Warfarin Optimal Duration Italian Trial in patients with Deep Vein Thrombosis (2001)


Long-term prevention of recurrent idiopathic DVT

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To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 1 year in patients with a first episode of idiopathic proximal DVT

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Trial design

Randomized, open study with parallel groups
Active treatment: continuation of warfarin or acenocoumarol (target INR 2.0–3.0) for a further 9 months (n=134)
Control treatment: discontinuation of anticoagulant therapy (n=133)

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Primary efficacy endpoint: symptomatic, objectively confirmed recurrence of VTE during at least 2 years of follow-up
Primary safety endpoints: major bleeding, all-cause death

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Trial participants

267 patients, aged 15–85 years, with a first episode of idiopathic proximal DVT who had completed 3 uninterrupted months of oral anticoagulant therapy without a recurrence or bleeding

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Efficacy outcome: In the intention-to-treat analysis, 21 of the 34 patients assigned to continue therapy (15.7%) and 21 of the 133 patients assigned to discontinue therapy (15.8%) had recurrent VTE. All episodes of recurrent VTE were idiopathic, and none were fatal. The average time to recurrence was 16.0 months from randomization in the patients assigned to continue therapy and 11.2 months from randomization in those assigned to discontinue therapy. The risk of recurrence during the first 9 months of follow-up was lower among the patients assigned to continue therapy (1 patient, 1.2% per patient-year) than in those assigned to discontinue therapy (11 patients, 12.3% per patient-year). After 9 months the corresponding rates were 5.1% and 5.0% per patient-year
Safety outcome: Major bleeding occurred in 3.0% of patients in the continuation group and in 1.5% in the discontinuation group. 5.2% and 5.3% of the patients died

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Efficacy: The clinical benefit achieved during the additional 9 months of oral anticoagulant therapy was not maintained after the discontinuation of therapy. Therefore recurrences of idiopathic DVT could be prevented only by continuous anticoagulation of indefinite duration
Safety: The incidence of adverse events (major bleeding, all-cause death) was similar in both groups

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Agnelli G, Prandoni P, Santamaria MG, Bagatella P, Iorio A, Bazzan M, Moia M, Guazzaloca G, Bertoldi A, Tomasi C, Scannapieco G, Ageno W, and the Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. N Engl J Med 2001;345:165-169

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Corresponding author

Prof. Giancarlo Agnelli, MD, Sezione di Medicina Interna e Cardiovascolare, Dipartimento di Medicina Interna, Università di Perugia, Via Enrico dal Pozzo, 06123 Perugia, Italy, e-mail: agnellig@unipg.it.

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