Deep vein thrombosis: three months anticoagulation was not clearly better than four weeks

Clinical bottom line (level 1b-)

  1. In patients with proximal deep vein thrombosis, three months of anticoagulation with warfarin was not clearly better than four weeks.
Levine et al: Thrombosis and Haemostasis 1995; 74 (2): 606-611
Expires May 2003

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: two university hospitals, Canada

214 patients (aged mean 63 years, 55% male) venographically proven proximal deep venous thrombosis

Excluded if
  • two or more previous episodes of venous thromboembolism or DVT
  • thrombophilia
  • active bleeding
  • peptic ulcer disease
  • requiring continuing warfarin (eg. heart valve)
  • geographically inaccessible
  • life expectancy <3 months
  • psychiatric/affective disorder
  • pregnant


    • Control Group: (n = 105, 104 analysed): 4 weeks warfarin
    Experimental Group: (n = 109, 103 analysed): 12 weeks warfarin
    All patients had heparin 5000 units iv bolus loading dose and 30,000 units per 24 hours, adjusted to a aPTT of 1.9 to 2.7. Patients started warfarin on day five, adjusted so INR was 2.0 to 3.0. All patients had impedance plethysmography at four weeks, and, if normal, patients were randomised.
    97% followed for 11 months
    Outcome notes:
    • recurrent DVT : diagnosed by positive IPG, confirmed by venogram
    • major bleed : fall in haemoglobin >2 g/dl, or two or more units transfused or retroperitoneal or intracranial bleed

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent DVT 11 months 12
    (12%)    		 7
    (6.8%)    		 41%
    (-44% to 76%)    		 4.74%
    (-3.09% to 12.6%)    		 21
    (NNT = 8 to infinity;
    NNH = 32 to infinity)
    major bleed 8 weeks 0
    (0%)    		 1
    (0.97%)    		 %
    (% to %)    		 -0.97%
    (-2.86% to 0.92%)    		 -103
    (NNT = 108 to infinity;
    NNH = 35 to infinity)
    death 11 months 9
    (8.65%)    		 9
    (8.74%)    		 -1%
    (-140% to 58%)    		 -0.08%
    (-7.76% to 7.59%)    		 -1200
    (NNT = 13 to infinity;
    NNH = 13 to infinity)

    Comments

    1. The study was not large enough to show whether four weeks of warfarin is as effective and safe as three months.
    2. No patients with transient risk factors on three months of warfarin had a recurrent venous thromboembolic event.

    Citation

    1. Levine MN, Hirsh J, Gent M, et al: Optimal duration of oral anticoagulation treatment: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thrombosis and Haemostasis 1995; 74 (2): 606-611
    Contributor: Chris Ball and Clare Wotton, May 2000
    Reviewer:

    Clinical Question.
    Patient DVT
    Intervention or Exposure 12 weeks warfarin
    Comparison 4 weeks warfarin
    Outcome recurrent DVT