Long-term Anticoagulation for a First episode of Idiopathic venous Thromboembolism (1999)


Long-term prevention of recurrent idiopathic VTE

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To determine the effects of extending a 3-month course of oral anticoagulant therapy for a further 24 months on the rates of recurrent symptomatic VTE and bleeding in patients with a first episode of idiopathic VTE

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Trial design

Randomized, double-blind study
Active treatment: continuation of warfarin therapy (target INR 2.0–3.0) for a further 24 months (n=79)
Control treatment: placebo (n=83) 

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Primary efficacy endpoint: symptomatic, objectively confirmed recurrence of VTE
Primary safety endpoints: major and minor bleeding, all-cause death

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Trial participants

162 consecutive patients (mean age 59 years) with a first episode of idiopathic VTE who had completed 3 uninterrupted months of oral anticoagulant treatment after an initial course of treatment with UFH or LMWH

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Efficacy outcome: Of the 79 patients assigned to continue warfarin, one had a confirmed episode of recurrent VTE (1.3% per patient-year), as compared with 17 of 83 patients given placebo (27.4% per patient-year). This resulted in a relative risk reduction of 95%. All episodes of recurrent VTE were idiopathic
Safety outcome: Major bleeding occurred in 3 patients assigned to warfarin (3.8% per patient-year) and no such episodes among those receiving placebo. Minor bleeding occurred in 7.7% and 1.4% per patient-years, respectively. One patient in the warfarin group and 3 patients in the placebo group died during the study (1.2% vs. 4.1% per patient-year)

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Efficacy: The clinical benefit achieved during the additional 24 months of oral anticoagulant therapy was significant. Therefore patients with a first episode of idiopathic VTE should be treated with anticoagulants for longer than 3 months
Safety: Extended warfarin therapy was associated with a risk of major bleeding of about 3% per year

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Kearon C, Gent M, Hirsh J, Weitz J, Kovacs MJ, Anderson DR, Turpie AG, Green D, Ginsberg JS, Wells P, MacKinnon B, Julian JA. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901-907

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Corresponding author

Clive Kearon, MD, Hamilton Health Sciences Corporation, Henderson Division, 711 Concession St., Hamilton, ON L8V 1C3, Canada

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