SINGLE-AF Trial Finds Blood Thinners Cut Events by 69% in Intermediate-Risk AF Patients

Patients with atrial fibrillation (AF) at intermediate risk of stroke benefit from oral anticoagulant therapy, according to results from the SINGLE-AF trial presented at the European Society of Cardiology (ESC) Congress 2026 and published simultaneously in the New England Journal of Medicine. Current ESC guidelines give a strong recommendation for anticoagulants in AF patients at high stroke risk, but only suggest considering them for patients at intermediate risk, based on evidence the trial's investigators called conflicting.

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

The open-label trial, conducted at 18 centers in South Korea, randomized 1,803 people with AF and an intermediate stroke risk to receive DOAC therapy — apixaban 5 mg twice daily or rivaroxaban 20 mg once daily — or no anticoagulation. At 24 months, a composite endpoint of stroke, systemic embolism, major bleeding or cardiovascular death occurred in 0.5% of patients on DOACs compared with 1.5% of those without anticoagulation, a 69% relative reduction.

The difference was driven largely by a lower rate of ischemic stroke with DOAC therapy (0.1%) versus no anticoagulation (1.1%), while major bleeding rates were similar between the two groups (0.3% versus 0.5%).

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