SINGLE-AF: anticoagulation helps at CHA2DS2-VASc 1, on very few events

Design

multicentre, open-label, adjudicator-masked randomised superiority trial in South Korea

Population

1,803 patients with atrial fibrillation at intermediate stroke risk (CHA2DS2-VASc 1 in men, 2 in women); mean age 60.4 years, 23.7% women

Primary outcome

composite of stroke, systemic embolism, major bleeding or cardiovascular death at 24 months

Effect

0.5% (4 patients) vs 1.5% (13 patients); difference −1.0 percentage points (95% CI −2.0 to −0.1), HR 0.31 (0.10–0.94), p=0.03

Anticoagulation for atrial fibrillation at a CHA2DS2-VASc score of 1 in men or 2 in women has been a class IIa recommendation — 'should be considered' — with no randomised evidence behind it. SINGLE-AF supplied some. It randomised 1,803 patients in South Korea, mean age 60.4 years and 23.7% women, to a direct oral anticoagulant or to no anticoagulation, open-label with masked adjudication, over 24 months.

The composite of stroke, systemic embolism, major bleeding or cardiovascular death occurred in 4 patients on a DOAC (0.5%) and 13 on none (1.5%): a difference of 1.0 percentage points (95% CI −2.0 to −0.1), hazard ratio 0.31 (0.10–0.94), p=0.03. Stroke accounted for most of it, 3 against 10. Major bleeding and systemic embolism were similar between groups, no cardiovascular deaths occurred in either, and serious adverse events were 8.9% against 9.3%.

So the direction is clear and the magnitude is what you would expect at this risk level: a stroke prevented for roughly every hundred patients treated for two years. The fragility is equally clear. Seventeen events decided this trial. A handful of events reallocated would move the hazard ratio across 1.0, the upper confidence bound sits at 0.94, and the population was young, Korean and mostly male. This is the first randomised answer to a real question, not a settled one.

• It supports offering anticoagulation at CHA2DS2-VASc 1 in men and 2 in women, as a discussion rather than a default.
• Mean age was 60.4 years — the bleeding risk that makes this decision difficult rises steeply above that, and this trial does not address it.
• Bleeding was similar between arms, but 24 months is short for accumulating anticoagulant bleeding and the population was young.
• Twenty-three per cent were women, so the female arm of the question rests on a small number of patients.
• DOACs are widely available as generics in India at a cost that makes this a realistic offer; warfarin, with the monitoring it requires, is a different calculation at this level of benefit.

Why it matters

The commonest borderline anticoagulation decision in an arrhythmia clinic has been made on guideline consensus alone until now.

Don't overread it

Seventeen events decided this trial, in a young, largely male, single-country population — it establishes a direction, not a magnitude.

The statistics, in plain English

This trial turned on 17 events in 1,803 patients, which is about as fragile as a positive result gets: the hazard ratio of 0.31 has a confidence interval reaching to 0.94, meaning the data are compatible with a benefit close to nothing. The absolute difference of 1.0 percentage points over 24 months is the number to quote to a patient, not the 69% relative reduction. And with no cardiovascular deaths and similar bleeding, the composite was effectively a stroke endpoint — which is cleaner than most composites, but means the bleeding side of the trade-off was never really tested.

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