Six months versus two years of oral anticoagulation after a first episode of unprovoked deep-vein thrombosis. The PADIS-DVT randomized clinical trial.

Abstract

The optimal duration of anticoagulation after a first episode of unprovoked deep-vein thrombosis is uncertain. We aimed to assess the benefits and risks of an additional 18 months of treatment with warfarin versus placebo, after an initial 6 months of anticoagulation for a first unprovoked proximal deep-vein thrombosis. We conducted a multicenter, randomized, double-blind, controlled trial comparing an additional 18 months of warfarin with placebo in patients with a unprovoked proximal deep-vein thrombosis initially treated for 6 months (treatment period: 18 months; follow up after treatment period: 24 months). The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months. Secondary outcomes were the composite at 42 months, as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. All outcomes were centrally adjudicated. A total of 104 patients, enrolled between July 2007 and October 2013 were analyzed on an intention-to-treat basis; no patient was lost to follow-up. During the 18-month treatment period, the primary outcome occurred in none of the 50 patients in the warfarin group and in 16 out of 54 patients (cumulative risk, 29.6%) in the placebo group (hazard ratio, 0.03; 95% confidence interval: 0.01 to 0.09; P<0.001). During the entire 42-month study period, the composite outcome occurred in 14 patients (cumulative risk, 36.8%) in the warfarin group and 17 patients (cumulative risk, 31.5%) in the placebo group (hazard ratio, 0.72; 95% confidence interval: 0.35-1.46). In conclusion, after a first unprovoked proximal deep-vein thrombosis initially treated for 6 months, an additional 18 months of warfarin therapy reduced the composite of recurrent venous thrombosis and major bleeding compared to placebo. However, this benefit was not maintained after stopping anticoagulation. Clinical registration: this trial was registered at www.clinicaltrials.gov as #NCT00740493.

• Authors: Francis Couturaud, Gilles Pernod, Emilie Presles, Elisabeth Duhamel, Patrick Jego, Karine Provost, Brigitte Pan-Petesch, Claire Bal Dit Sollier, Cécile Tromeur, Clément Hoffmann, Luc Bressollette, Philippe Lorillon, Philippe Girard, Emmanuelle Le Moigne, Aurelia Le Hir, Marie Guégan, Silvy Laporte, Patrick Mismetti, Karine Lacut, Jean-Luc Bosson, Laurent Bertoletti, Oliver Sanchez, Guy Meyer, Christophe Leroyer, Dominique Mottier, “PADIS-DVT” investigators
• Journal: Haematologica (Haematologica) Vol. 104 Issue 7 Pg. 1493-1501 (07 2019) ISSN: 1592-8721 [Electronic] Italy
• PMID: 30606789 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2019 Ferrata Storti Foundation.

Chemical References

• Anticoagulants
• Warfarin

Topics

• Administration, Oral
• Aged
• Anticoagulants (administration & dosage)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Prognosis
• Time Factors
• Venous Thrombosis (drug therapy, pathology)
• Warfarin (administration & dosage)
• Withholding Treatment (statistics & numerical data)