People with AF at intermediate risk of stroke benefit from oral anticoagulants – SINGLE-AF Trial

Oral anticoagulant therapy lowered the risk of adverse clinical events compared with no anticoagulation in patients with atrial fibrillation (AF) at intermediate stroke risk, according to results from the SINGLE-AF trial presented in a Hot Line session at the ESC Congress 2026 and published simultaneously in the New England Journal of Medicine.

Patients with AF are at increased risk of suffering a stroke. ESC guidelines recommend oral anticoagulants for patients with AF at high risk of stroke with a Class I recommendation. The guidelines also suggest that oral anticoagulants should be considered in patients at intermediate risk, with a Class IIa recommendation.

Principal Investigator of the SINGLE-AF trial, Prof 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 randomised trial on whether newer direct oral anticoagulants (DOACs) are beneficial in patients with AF at intermediate risk of stroke.”

SINGLE-AF was an open-label trial conducted at 18 centres in South Korea. A total of 1,803 individuals with AF and an intermediate risk of stroke (defined as a CHA2DS2-VASc score of 1 in men or 2 in women) were randomised (1:1) to receive DOAC therapy (apixaban 5mg twice daily or rivaroxaban 20mg once daily) or to no anticoagulation.

At 24 months, a 69 per cent reduction in the primary endpoint – a composite of stroke, systemic embolism, major bleeding or cardiovascular death – was observed with DOACs vs no anticoagulation (0.5% and 1.5%, respectively; p=0.028; hazard ratio 0.31; 95% CI 0.10 to 0.94). The difference between the groups appeared to be driven by a lower incidence of ischaemic stroke with DOAC therapy (0.1%) vs no anticoagulant therapy (1.1%). There was no difference in major bleeding with DOAC therapy (0.3%) and without (0.5%).

Prof Joung concluded: “We now have evidence from a randomised 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.”

We now have evidence from a randomised trial that patients with AF at intermediate stroke risk benefit from DOAC therapy…