Atrial fibrillation raises the risk of blood clots and stroke, and guidelines strongly recommend blood thinners for patients at high stroke risk. For those at intermediate risk, the recommendation is weaker, in part because observational studies of older vitamin K antagonists have given conflicting results. The SINGLE-AF trial was designed to provide randomized evidence on whether newer direct oral anticoagulants (DOACs) help this group.
The open-label trial, conducted at 18 medical centers in South Korea, enrolled 1,803 people with atrial fibrillation and an intermediate stroke risk, defined as a CHA2DS2-VASc score of 1 in men or 2 in women. Participants were randomly assigned to receive either a DOAC (apixaban 5 mg twice daily or rivaroxaban 20 mg once daily) or no anticoagulation. After 24 months, the primary endpoint—a composite of stroke, systemic embolism, major bleeding, and cardiovascular death—occurred in 0.5% of the DOAC group versus 1.5% of the untreated group, a 69% relative reduction.
The difference was driven mainly by fewer ischemic strokes: 0.1% in the DOAC group versus 1.1% in the no-anticoagulation group. Major bleeding occurred in 0.3% of treated patients and 0.5% of untreated patients, indicating no increase in bleeding risk. The results were presented at ESC Congress 2026 and published in the New England Journal of Medicine.
The investigators said the findings provide the first randomized evidence that patients with atrial fibrillation at intermediate stroke risk benefit from DOAC therapy, and they may inform future guideline recommendations and reimbursement policies. The trial was open-label, but the size of the effect and the bleeding profile support the case for treatment in this previously uncertain group.