In patients with atrial fibrillation (AFib) at intermediate risk for stroke, DOAC therapy resulted in a lower risk of stroke, systemic embolism, major bleeding or death from cardiovascular causes at 24 months compared with no anticoagulation. These findings from the SINGLE-AF trial were presented at ESC Congress 2026 and simultaneously published in NEJM.

Researchers randomized 1,803 patients at multiple centers in South Korea to receive either DOAC therapy (apixaban 5 mg twice daily or rivaroxaban 20 mg once daily) or no anticoagulation. The mean age of participants was 60 years and nearly 24% were women.

At 24 months, a 69% reduction in the cumulative incidence of stroke, systemic embolism, major bleeding, or death from cardiovascular causes was observed with DOACs compared with no anticoagulation (0.5% and 1.5%, respectively; p=0.028; hazard ratio 0.31; 95% confidence interval 0.10 to 0.94). According to study investigators, the difference appeared to be driven by a lower rate of ischemic stroke.

Broken down by event, three patients in the DOAC group vs. 10 in the no anticoagulation experienced a stroke, while the incidence of systemic embolism and major bleeding was similar in both groups. There were no deaths from cardiovascular causes in either group; however, researchers noted similar rates of adverse events across both groups (8.9% in the DOAC group vs. 9.3% in the no anticoagulation group).

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

Joung and colleagues highlight the importance of the SINGLE-AF trial in contributing to evidence showing benefits from DOAC therapy without an increase in major bleeding. However, they also stress the findings should be interpreted with caution "given the lower-than-expected number of end-point events" and small sample size.

In a related editorial comment, Paulus Kirchhof, MD, notes the trial's limitations, but says "within the context of the results ... the use of anticoagulation inpatients with AFib and a single risk factor for stroke may be encouraged." However, he also writes that "in patients with a low AFib burden, no therapy may be preferred" and that "additional treatment options for patients with a single risk factor for stroke may emerge in the coming years, including therapeutic reduction of AFib burden and new antithrombotic therapies."

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: ESC Congress, ESC26, Atrial Fibrillation, Stroke, Thromboembolism, Anticoagulants