MUNICH — Direct oral anticoagulant (DOAC) therapy reduced the risk for adverse clinical events by 69% compared with no anticoagulation in patients with atrial fibrillation (AF) who are at intermediate risk for stroke, according to results of the randomized SINGLE-AF trial.
At 24 months, the primary composite endpoint of stroke, systemic embolism, major bleeding, or cardiovascular death occurred in 0.5% of patients receiving a DOAC compared with 1.5% of those receiving no anticoagulation.
“We now have evidence from a randomized trial that patients with AF at intermediate stroke risk benefit from DOAC therapy, without an increase in major bleeding,” said senior author and presenter Boyoung Joung, MD, a professor of cardiology at Yonsei University College of Medicine in Seoul.
“The [prior] level of evidence in this population is actually very low, based on observational studies, and the results vary a lot,” Joung said, noting that evidence for other anticoagulants, particularly vitamin K antagonists, has remained conflicting in patients at intermediate risk. “This is the first randomized controlled trial to support that DOAC therapy can really provide a benefit to this patient population.”
The findings were presented at the European Society of Cardiology (ESC) Congress 2026 and simultaneously published in The New England Journal of Medicine.
Evidence Gap in Intermediate-Risk AF
Current US and European guidelines strongly recommend oral anticoagulation for men with a CHA ₂ DS ₂ -VASc score of 2 or more and women with a score of 3 or more.
For patients at intermediate risk for stroke, defined as a CHA ₂ DS ₂ -VASc score of 1 in men and 2 in women, anticoagulation should be considered (a class IIa recommendation). However, randomized evidence supporting treatment in this group has been limited and conflicting.
SINGLE-AF was a multicenter, open-label, randomized superiority trial conducted in South Korea. The trial included 1803 patients randomly assigned 1:1 to DOAC therapy or no anticoagulant therapy. In the DOAC group, 67.4% were assigned apixaban 5 mg twice daily, 14.1% were assigned rivaroxaban 20 mg once daily, and 13.9% were assigned rivaroxaban 15 mg once daily. Mean age of the entire cohort was 60.4 years, 23.7% were women, and 71.8% had paroxysmal AF. The median time from AF diagnosis to randomization was 21 months.
Of those on DOAC therapy, 81.6% received full doses and 18.4% received reduced doses. During the trial, 5.5% of patients assigned to no anticoagulation received a DOAC.
Antiplatelet therapy was used