Venous thromboembolism prophylaxis: heparin reduced VTE in non-surgical patients.

Clinical bottom line (level 1b)

  1. In older patients admitted to hospital with infection, 3 weeks of heparin prophylaxis reduced venous thromboembolism (NNT = 125 at 60 days) .
  2. There is no clear effect on death, fatal pulmonary embolism and bleeding at 2 months.
  3. Very few necropsy-identified PE were suspected before death
Gardlund : Lancet 1996; 347: 1357-1361
Expires May 2003

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: six infection wards, Sweden

11693 patients (aged mean 75 years, ?% male) infection (pneumonia, liver disease, skin/soft tissue infection, urinary infection, gastroenteritis)

Excluded if
  • <55 years old
  • on pre-existing anticoagulation
  • readmitted subsequently within 60 days
  • mobile
  • persistent haemorrhage or increased bleeding risk (clotting disorder, plt<70, intraocular bleed)
  • heparin prophylaxis already decided by attending clinician
  • liver or renal failure
  • HIV positive
  • terminal disease


    • Control Group: (n = 5917, 5917 analysed): no prophylaxis
    Experimental Group: (n = 5776, 5776 analysed): heparin 5000 units twice daily until discharged, or for 21 days

    100% followed for 60 days

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    non-fatal venous thromboembolism 60 days 118
    (1.99%)    		 69
    (1.19%)    		 40%
    (20% to 55%)    		 0.80%
    (0.35% to 1.25%)    		 125
    (80 to 289)
    death 60 days 333
    (5.63%)    		 304
    (5.26%)    		 6%
    (-9% to 20%)    		 0.36%
    (-0.46% to 1.19%)    		 274
    (NNT = 84 to infinity;
    NNH = 218 to infinity)
    venous thromboembolism at autopsy 60 days 95
    (1.61%)    		 92
    (1.59%)    		 1%
    (-32% to 25%)    		 0.01%
    (-0.44% to 0.47%)    		 7800
    (NNT = 214 to infinity;
    NNH = 226 to infinity)
    fatal pulmonary embolism 60 days 16
    (0.27%)    		 15
    (0.26%)    		 4%
    (-94% to 52%)    		 0.01%
    (-0.18% to 0.20%)    		 9300
    (NNT = 510 to infinity;
    NNH = 570 to infinity)
    serious bleed 60 days 14
    (0.24%)    		 6
    (0.10%)    		 56%
    (-14% to 83%)    		 0.13%
    (-0.02% to 0.28%)    		 750
    (NNT = 360 to infinity;
    NNH = 6100 to infinity)

  • 25/31 (80%) of patients with fatal PE were bed-bound

    • Comments

    1. Patients were asked for their participation in the study only if randomised tot the heparin arm
    2. Little information was given about the patients or the severity of their infections- list of infections suggests a very broad range of conditions.
    3. No information was given on how non-fatal venous thromboembolism was diagnosed.
    4. Autopsies occurred in only 60% of patients.
    5. Therefore, results must be treated with caution- specific high risk medical patients may benefit.

    Citation

    1. Gardlund B, : Randomised, controlled trial of low-dose heparin for the prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet 1996; 347: 1357-1361
    Contributor: Chris Ball and Clare Wotton, May 2000
    Reviewer: Alex Gallus

    Clinical Question.
    Patient infection
    Intervention or Exposure heparin
    Comparison no prophylaxis
    Outcome venous thromboembolism