Deep vein thrombosis: LMWH was safe and effective in outpatients.

Clinical bottom line (level 1b-)

  1. Patients with acute proximal deep vein thrombosis who were given LMWH primarily at home had no clear difference in recurrent thromboembolism, major bleed or death than those given standard heparin.
  2. Patients given LMWH spent about 5 days less in hospital than those given standard heparin.
Levine et al: New England Journal of Medicine 1996; 334 (11): 677-681
Expires December 2003

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: multicentre, Canada

500 patients (aged mean 58 years, 60% male) acute proximal deep vein thrombosis confirmed by either venography or duplex ultrasonography

Excluded if
  • two or more previous episodes of DVT or PE
  • currently active bleeding, active peptic ulcer disease, or a familial bleeding disorder
  • concurrent symptomatic PE
  • treatment lasting >48 hours with standard heparin for DVT
  • inability to be treated with LMWH as an outpatient because of coexisting condition
  • likelihood of noncompliance
  • inability to perform follow-up
  • presence of known deficiency of antithrombin III, protein G or protein S
  • pregnancy


    • Note:
  • Patients were stratified according to centre, mode of diagnosis and category of patient (outpatients, with DVT admitted at night or on a weekend, hospitalised for other reasons and had DVT diagnosed subsequently)


    • Control Group: (n = 253, 253 analysed): continuous iv standard heparin and admitted to hospital. Bolus dose of 5000 units iv, followed by a continuous infusion of 20, 000 units in 500 ml of 5% dextrose solution, with 32 ml administered per hour
    Experimental Group: (n = 247, 247 analysed): enoxaparin , primarily given at home. 1 mg/ kg body weight sc twice daily
    Dose was adjusted to maintain the aPTT between 60 to 85 seconds. Patients began warfarin on the evening of the second day- first dose 10 mg, and INR was maintained at 2.0 to 3.0.
    100% followed for 3 months
    Outcome notes:
    • major bleed : overt and associated with either a decrease in haemoglobin level of at least 2.0 g per decilitre or a need for transfusion of two or more units of blood, or if it was retroperitoneal or intracranial

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    symptomatic recurrent thromboembolism 3 months 17
    (6.72%)    		 13
    (5.26%)    		 22%
    (-58% to 61%)    		 1.46%
    (-2.70% to 5.61%)    		 69
    (NNT = 18 to infinity;
    NNH = 37 to infinity)
    major bleed 48 hours 3
    (1.19%)    		 5
    (2.02%)    		 -71%
    (-607% to 59%)    		 -0.84%
    (-3.04% to 1.37%)    		 -120
    (NNT = 73 to infinity;
    NNH = 33 to infinity)
    death 3 months 17
    (6.72%)    		 11
    (4.45%)    		 34%
    (-39% to 68%)    		 2.27%
    (-1.75% to 6.28%)    		 44
    (NNT = 16 to infinity;
    NNH = 57 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    mean time spent in hospital 6.5
    (3.4)     		1.1
    (2.9)     		-5.4
    (-6.0 to -4.8)

    Citation

    1. Levine M, Gent M, Hirsh J, et al: A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. New England Journal of Medicine 1996; 334 (11): 677-681
    Contributor: Clare Wotton, December 2000
    Reviewer:

    Clinical Question.
    Patient DVT
    Intervention or Exposure LMWH
    Comparison standard heparin
    Outcome hospitalisation, major bleed