Prevention of Arterial Thromboembolism in Non-valvular Atrial Fibrillation trial (1999)


Prevention of arterial thromboembolism in low risk patients with AF

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To investigate the effectiveness of ASA and warfarin in preventing thromboembolic events in patients with non-rheumatic AF in general practice

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Trial design

Randomized, controlled trial
Active treatment:

  • Stratum 1 (394 patients eligible for standard anticoagulation): standard warfarin (INR 2.5–3.5; n=131) vs. very low intensity warfarin
    (INR 1.1–1.6; n=122)
  • Stratum 2 (335 patients ineligible for standard anticoagulation): low intensity warfarin (INR 1.1–1.6; n=157)

Control treatment: ASA 150 mg once daily (stratum 1: n=141; stratum 2: n=178)

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Primary endpoint: stroke, systemic arterial embolism, major hemorrhage, vascular death
Secondary endpoints: non-fatal myocardial infarction, retinal infarction, TIA, minor bleeding, non-vascular death

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Trial participants

729 patients aged >60 years with AF and no established indication for warfarin, recruited in general practice

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Primary outcome: Mean follow-up was 2.7 years with a total of 1939 patient-years. In total 108 primary events occurred: 30 in stratum 1 and 78 in stratum 2. 10 events in stratum 1 occurred in the standard warfarin group (2% per year), 8 in the low intensity warfarin group (2% per year) and 12 in the ASA group (3% per year). 37 events in stratum 2 occurred in the low intensity warfarin group (10% per year) and 41 in the ASA group (10% per year). The average total annual event rate was 5.5%. Compared with ASA, the hazard ratio was 0.91 for low intensity warfarin (both strata) and 0.78 for standard warfarin (stratum 1)
Safety outcome: The total annual bleeding rate was 3.9%: 1.2% for major or fatal bleeding (n=23) and 2.7% for minor bleeding (n=52). 17 of the major bleeds occurred in stratum 2, with 10 in the ASA group. Between treatment groups no significant difference in risk of bleeding was found

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Efficacy: In a general practice population (without established indications for warfarin) neither low intensity nor standard warfarin treatment is better than ASA in preventing stroke, systemic arterial embolism, major hemorrhage or vascular death
Safety: There were no significant differences between groups in bleeding incidence

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Hellemons BSP, Langenberg M, Lodder J, Vermeer F, Schouten HJA, Lemmens T, van Ree JW, Knottnerus JA. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin. Br Med J 1999;319:958-964

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Corresponding author

BSP HellemonsBoode, MD, Department of General Practice, University of Maastricht, PO Box 616, 6200 MD Maastricht, Netherlands, e-mail: Bep.Hellemons@HAG.Unimaas.NL

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