Venous thromboembolism: fewer deaths and bleeds on LMWH compared with heparin.

Clinical bottom line (level 1a)

  1. Patients with venous thromboembolism who have low molecular weight heparin compared with unfractionated heparin, are less likely to die (NNT = 59 at 6 months) and less likely to have a major bleed (NNT = 115 at 6 months) .
  2. Patients on LMWH have a greater decrease in thrombus size (NNT = 10 at 6 months) .
  3. There is no clear difference in VTE recurrence, but there is a trend towards a decrease with LMWH.
  4. Patients with cancer are much less likely to die if given LMWH (NNT = 10 at 6 months) .
van den Belt et al: The Cochrane Library, Issue 3, Oxford: Update Software 1999; 3: -
Expires May 2003

The study

Systematic review of randomised controlled trials of
  • Patients: acute deep venous thrombosis or pulmonary embolism
  • Intervention: fixed-dose subcutaneous low molecular weight heparins compared with adjusted dose intravenous or subcutaneous unfractionated heparin
  • Outcome: recurrent venous thromboembolism, major bleed, mortality, reduction in thrombus size


    • Articles found in all using MEDLINE, EMBASE, Lilacs, up to 1998 (search terms: detailed in text ) and hand searching relevant journals, contacting colleagues and pharmaceutical companies for unpublished trials

    Selection criteria: as above
    Appraisal criteria: detailed in text
    Articles excluded if:

    Thirteen trials involving 4354 patients were found. Six LMWHs were used- nadroparin, tinzaparin, enoxaparin, dalteparin, CY222, reviparin
    Trials were not significantly heterogeneous.

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    recurrent VTE 3-6 months 44/1798
    (2.45%)    		 0.75
    (0.48 to 1.18)     		166
    (NNT = 79 to infinity;
    NNH = 233 to infinity)
    pulmonary embolism 3-6 months 44/411
    (10.7%)    		 0.91
    (0.42 to 1.97)     		115
    (NNT = 17 to infinity;
    NNH = 12 to infinity)
    major bleed 3-6 months 43/2196
    (1.96%)    		 0.55
    (0.34 to 0.89)     		115
    (78 to 472)
    death 3-6 months 125/1816
    (6.88%)    		 0.74
    (0.57 to 0.98)     		59
    (35 to 780)
    mortality in patients with cancer 3-6 months 54/225
    (24.0%)    		 0.53
    (0.33 to 0.85)     		10
    (7 to 35)
    mortality in patients without cancer 3-6 months 36/1073
    (3.36%)    		 0.97
    (0.61 to 1.56)     		1000
    (NNT = 78 to infinity;
    NNH = 56 to infinity)
    venographic reduction in thrombus size 3-6 months 239/504
    (47.4%)    		 0.67
    (0.52 to 0.86)     		10
    (6 to 27)

    Comments

    1. Recurrent venous thromboembolism was objectively documented.
    2. Differences in LMWH have not been proven to have clinical significance.
    3. Dose schedules at extremes of BMI or in renal insufficiency are still poorly investigated.

    Citation

    1. van den Belt AGM, Prims MH, Lensing AWA, et al: Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism (Cochrane Review). The Cochrane Library, Issue 3, Oxford: Update Software 1999; 3: -
    Search Terms: venous thromboembolism in Cochrane
    Contributor: Chris Ball and Clare Wotton, May 2000
    Reviewer: Deepak L Bhatt

    Clinical Question.
    Patient DVT or PE
    Intervention or Exposure LMWH
    Comparison unfractionated heparin
    Outcome recurrent VTE