A large randomized trial suggests that newer anticoagulants may significantly reduce serious cardiovascular events in people with atrial fibrillation who face an intermediate risk of stroke.
The findings come from the SINGLE-AF trial, presented during a Hot Line session at the ESC 2026 Congress and published at the same time in the journal New England Journal of Medicine. Compared with no anticoagulant treatment, oral anticoagulant treatment was associated with fewer adverse clinical events.
A gray area in the treatment of atrial fibrillation
Atrial fibrillation (AF) is a common heart rhythm disorder that can increase the risk of blood clots and strokes. The ESC guidelines strongly recommend oral anticoagulants for people with AF who are considered at high risk for stroke. However, for those at intermediate risk, the recommendation is less definitive and anticoagulant treatment is currently listed as something that should be considered.
That uncertainty has persisted because previous observational research has produced mixed results, particularly for older vitamin K antagonist drugs.
Principal investigator of the SINGLE-AF trial, Professor 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 carried out 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. cerebrovascular”.
Trial of newer blood thinners
SINGLE-AF was an open-label study conducted at 18 medical centers in South Korea. Researchers enrolled 1,803 people with AF who were considered to be at intermediate risk for stroke (defined as a CHA2DS2-VASc score of 1 in men or 2 in women).
Participants were randomly assigned (1:1) to one of two groups. One group received direct oral anticoagulant treatment with 5 mg apixaban twice daily or 20 mg rivaroxaban once daily. The other group did not receive anticoagulation.
Serious events fell by 69%
After 24 months, the researchers found a 69% reduction in the trial’s primary endpoint among patients taking DOACs compared to those not receiving anticoagulation. The primary endpoint combined stroke, systemic embolism, major bleeding, and cardiovascular death.
Serious events occurred in 0.5% of patients receiving DOACs compared with 1.5% of those not receiving anticoagulant therapy (0.5% and 1.5%, respectively; p = 0.028; hazard ratio 0.31; 95% confidence interval 0.10 to 0.94).
The difference appeared to be largely due to fewer ischemic strokes. Ischemic stroke occurred in 0.1% of patients taking DOACs compared with 1.1% of those not receiving anticoagulation.
Importantly, the trial did not find an increase in serious bleeding. Major bleeding occurred in 0.3% of patients receiving DOAC treatment and 0.5% of those not receiving anticoagulation.
Findings Could Influence Future Guidelines
The results provide randomized evidence supporting the use of newer anticoagulants in a group of patients with atrial fibrillation for whom the benefits of anticoagulation have been less certain.
Professor Joung concluded: “We now have evidence from a randomized trial that AF patients at intermediate risk of stroke benefit from DOAC therapy, without an increase in major bleeding. Data from the SINGLE-AF trial can be used to inform future guideline recommendations and reimbursement policies.”