SINGLE-AF: Oral Anticoagulants Reduce Risk of Stroke in Patients With AF

Patients with atrial fibrillation (AF) who are at intermediate risk of stroke experience benefits in stroke, systemic embolism, major bleeding, and cardiovascular death risk with oral anticoagulants.¹

Presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by lead investigator Boyoung Joung, MD, professor of internal medicine in the cardiology division and director of the cardiac electrophysiology laboratory and the bio-drug development laboratory at Yonsei University College of Medicine in South Korea, these data reflect the first randomized trial confirming the efficacy of oral anticoagulants in this patient population.¹

“Evidence from observational studies with anticoagulants, particularly vitamin K antagonists, remains conflicting in those at intermediate risk,” Joung said in a statement. “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.”¹

Oral Anticoagulants in the Guidelines

Current ESC guidelines recommend oral anticoagulants for patients with AF at high risk of stroke with a Class I recommendation. Additionally, oral anticoagulants should be considered in patients at intermediate risk with a Class IIa recommendation, according to the guidelines. To effectively support these recommendations, Joung and colleagues conducted the SINGLE-AF trial.¹

SINGLE-AF was an investigator-initiated, multicenter, open-label, adjudicator-masked, superiority randomized trial. Patients were eligible if they were between 19 and 80 years with AF and a CHA2DS2-VASc score of 1 (male) or 2 (female). Patients with significant liver or renal disease, structural heart disease, active malignancy, or who required anticoagulation due to surgery were excluded.²

The primary endpoint was a composite of stroke, systemic embolism, major bleeding, and cardiovascular death over 24 months. Secondary outcomes included each individual component of the primary endpoint, as well as transient ischemic attack, myocardial infarction, and hospital admission over the same period, and clinically relevant non-major bleeding (CRNMB). This last was defined as either any sign or symptom of hemorrhage or ISTH major bleeding in non-surgical patients.²

Evidence to Support Anticoagulants

A total of 1803 patients were ultimately enrolled and were randomly assigned in a 1:1 ratio to receive either DOAC therapy - in the form of apixaban 5 mg twice daily or rivaroxaban 20 mg once daily – or to standard treatment without anticoagulation. After 24 months, Joung and colleagues saw a 69% reduction in the composite primary endpoint among patients receiving DOACs versus those with no anticoagulation (0.5% and 1.5%, respectively; P = .028; HR, 0.31; 95% CI, 0.1-0.94).¹

The team concluded that this difference was driven by a lower incidence of ischemic stroke with DOAC therapy (0.1%) versus no anticoagulation (1.1%). Additionally, no difference in major bleeding was noted between those receiving DOAC (0.3%) and those without (0.5%).¹

“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,” Joung said in a statement. “Data from the SINGLE-AF trial may be used to inform future guideline recommendations and reimbursement policies.”¹

References

1. Joung B. SINGLE-AF: Anticoagulation for atrial fibrillation with intermediate stroke risk. Presented at the European Society of Cardiology Congress 2026, Munich, Germany. August 28-31, 2026.

2. Yonsei University. The Efficacy and Safety of Non-vitamiN K antaGonist oraL Anticoagulants for intermEdiate Stroke Risk in Patients With Atrial Fibrillation (SINGLE-AF). ClinicalTrials.gov Identifier: NCT04437654. Updated July 7, 2026. Accessed August 28, 2026. https://clinicaltrials.gov/study/NCT04437654