClinicalTrials.gov number, NCT02067182)
