Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2019 Jul;104(7):1493-1501.
doi: 10.3324/haematol.2018.210971. Epub 2019 Jan 3.

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

Francis Couturaud  1 , Gilles Pernod  2 , Emilie Presles  3 , Elisabeth Duhamel  4 , Patrick Jego  5 , Karine Provost  6 , Brigitte Pan-Petesch  7 , Claire Bal Dit Sollier  8 , Cécile Tromeur  9 , Clément Hoffmann  10 , Luc Bressollette  10 , Philippe Lorillon  11 , Philippe Girard  12 , Emmanuelle Le Moigne  9 , Aurelia Le Hir  9 , Marie Guégan  9 , Silvy Laporte  3 , Patrick Mismetti  13 , Karine Lacut  9 , Jean-Luc Bosson  14 , Laurent Bertoletti  13 , Oliver Sanchez  14 , Guy Meyer  14 , Christophe Leroyer  9 , Dominique Mottier  9 ; “PADIS-DVT” investigators
Affiliations
Randomized Controlled Trial

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

Francis Couturaud et al. Haematologica. 2019 Jul.

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Patients’ flow through the study.
Figure 2.
Figure 2.
Kaplan-Meier estimates of the probability of the composite outcome of recurrent venous thromboembolism and major bleeding during the entire study period, according to study group. The unadjusted hazard ratios (95% confidence interval) warfarin/placebo were 0.03 (0.01 to 0.51) during the treatment period and 0.72 (0.35 to 1.46) during the entire study period.
Figure 3.
Figure 3.
Meta-analysis of the PADIS-PE and PADIS-DVT studies. Pooled hazard ratios were calculated for the composite of recurrent venous thromboembolism and major bleeding and for the recurrent venous thromboembolism component. The pooled hazard ratio for the component of major bleeding is not reported as there was no major bleeding in the placebo group of the PADIS-DVT trial. HR: hazard ratio; 95% CI: 95% confidence interval; PE: pulmonary embolism; DVT: deep-vein thrombosis.
See this image and copyright information in PMC

References

    1. Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism. Lancet. 1992;340(8824): 873–876. - PubMed
    1. Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep-vein thrombosis. Thromb Haemost. 1995;74(2):606–611. - PubMed
    1. Schulman S, Rhedin A-S, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med. 1995;332(25):1661–1665. - PubMed
    1. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999;340(12):901-907. Erratum in: N Engl J Med. 1999;341(4):298. - PubMed
    1. Agnelli G, Prandoni P, Santamaria MG, et al. Warfarin Optimal Duration Italian Trial Investigators. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med. 2001;345(3):165–169. - PubMed

Publication types

Associated data