Pulmonary embolism: LMWH was probably as good as heparin.

Clinical bottom line (level 1b-)

  1. Patients with pulmonary embolism treated with tinzaparin or iv heparin had no significant differences in the rate of recurrent venous thromboembolism, major bleed, thrombocytopenia or death.
Simonneau et al: New England Journal of Medicine 1997; 337 (10): 663-669
Expires September 2003

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: 57 centres in France, Belgium, Switzerland

612 patients (aged mean 67 years, 56% female) clinically suspected pulmonary embolism, diagnosed by pulmonary angiogram or high probability ventilation-perfusion scan, or if indeterminate accompanied by a DVT detected by ultrasound or venography

Excluded if
  • <19 years old
  • thought to have massive PE requiring thrombolysis or embolectomy
  • received anticoagulation treatment for > 24 hours at therapeutic doses
  • if life expectancy < three months
  • severe hepatic or renal failure
  • pregnant
  • non-compliance thought likely
  • active bleeding or disorders contraindicating anticoagulation treatment


    • Control Group: (n = 308, 308 analysed): heparin intravenous 50 units/kg bolus then 500 units/ kg/ day infusion. Adjusted so that aPTT 2.0-3.0. Checked 6 hours after start or any change and then daily.
    Experimental Group: (n = 304, 304 analysed): tinzaparin 175 units/ kg subcutaneously once daily
    All patients had anticoagulation begun on day 1-3. Adjusted so INR 2.0-3.0. Heparin or LMWH continued until INR > 2.0 for two days following at least five days of heparin. All patients had repeated perfusion scans on day 8-11
    100% followed for 90 days
    Outcome notes:
    • recurrent venous thromboembolism: : recurrent PE diagnosed by clinical findings and v/q scan with new perfusion defect (segmental or larger) or pulmonary angiogram with new defect; recurrent DVT diagnosed by clinical findings and ultrasound or venogram depending on prior examination performed. Studies assessed by three blinded observers.

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    death 90 days 14
    (4.55%)    		 12
    (3.95%)    		 13%
    (-85% to 59%)    		 0.60%
    (-2.60% to 3.79%)    		 170
    (NNT = 26 to infinity;
    NNH = 39 to infinity)
    recurrent venous thromboembolism: 90 days 6
    (1.95%)    		 5
    (1.64%)    		 16%
    (-174% to 74%)    		 0.30%
    (-1.80% to 2.41%)    		 330
    (NNT = 42 to infinity;
    NNH = 56 to infinity)
    major bleed 90 days 8
    (2.60%)    		 6
    (1.97%)    		 24%
    (-116% to 73%)    		 0.62%
    (-1.74% to 2.99%)    		 160
    (NNT = 33 to infinity;
    NNH = 57 to infinity)
    thrombocytopenia 90 days 1
    (0.32%)    		 0
    (0.00%)    		 100%
    (% to %)    		 0.32%
    (-0.31% to 0.96%)    		 310
    (NNT = 100 to infinity;
    NNH = 320 to infinity)

    Comments

    1. Patients excluded who might have shown benefit form LMWH. Unclear how the physicians decided which patients need thrombolysis or embolectomy. N.B. there is no good evidence to show either treatment alters survival.
    2. The trial may not have been large enough to show small differences between treatments. If both treatments are as effective - which is more cost-effective?

    Citation

    1. Simonneau G, Sors H, Charbonnier B, et al: A comparison of low-molecular-weight heparin and unfractionated heparin for acute pulmonary embolism. New England Journal of Medicine 1997; 337 (10): 663-669
    Contributor: Chris Ball and Clare Wotton, Unknown Month 2000
    Reviewer:

    Clinical Question.
    Patient pulmonary embolism
    Intervention or Exposure tinzaparin
    Comparison iv heparin
    Outcome venous thromboembolism, major bleed, death