Venous thromboembolism: LMWH was probably as good as heparin.

Clinical bottom line (level 1b-)

  1. Patients with venous thromboembolism treated with reviparin or iv heparin had no significant difference in the rate of recurrent venous thromboembolism, death or major bleeding.
The Columbus investigators : New England Journal of Medicine 1997; 337 (10): 657-662
Expires September 2003

The study

Single-blinded concealed randomised trial with intention-to-treat
Setting: ~30 centres in Europe, Canada, Australia

1021 patients (aged mean 60 years, 51% male) acute symptomatic deep vein thrombosis or pulmonary embolism. (DVT diagnosed by ultrasound of venogram: included calf DVT; PE diagnosed by high-probability v/q scan or pulmonary angiogram. If v/q scan was non-diagnostic, DVT looked for using compressive ultrasound or venography)

Excluded if
  • had therapeutic doses of LMWH or oral anticoagulation > 24 hours
  • anticoagulation contraindicated
  • thrombolytic treatment planned
  • GI bleed in last 14 days
  • difficult to follow-up
  • pregnant or child-bearing potential using no contraception
  • platelets < 100
  • < 35 kg
  • <18 years old
  • stroke in last ten days
  • surgery with anaesthesia in last three days


    • Control Group: (n = 511, 511 analysed): intravenous heparin bolus of 5000 units, followed by iv infusion of 1250 units / hour with 1PTT 1.5-2.5. aPTT checked after 6-12 hours after start and following changes, then daily
    Experimental Group: (n = 510, 510 analysed): reviparin subcutaneously twice daily: 6300 units > 60 kg, 4200 units 46-60 kg, 3500 units 35-45 kg
    All patients started coumarin on day 1 or 2 for twelve weeks: therapeutic range INR 2.0-3.0. Study drug stopped if INR > 2.0 for 2 days.
    100% followed for 12 weeks
    Outcome notes:
    • recurrent venous thromboembolism : recurrent DVT: increased pain or swelling and intraluminal filling defect on venogram (new of extension of non-visualised proximal veins) or abnormal USS in area that had previously been normal, or abnormal impedance plethysmography; recurrent PE: chest pain or dyspnoea and new intraluminal defect or sudden vessel cut-off > 2.55mm diameter on pulmonary angiogram, or 75% probability on V/Q scan, or autopsy, or none of the above but proven DVT
    • major bleed : clinically overt and any of: fall in haemoglobin of 2+ g/dl; transfused 2+ units; retroperitoneal or intracranial bleed; permanent treatment discontinued

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent venous thromboembolism 12 weeks 25
    (4.89%)    		 27
    (5.29%)    		 -8%
    (-84% to 36%)    		 -0.40%
    (-3.10% to 2.30%)    		 -250
    (NNT = 44 to infinity;
    NNH = 32 to infinity)
    major bleed 12 weeks 12
    (2.35%)    		 16
    (3.14%)    		 -34%
    (-180% to 36%)    		 -0.79%
    (-2.79% to 1.21%)    		 -130
    (NNT = 82 to infinity;
    NNH = 36 to infinity)
    death 12 weeks 39
    (7.63%)    		 36
    (7.06%)    		 8%
    (-43% to 40%)    		 0.57%
    (-2.63% to 3.77%)    		 170
    (NNT = 27 to infinity;
    NNH = 38 to infinity)

  • No significant difference in recurrence rate for patients who had PE (16/271= 5.9%) or DVT (36/750 = 4.8%) ~60% (31/52) of recurrences occurred within the first 14 days.

    • Comments

    1. Differences between heparin and LMWH are probably small - the study may have missed small differences even though it was quite a large study.

    Citation

    1. The Columbus investigators , : low-molecular-weight heparin in the treatment of patients with venous thromboembolism. New England Journal of Medicine 1997; 337 (10): 657-662
    Contributor: Chris Ball and Clare Wotton, Unknown Month 2000
    Reviewer:

    Clinical Question.
    Patient venous thromboembolism
    Intervention or Exposure reviparin
    Comparison iv heparin
    Outcome recurrence, death, major bleeding