Anticoagulation (long term): subcutaneous heparin reduced bleeds.

Clinical bottom line (level 1b)

  1. In patients with deep vein thrombosis, subcutaneous heparin was probably as effective as warfarin for long-term anticoagulation.
  2. The risk of any bleeding was reduced with subcutaneous heparin (NNT = 7 at 12 weeks) .
Hull et al: New England Journal of Medicine 1982; 306 (4): 189-194
Expires June 2003

The study

Unblinded concealed randomised trial without intention-to-treat
Setting: university hospital, Canada

106 patients (aged ?, 50% male) proximal deep vein thrombosis diagnosed by venogram

Excluded if
  • pregnant
  • active peptic ulcer disease
  • contrast media allergy
  • geographically inaccessible


    • Control Group: (n = 53, 53 analysed): warfarin started on day 10, initial dose 10 mg, titred so INR 1.5-2.0 for 12 weeks. INR monitored weekly.
    Experimental Group: (n = 53, 53 analysed): subcutaneous heparin every 12 hours (aPTT checked 6 hours later for the first three days) for 12 weeks. No monitoring on discharge from hospital.
    All patients had intravenous heparin for 14 days, titred to a aPTT 1.5-2.0.
    100% followed for 12 weeks
    Outcome notes:
    • recurrent pulmonary embolism : diagnosed by symptoms and positive pulmonary angiogram
    • recurrent deep vein thrombosis : diagnosed by symptoms and positive venogram within 24 hours

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    major bleed 12 weeks 3
    (5.66%)    		 0
    (0.00%)    		 100%
    (% to %)    		 5.66%
    (-0.56% to 11.9%)    		 18
    (NNT = 8 to infinity;
    NNH = 180 to infinity)
    any bleed 12 weeks 9
    (17.0%)    		 1
    (1.89%)    		 89%
    (15% to 99%)    		 15.1%
    (4.34% to 15.9%)    		 7
    (4 to 23)
    death 12 weeks 5
    (9.43%)    		 7
    (13.2%)    		 -40%
    (-313% to 53%)    		 -3.77%
    (-15.8% to 8.27%)    		 -27
    (NNT = 12 to infinity;
    NNH = 6 to infinity)
    recurrent pulmonary embolism 12 weeks 1
    (1.89%)    		 0
    (0.00%)    		 100%
    (% to %)    		 1.89%
    (-1.78% to 5.55%)    		 53
    (NNT = 18 to infinity;
    NNH = 56 to infinity)
    recurrent deep vein thrombosis 12 weeks 4
    (7.55%)    		 5
    (9.43%)    		 -25%
    (-340% to 64%)    		 -1.89%
    (-12.5% to 8.72%)    		 -53
    (NNT = 11 to infinity;
    NNH = 8 to infinity)

    Comments

    1. Small numbers in the trial- may, miss small changes.
    2. Trial fails to address risk of osteoporosis when taking long-term heparin.

    Citation

    1. Hull RD, Delmore T, Carter C, et al: Injected subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis. New England Journal of Medicine 1982; 306 (4): 189-194
    Search Terms: anticoag* in Cochrane
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient proximal DVT
    Intervention or Exposure subcutaneous heparin
    Comparison warfarin
    Outcome recurrent DVT/PE, major bleed