Deep vein thrombosis: heparin and warfarin is more effective than warfarin alone.

Clinical bottom line (level 1b)

  1. In patients with proximal deep vein thrombosis, giveing heparin while awaiting satisfactory oral anticoagulation reduces symptomatic DVT recurrence (NNT = 8 at 6 months) .
  2. The effect on major bleeding is unclear.
Brandjes et al: New England Journal of Medicine 1992; 327 (21): 1485-1489
Expires May 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: acute hospital, Holland

120 patients (aged mean 57 years, 54% female) proximal deep vein thrombosis, diagnosed by venogram

Excluded if
  • previously diagnosed DVT
  • clinically suspected pulmonary embolism, bilateral venous thrombus or plegmasia when referred
  • received anticoagulation
  • pregnant
  • <18 or >85 years old
  • life expectancy of <6 months
  • coagulation-inhibitor deficiency
  • refused consent


    • Control Group: (n = 60, 60 analysed): heparin iv 5000 units bolus dose, then 1250 units per hour for seven days, plus acenocoumarol 6 mg on first day, then 4 mg on second day, then titred so that INR 2.0-3.0- continued for 12 weeks
    Experimental Group: (n = 60, 60 analysed): acenocoumarol alone

    100% followed for 6 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNH
    (95% CI)
    symptomatic recurrence 6 months 4
    (6.67%)    		 12
    (20.0%)    		 -200%
    (-780% to -3%)    		 -13.3%
    (-25.3% to -1.41%)    		 8
    (4 to 71)
    major bleed 6 months 2
    (3.33%)    		 3
    (5.00%)    		 -50%
    (-770% to 74%)    		 -1.67%
    (-8.81% to 5.48%)    		 60
    (NNT = 18 to infinity;
    NNH = 11 to infinity)

    Comments

    1. 78% of patients had a recognisable cause.

    Citation

    1. Brandjes DPM, Heijboer H, Buller HR, et al: Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. New England Journal of Medicine 1992; 327 (21): 1485-1489
    Contributor: Bob Phillips, Chris Ball and Clare Wotton, May 2000
    Reviewer: James Douketis

    Clinical Question.
    Patient proximal DVT
    Intervention or Exposure heparin plus acenocoumarol / warfarin
    Comparison acenocoumarol / warfarin
    Outcome recurrence