Stroke Prevention in Atrial Fibrillation III study (1996)


Prevention of stroke and systemic embolism in high-risk patients with AF

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To compare the efficacy and safety of a low-intensity fixed-dose warfarin/ASA combination with adjusted-dose warfarin in the prevention of stroke and systemic embolism

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Trial design

Randomized, controlled, open-label study
Active treatment: low-intensity fixed-dose warfarin (initially adjusted to INR 1.2–1.5) combined with ASA (325 mg once daily) (n=521)
Control treatment: adjusted-dose warfarin (INR 2.0–3.0) (n=523)

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Primary efficacy endpoint: ischemic stroke or systemic embolism
Secondary efficacy endpoints: TIA, disabling/fatal strokes, myocardial infarction, death
Primary safety endpoints: major hemorrhage, intracranial hemorrhage

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Trial participants

1044 patients (mean age 72 years) with AF and at least one thromboembolic risk factor

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Efficacy outcome: At the time of an interim analysis after a mean follow-up of 1.1 years a primary event had occurred in 44 of 521 patients (7.9% per year) receiving low-dose warfarin plus ASA compared to 11 of 523 patients (1.9% per year) receiving adjusted standard-dose warfarin (absolute risk reduction 6.0% per year and relative risk reduction 74% by adjusted-dose warfarin). The study was stopped due to the excess of strokes in the low-dose warfarin group
Safety outcome: Major hemorrhage occurred in 13 of 521 patients receiving low-dose warfarin plus ASA (2.4% per year) and in 12 of 523 patients receiving adjusted-dose warfarin (2.1% per year). Also the rates of intracranial bleeding were similar in both treatment groups

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Efficacy: In high-risk AF-patients, low-intensity, fixed-dose warfarin plus ASA was inferior to adjusted standard-dose warfarin in reducing

  • ischemic stroke and systemic embolism
  • disabling stroke
  • ischemic stroke, systemic embolism and vascular death

Safety: The rates of major and intracranial bleeding were similar in both groups

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Blackshear L, Halperin JL, Hart RG, Laupacis A, McAnulty JH, McBride R. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996;348:633-638

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Corresponding author

Ruth McBride, Statistics and Epidemiology Research Corporation, 1107 NE 45th Street, Suite 520, Seattle, WA 98105

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