Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually
be detected only by long-term continuous monitoring with pacemakers or defibrillators.
Subclinical atrial fibrillation is associated with an increased risk of stroke by
a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit.We
conducted a trial involving patients with subclinical atrial fibrillation lasting
6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy
design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when
indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued
and anticoagulation started if subclinical atrial fibrillation lasting more than 24
hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke
or systemic embolism, was assessed in the intention-to-treat population (all the patients
who had undergone randomization); the primary safety outcome, major bleeding, was
assessed in the on-treatment population (all the patients who had undergone randomization
and received at least one dose of the assigned trial drug, with follow-up censored
5 days after permanent discontinuation of trial medication for any reason).We included
4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score
of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk
of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years,
stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per
patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard
ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment
population, the rate of major bleeding was 1.71% per patient-year in the apixaban
group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI,
1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group
and 8 patients in the aspirin group.Among patients with subclinical atrial fibrillation,
apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but
a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research
and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).
