N Engl J Med. 2026 Aug 28. doi: 10.1056/NEJMoa2607978. Online ahead of print.

ABSTRACT

BACKGROUND: Current U.S. and European guidelines recommend oral anticoagulation as a class IIa indication in patients with atrial fibrillation at intermediate risk for stroke; however, evidence from randomized trials is needed.

METHODS: We conducted a multicenter, open-label, adjudicator-masked superiority trial in South Korea involving patients with atrial fibrillation and an intermediate risk of stroke (a score of 1 in men and 2 in women on the CHA₂DS₂-VASc scale; range, 0 to 9, with higher scores indicating a greater risk of stroke). Patients were randomly assigned in a 1:1 ratio to receive either direct oral anticoagulant (DOAC) therapy or no anticoagulation. The primary end point was a composite of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months.

RESULTS: Of 1803 patients who underwent randomization, 902 were assigned to receive DOAC therapy and 901 were assigned to receive no anticoagulant therapy. The mean age of the patients was 60.4 years, and 23.7% were women. At 24 months, a primary end-point event had occurred in 4 patients (cumulative incidence, 0.5%) in the DOAC group and in 13 (cumulative incidence, 1.5%) in the no-anticoagulant group (difference, -1.0 percentage points; 95% confidence interval [CI], -2.0 to -0.1; P = 0.03; hazard ratio, 0.31; 95% CI, 0.10 to 0.94). Stroke occurred in 3 patients (cumulative incidence, 0.3%) in the DOAC group and in 10 (cumulative incidence, 1.1%) in the no-anticoagulant group. The incidence of systemic embolism and major bleeding appeared to be similar in the two trial groups, and no deaths from cardiovascular causes occurred in either group. Serious adverse events occurred in 80 patients (8.9%) in the DOAC group and in 84 (9.3%) in the no-anticoagulant group.

CONCLUSIONS: Among patients with atrial fibrillation at intermediate risk for stroke, DOAC therapy led to a lower risk of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months than no anticoagulation. (Funded by the Ministry of Health and Welfare, South Korea, and others; SINGLE-AF ClinicalTrials.gov number, NCT04437654.).

PMID:42663303 | DOI:10.1056/NEJMoa2607978