The findings come from the SINGLE-AF trial, presented during a Hot Line session at ESC Congress 2026 and published at the same time in the New England Journal of Medicine. Compared with receiving no anticoagulant therapy, treatment with oral anticoagulants was associated with fewer adverse clinical events.

A Gray Area in Atrial Fibrillation Treatment

Atrial fibrillation (AF) is a common heart rhythm disorder that can increase the risk of blood clots and stroke. ESC Guidelines strongly recommend oral anticoagulants for people with AF who are considered at high risk of stroke. For those at intermediate risk, however, the recommendation is less definitive, and anticoagulant treatment is currently listed as something that should be considered.

That uncertainty has persisted because earlier observational research has produced mixed results, particularly for older vitamin K antagonist drugs.

Principal Investigator of the SINGLE-AF trial, Professor Boyoung Joung from Yonsei University, Seoul, South Korea, said: "Evidence from observational studies with anticoagulants, particularly vitamin K antagonists, remains conflicting in those at intermediate risk. SINGLE-AF was conducted to provide the first evidence from a randomized trial on whether newer direct oral anticoagulants (DOACs) are beneficial in patients with AF at intermediate risk of stroke."

Testing Newer Blood Thinners

SINGLE-AF was an open-label study carried out at 18 medical centers in South Korea. Researchers enrolled 1,803 people with AF who were considered to have an intermediate risk of stroke (defined as a CHA2DS2-VASc score of 1 in men or 2 in women).

Participants were randomized (1:1) to one of two groups. One group received direct oral anticoagulant treatment using either apixaban 5 mg twice daily or rivaroxaban 20 mg once daily. The other group received no anticoagulation.

Serious Events Fell by 69%

After 24 months, researchers found a 69% reduction in the trial's primary endpoint among patients taking DOACs compared with those receiving no anticoagulation. The primary endpoint combined stroke, systemic embolism, major bleeding, and cardiovascular death.

Serious events occurred in 0.5% of patients receiving DOACs compared with 1.5% of those receiving no anticoagulant therapy (0.5% and 1.5%, respectively; p=0.028; hazard ratio 0.31; 95% confidence interval 0.10 to 0.94).

The difference appeared to be driven largely by fewer ischemic strokes. Ischemic stroke occurred in 0.1% of patients taking DOACs compared with 1.1% of those receiving no anticoagulation.

Importantly, the trial did not find an increase in major bleeding. Major bleeding occurred in 0.3% of patients receiving DOAC therapy and 0.5% of those who did not receive anticoagulation.

Findings Could Influence Future Guidelines

The results provide randomized evidence supporting the use of newer blood thinners in a group of atrial fibrillation patients for whom the benefits of anticoagulation have been less certain.

Professor Joung concluded, "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. Data from the SINGLE-AF trial may be used to inform future guideline recommendations and reimbursement policies."