Venous thromboembolism: LMWH long term is probably as safe as vitamin K antagonists

Clinical bottom line (level 1a)

  1. Patients with a symptomatic venous thromboembolism who take low molecular weight heparin long term compared with vitamin K antagonists are not clearly more likely to die, have a major bleed or a recurrent episode at 3 or 12 months.
van der Heijden et al: Cochrane Library 2000; 4 : -
Expires October 2003

The study

Systematic review of all randomised controlled tials of
  • Patients: symptomatic venous thromboembolism (diagnosed objectively)
  • Intervention: long-term low molecular weight heparin: enoxaparin, dalteparin, nadroparin once daily compared with vitamin K antagonists
  • Outcome: symptomatic venous thromboembolism, bleeding

    Articles found in Medline, Embase, Current Contents using ?English, 1966 to 1999 (search terms: ) and hand-searching relevant journals; communicating with colleagues and contacting pharmaceutical companies

    Selection criteria: see above
    Appraisal criteria: detailed in text
    Articles excluded if: no acceptable objective test used

    5 studies found involving 850 patients receiving 3 months of treatment with up to 9 months follow-up
    The studies' outcomes were not found to be heterogeneous.

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NN T
    (95% CI)
    recurrent venous thromboembolism 3 months 34/442
    (7.7%)    		 0.72
    (0.42 to 1.23)     		-49
    (NNT = 62 to infinity;
    NNH = 23 to infinity)
    recurrent venous thromboembolism 12 months 41/387
    (10.6%)    		 0.92
    (0.57 to 1.47)     		-130
    (NNT = 24 to infinity;
    NNH = 23 to infinity)
    major bleeding 3 months 8/442
    (1.8%)    		 0.63
    (0.21 to 1.88)     		-15
    (NNT = 65 to infinity;
    NNH = 70 to infinity)
    death 3 months 10/442
    (2.3%)    		 350
    (-84 to 28)     		1.13
    (NNT = 28 to infinity;
    NNH = 84 to infinity)
    death 12 months 18/387
    (4.7%)    		 1.30
    (0.69 to 2.44)     		76
    (NNT = 17 to infinity;
    NNH = 72 to infinity)

    Comments

    1. Patients initially received unfractionated heparin or LMWH for 7 to 10 days before randomisation.

    Citation

    1. van der Heijden JF, Hutten BA, Buller HR, et al: Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism. Cochrane Library 2000; 4 : -
    Search Terms: hepar* in Cochrane
    Contributor: Chris Ball, October 2001
    Reviewer:

    Clinical Question.
    Patient symptomatic venous thromboembolism
    Intervention or Exposure long-term low molecular weight heparin
    Comparison vitamin K antagonists; warfarin, acenocoumarol
    Outcome death, major bleed, recurrent venous thromboembolism
    		•