DOACs Win First Trial for Lower-Risk Afib
The SINGLE-AF trial found direct oral anticoagulants reduced cardiovascular events in atrial fibrillation patients with a single stroke risk factor, though
Direct oral anticoagulant (DOAC) therapy reduced cardiovascular events compared to no anticoagulation in atrial fibrillation patients with one stroke risk factor, according to new trial data. The results from the SINGLE-AF trial were presented by Boyoung Joung, MD, of Yonsei University at this year's European Society of Cardiology meeting in Munich and published in the New England Journal of Medicine.
At 24 months, the composite cardiovascular event rate was 0.5% for patients on DOACs versus 1.5% for those on no anticoagulation. This yielded a hazard ratio of 0.31. The trial is the first randomized study to show a clinical benefit for DOACs in this intermediate-risk patient group.
Trial Results and Cautions
However, the annual stroke incidence was very low: 0.6% without anticoagulation and 0.15% with DOACs. The study authors, led by Joung, warned that the low number of endpoint events limits the precision of the estimated treatment effect. They stated the findings should be interpreted with caution.
The individual components of the primary endpoint showed inconclusive results due to these low rates. Stroke occurred in 0.3% of the DOAC group and 1.1% of the control group. Rates of systemic embolism and major bleeding appeared similar between the two groups. No cardiovascular deaths occurred in either arm of the trial.
Patient Population and Treatment
The SINGLE-AF trial specifically enrolled patients with atrial fibrillation and a CHA2DS2-VASc score of 1 for men or 2 for women. This represents a single risk factor beyond female sex, such as hypertension, diabetes, or age 65 or older. The trial randomized 1,803 participants in South Korea between 2020 and 2023.
The cohort had a mean age of 60.4 years and was 23.7% women. Most atrial fibrillation was paroxysmal. The most commonly prescribed DOAC was apixaban 5 mg. The majority of patients assigned to DOACs received a full dose.
| Characteristic | Value |
|---|---|
| Mean Age | 60.4 years |
| Percentage Women | 23.7% |
| Median CHA2DS2-VASc Score | 1 |
| Mean CHA2DS2-VASc Score | 1.3 |
| Median HAS-BLED Score | 0 |
| Mean HAS-BLED Score | 0.5 |
| Paroxysmal Afib | 71.8% |
| Median Time Since Diagnosis | 21 months |
Context and Commentary
DOACs are a first-line therapy for patients with two or more stroke risk factors. For intermediate-risk patients, U.S. guidelines currently give DOAC therapy a modest class IIa recommendation. In an editorial, Paulus Kirchhof, MD, noted that anticoagulation increases bleeding risk by 60 to 100% compared to no therapy.
Kirchhof suggested the SINGLE-AF results may encourage anticoagulation use in patients with a single risk factor. He also pointed to future options like factor XI inhibitors, which may offer a safer profile. The trial's open-label design may have introduced bias, and its results may not generalize beyond East Asian populations. Serious adverse events occurred in 8.9% of the DOAC group and 9.3% of the control group, with Afib-related hospitalization being the most common. You can explore more detailed stats on cardiovascular trial outcomes.
