Deep vein thrombosis: LMWH was not clearly as effective as warfarin for long-term anticoagulation.

Clinical bottom line (level 1b-)

  1. In patients with deep vein thrombosis, low molecular weight heparin was not clearly as effective as warfarin for long-term anticoagulation.
Pini et al: Thrombosis and Haemostasis 1994; 72 (2): 191-197
Expires June 2003

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: university hospital, Italy

187 patients (aged mean 65 years, 54% male) acute deep vein thrombosis, diagnosed by venogram or impedance plethysmography and d-dimer assay

Excluded if
  • <18 years old
  • active bleed, or bleeding disorder
  • pregnant
  • clinically suspected pulmonary embolism
  • two or more episodes of DVT/PE
  • history of heparin-induced thrombocytopenia
  • life expectancy <3 months


    • Control Group: (n = 94, 94 analysed): anticoagulated with warfarin for three months. Warfarin started on day 6- aimed for INR 2.0-3.5
    Experimental Group: (n = 93, 93 analysed): anticoagulated with enoxaparin started on day 11, 40 mg twice daily, given subcutaneously by patients, relatives, 'occasionally by visiting nurses' for three months
    All patients had 10 days of heparin 250 units/kg every 12 hours; adjusted so aPTT 1.5-2.5, with 5000 units loading dose. All walked on day 3, wearing compression stockings.
    100% followed for 12 months
    Outcome notes:
    • recurrent DVT/PE : DVT diagnosed by venogram; PE diagnosed by ventilation-perfusion scan, pulmonary angiogram, autopsy
    • major bleed : fall in Hb 2g/dl and intracranial/retroperitoneal bleed

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent DVT/PE 3 months 4
    (4.26%)    		 6
    (6.45%)    		 -52%
    (-420% to 56%)    		 -2.20%
    (-8.64% to 4.25%)    		 -46
    (NNT = 24 to infinity;
    NNH = 12 to infinity)
    recurrent DVT/PE 12 months 8
    (8.51%)    		 16
    (17.2%)    		 -102%
    (-349% to 9%)    		 -8.69%
    (-18.2% to 0.83%)    		 -12
    (NNT = 121 to infinity;
    NNH = 5 to infinity)
    major bleed 12 months 3
    (3.19%)    		 3
    (3.23%)    		 -1%
    (-388% to 79%)    		 -0.03%
    (-5.09% to 5.02%)    		 -2900
    (NNT = 20 to infinity;
    NNH = 20 to infinity)
    death 12 months 8
    (8.51%)    		 11
    (11.8%)    		 -39%
    (-230% to 41%)    		 -3.32%
    (-12.0% to 5.34%)    		 -30
    (NNT = 19 to infinity;
    NNH = 8 to infinity)

  • 30% of patients continued warfarin for nine months, 15% for twelve months- unclear why. This would overestimate the benefit of warfarin- this may occur anyway with unblinded trial.

    • Comments

    1. Study may not be large enough to demonstrate small changes in mortality or bleeding rate.
    2. No data on side-effects were given, eg. thrombocytopenia or osteopenia.

    Citation

    1. Pini M, Aiello S, Manotti C, et al: Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thrombosis and Haemostasis 1994; 72 (2): 191-197
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer:

    Clinical Question.
    Patient acute DVT
    Intervention or Exposure LMWH long-term
    Comparison warfarin long-term
    Outcome recurrent PE/DVT