WODIT PE

Warfarin Optimal Duration Italian Trial in patients with Pulmonary Embolism (2003)

Condition

Long-term prevention of recurrent VTE after a first episode of PE

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Objective

To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 6 months in patients with a first episode of PE associated with temporary risk factors or to 1 year in patients with idiopathic PE

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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 3 additional months in patients with a first episode of PE and transient risk factors (n=75) or for 9 additional months in patients with idiopathic PE (n=90)
Control treatment: discontinuation of anticoagulant therapy (patients with PE and transient risk factors, n=70; patients with idiopathic PE, n=91)

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Endpoints

Primary efficacy endpoint: recurrence of symptomatic, objectively confirmed VTE after the initial 3 months of anticoagulation
Primary safety endpoints: cumulative incidence of adverse outcome events (recurrence of VTE, death, or major bleeding)

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Trial participants

326 patients, aged 15–85 years, with a first episode of symptomatic, confirmed PE who had completed 3 uninterrupted months of oral anticoagulant therapy without a recurrence or bleeding. Patients were categorized as having idiopathic PE or PE associated with transient risk factors (e.g. recent trauma, surgery, prolonged immobilization)

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Results

Efficacy outcome: Recurrent VTE occurred in 9.1% (15/165) of patients in the continuation group and in 11.2% (18/161) of patients in the discontinuation group. In patients with idiopathic PE, the incidence of recurrence was 12.2% in the continuation group and 12.1% in the discontinuation group. In patients with PE associated with transient risk factors, the rates were 5.3% and 10.0%, respectively. All but one of the recurrences occurred after anticoagulant treatment was discontinued. After treatment discontinuation, the incidence of recurrence was 5.6% in both treatment groups during the first year and 3.9% and 3.5% during the second year in patients assigned to continue and discontinue treatment, respectively.
Safety outcome: The cumulative incidence of VTE recurrence, death, or major bleeding was 16.5% in patients in the continuation group and 14.9% in patients in the discontinuation group. Major bleeding occurred in 3 patients assigned to continue anticoagulation and in one patient assigned to discontinue anticoagulation. The mortality rates were 7.5% and 4.2%, respectively

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Summary

Efficacy: The clinical benefit during the 3 or 9 additional months of anticoagulation was not maintained after treatment was discontinued. Therefore patients with PE are potential candidates for indefinite oral anticoagulant therapy
Safety: During extended anticoagulation, the incidence of major bleeding was low

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Reference

Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, Imberti D, Poggio R, Ageno W, Pogliani E, Porro F, Zonzin P, for the Warfarin Optimal Duration Italian Trial Investigators. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003;139:19-25

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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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