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Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial.

Francis Couturaud 1, 2, 3, * Olivier Sanchez 4, 1, 5 Gilles Pernod 1, 6 Patrick Mismetti 7, 8 Patrick Jego 9, 1 Elisabeth Duhamel 10 Karine Provost Claire Bal Dit Sollier Emilie Presles Philippe Castellant 11 Florence Parent 12 Pierre-Yves Salaun 3 Luc Bressollette 2, 3 Michel Nonent 3, 13 Philippe Lorillon Philippe Girard 1, 14 Karine Lacut 15, 3 Marie Guégan 15 Jean-Luc Bosson 16 Silvy Laporte 17 Christophe Leroyer 2, 3 Hervé Décousus 8, 7 Guy Meyer 5, 4, 1 Dominique Mottier 15, 2, 3 
Abstract : The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain. To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist. Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers. Warfarin or placebo for 18 months. The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups. Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy. Identifier: NCT00740883.
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Submitted on : Wednesday, January 20, 2016 - 3:54:57 PM
Last modification on : Thursday, October 13, 2022 - 3:06:39 PM

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Francis Couturaud, Olivier Sanchez, Gilles Pernod, Patrick Mismetti, Patrick Jego, et al.. Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial.. Journal of the American Medical Association, 2015, 314 (1), pp.31-40. ⟨10.1001/jama.2015.7046⟩. ⟨hal-01259554⟩



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