A direct oral anticoagulant reduced events at intermediate stroke risk in atrial fibrillation

Design

Multicentre, randomised, open-label, adjudicator-masked superiority trial (SINGLE-AF)

Population

1,803 patients with atrial fibrillation and CHA2DS2-VASc of 1 (men) or 2 (women), South Korea

Primary outcome

Stroke, systemic embolism, major bleeding or cardiovascular death at 24 months

Effect

0.5% vs 1.5%; HR 0.31 (95% CI 0.10 to 0.94)

US and European guidelines give a weaker (class IIa) recommendation for anticoagulation in atrial fibrillation at intermediate stroke risk, CHA2DS2-VASc of 1 in men or 2 in women, because randomised evidence was lacking. SINGLE-AF, published in August in the New England Journal of Medicine, randomised 1,803 such patients in South Korea (mean age 60, 24% women) to a direct oral anticoagulant or no anticoagulant, open label with masked adjudication.

At 24 months, the composite of stroke, systemic embolism, major bleeding or cardiovascular death occurred in 0.5% on a DOAC and 1.5% without (difference −1.0 percentage point, 95% CI −2.0 to −0.1; HR 0.31, 0.10 to 0.94). Strokes were 0.3% vs 1.1%. Major bleeding and embolism looked similar, and there were no cardiovascular deaths in either group.

The benefit is real but rests on 17 events in total, so its size is uncertain. What it does is move the intermediate-risk decision from expert opinion to trial evidence: on these data, offering a DOAC to such a patient is supported, with bleeding risk assessed as usual. It was an East Asian, relatively young population, and the guideline recommendation itself has not yet changed.

• Offer a direct oral anticoagulant to patients with atrial fibrillation at CHA2DS2-VASc 1 (men) or 2 (women) after discussing bleeding risk.
• Assess and correct modifiable bleeding risks, such as uncontrolled blood pressure or NSAID use, before starting.
• Explain that absolute benefit is about one fewer event per 100 patients over two years.
• Reassess the score at each review; many intermediate-risk patients become high risk with age.

Why it matters

It gives randomised evidence for a decision guidelines left to judgement.

Don't overread it

Few events, an open-label design and a Korean population limit how far the effect size can be generalised; guidelines have not yet changed.

The statistics, in plain English

With only 4 vs 13 events, the hazard ratio of 0.31 has a wide interval (0.10 to 0.94): the true benefit could be large or modest. The absolute difference of about 1 percentage point over two years means roughly 100 patients treated for two years to prevent one event.

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