Anticoagulate the atrial fibrillation patient with a CHA2DS2-VASc of 1

Design

multicentre, open-label, adjudicator-masked, randomised superiority trial in South Korea (SINGLE-AF)

Population

1803 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 death from cardiovascular causes at 24 months

Effect

0.5% (4/902) with a DOAC vs 1.5% (13/901) with no anticoagulation, difference -1.0 percentage points (95% CI -2.0 to -0.1), HR 0.31 (95% CI 0.10 to 0.94), P=0.03

SINGLE-AF randomised 1803 South Korean patients with atrial fibrillation at intermediate stroke risk - a CHA2DS2-VASc score of 1 in men or 2 in women - to a direct oral anticoagulant or to no anticoagulation. It was open-label with masked endpoint adjudication. Mean age was 60.4 years and 23.7% were women. This is the group guidelines have called a class IIa 'may be considered', which in practice has meant the decision was made by whoever happened to be in clinic.

At 24 months the composite of stroke, systemic embolism, major bleeding or cardiovascular death had occurred in 4 patients on a DOAC (cumulative incidence 0.5%) and 13 on nothing (1.5%) - a difference of 1.0 percentage point (95% CI 0.1 to 2.0), hazard ratio 0.31 (95% CI 0.10 to 0.94), P=0.03. Stroke alone was 3 versus 10. Major bleeding and systemic embolism looked similar between arms, no cardiovascular deaths occurred at all, and serious adverse events were 8.9% versus 9.3%.

The direction is clear and the composite deliberately included bleeding, so the benefit is net rather than selective. But this rests on 17 events across 1803 patients over two years, in a relatively young Asian cohort, and a hazard ratio whose upper bound is 0.94 - statistically positive by a small margin. Treat it as the first randomised evidence for a decision that previously had none, enough to shift the default towards anticoagulating, not as a mandate.

• Recalculate CHA2DS2-VASc explicitly rather than relying on 'low risk' in an old letter - the score changes as patients age.
• Remember the sex adjustment: the trial's intermediate group is 1 point in men and 2 in women.
• Discuss it as a small absolute benefit - about 1 fewer event per 100 patients over two years - so the patient can weigh it honestly.
• Bleeding was inside the composite and did not increase, which is the reassuring part of the result.
• The cohort was Korean with a mean age of 60; extrapolate to much older or more comorbid patients with care.

The statistics, in plain English

A hazard ratio of 0.31 looks dramatic, but there were only 17 primary events in the whole trial, and a confidence interval running from 0.10 to 0.94 barely excludes 1.0. That fragility is the honest reading: one or two events falling differently would have made this non-significant. The absolute difference of 1.0 percentage point (95% CI 0.1 to 2.0) is the number to quote to a patient, because it does not inflate a rare outcome. It also matters that major bleeding was counted inside the primary composite rather than reported only as a harm - that design choice is why the result can be read as net benefit rather than a benefit that hides its cost.

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