SINGLE-AF demonstrates DOAC therapy reduces clinical events in AF with intermediate stroke risk

Direct oral anticoagulant (DOAC) therapy reduced adverse clinical events compared with no anticoagulation in patients with atrial fibrillation (AF) at intermediate risk of stroke, according to results from the SINGLE-AF trial presented during a Hot Line session at ESC Congress 2026.¹

In the SINGLE-AF trial presented today at ESC Congress 2026, DOAC therapy reduced adverse clinical events in patients with AF at intermediate stroke risk.

Current ESC guidelines give a Class I recommendation for oral anticoagulation in patients with AF at high risk of stroke and state that anticoagulation should be considered in those at intermediate risk, with a Class IIa recommendation. However, evidence in the intermediate-risk population has largely come from observational studies.¹

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SINGLE-AF was an open-label randomized trial involving 1,803 patients at 18 centers in South Korea. Participants had AF and an intermediate stroke risk, defined as a CHA₂DS₂-VASc score of 1 in men or 2 in women, and were randomized 1:1 to receive DOAC therapy with apixaban or rivaroxaban or no anticoagulation.¹

At 24 months, the primary endpoint of stroke, systemic embolism, major bleeding or cardiovascular death occurred in 0.5% of patients receiving DOAC therapy compared with 1.5% receiving no anticoagulation, representing a 69% reduction in risk (HR 0.31; 95% CI 0.10–0.94; p=0.028).¹

The difference appeared to be driven by a lower incidence of ischemic stroke, occurring in 0.1% of the DOAC group versus 1.1% of the no-anticoagulation group. Major bleeding did not differ significantly between the groups, occurring in 0.3% and 0.5%, respectively.¹

“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,” said principal investigator Professor Boyoung Joung, Yonsei University, Seoul, South Korea. He added that the findings may help inform future guideline recommendations and reimbursement policies.¹

Discussing the findings following the presentation, Professor Isabelle Van Gelder described SINGLE-AF as “the study we were waiting for,” highlighting the previous lack of randomized evidence in this population. She nevertheless raised questions about generalizability, noting that participants were relatively young, predominantly male and recruited exclusively in South Korea.²

“Whether these findings also apply to older patients, to women and particularly to Caucasian Europeans remains uncertain,” she said.²

Van Gelder also noted that most strokes occurred in the no-anticoagulation group but were predominantly non-disabling, while two hemorrhagic strokes occurred in the DOAC group. She highlighted the relatively high use of antiplatelet therapy among patients not receiving anticoagulation as another factor that may have influenced the results.²

While describing a clear benefit with DOAC therapy, she cautioned that the overall number of events was considerably lower than anticipated, reducing the precision of the treatment-effect estimate.²

The SINGLE-AF trial was published simultaneously in the New England Journal of Medicine.¹

References

1. European Society of Cardiology. People with atrial fibrillation at intermediate risk of stroke benefit from oral anticoagulants. ESC Congress 2026 press release. August 28, 2026.
2. Joung B. SINGLE-AF: Anticoagulation for atrial fibrillation with intermediate stroke risk. Presented during Hot Line 1, ESC Congress 2026, Munich, Germany, August 28, 2026; discussion by Professor Isabelle Van Gelder.