Deep vein thrombosis: first episode: fewer recurrences occurred on six months of warfarin compared with six weeks.

Clinical bottom line (level 1b)

  1. Patients with a first episode of deep vein thrombosis or pulmonary embolism who took six months of oral anticoagulant therapy, have fewer recurrences of venous thromboembolism compared with those on six weeks of therapy (NNT = 12 at 2 years) .
  2. There was no clear difference in mortality or major haemorrhage between the two groups.
  3. There was no clear benefit in extending anticoagulation beyond six weeks for patients with temporary risk factors.
  4. About 10% of patients on six months of therapy got a further DVT or PE.
Schulman et al: New England Journal of Medicine 1995; 332 (25): 1661-1665
Expires September 2003

The study

Unblinded concealed randomised trial without intention-to-treat
Setting: sixteen centres, Sweden

897 patients (aged mean 61 years, 56% male) first episode of deep venous thrombosis or pulmonary embolism. DVT confirmed by venogram. PE confirmed by angiography or chest radiography and perfusion-ventilation lung scanning

Excluded if
  • <15 years old
  • pregnant
  • allergy to warfarin or dicumarol
  • indication for continuous oral anticoagulation
  • paralysis of the affected leg
  • contraindication to compression stocking use
  • current or previous venous ulcer
  • more than one previous thromboembolic event
  • congenital deficiency of antithrombin, protein C or protein S
  • cancer


    • Control Group: (n = 443, 443 analysed): anticoagulated for six weeks
    Experimental Group: (n = 454, 454 analysed): anticoagulated for six months
    All patients were treated with oral anticoagulation with warfarin sodium or dicoumarol, targeted to an INR of 2.0 to 2.85.
    100% followed for 2 years

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    recurrent PE/DVT 2 years 80
    (18.1%)    		 43
    (9.47%)    		 48%
    (26% to 63%)    		 8.59%
    (4.11% to 13.1%)    		 12
    (8 to 24)
    major haemorrhage 2 years 1
    (0.23%)    		 5
    (1.10%)    		 -388%
    (-4000% to 43%)    		 -0.88%
    (-1.93% to 0.18%)    		 -114
    (NNT = 552 to infinity;
    NNH = 52 to infinity)
    death 2 years 22
    (4.97%)    		 17
    (3.74%)    		 25%
    (-40% to 59%)    		 1.22%
    (-1.45% to 3.89%)    		 82
    (NNT = 26 to infinity;
    NNH = 69 to infinity)
    fatal PE 2 years 2
    (0.45%)    		 3
    (0.66%)    		 -46%
    (-772% to 75%)    		 -0.21%
    (-1.18% to 0.76%)    		 -478
    (NNT = 131 to infinity;
    NNH = 85 to infinity)

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    permanent risk factors for DVT/PE 2 years 65
    (24.2%)    		 35
    (12.2%)    		 50%
    (27% to 65%)    		 12.0%
    (5.60% to 18.3%)    		 8
    (5 to 18)
    temporary risk factors for PE/DVT 2 years 15
    (8.62%)    		 8
    (4.79%)    		 44%
    (-28% to 76%)    		 3.83%
    (-1.45% to 9.11%)    		 26
    (NNT = 11 to infinity;
    NNH = 69 to infinity)

  • For the outcome of permanent risk factors for PE/DVT, there were 269 patients in the control group and 287 in the experimental group. For temporary risk factors, there were 174 patients in the control group and 167 in the experimental group.

    • Comments

    1. No fatal haemorrhages occurred.
    2. 53% of the recurrences in the 6 week group occurred within 6 months of cessation of therapy. From 6 months on, the rate of recurrence in the two groups was similar.
    3. There was no significant benefit for patients with temporary risk factors- however the study was not large enough to exclude this.

    Citation

    1. Schulman S, Rhedin AS, Lindmarker P, et al: A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. New England Journal of Medicine 1995; 332 (25): 1661-1665
    Contributor: Bob Phillips, Chris Ball and Clare Wotton, May 2000
    Reviewer:

    Clinical Question.
    Patient first episode of DVT or PE
    Intervention or Exposure anticoagulated for 6 months
    Comparison anticoagulated for 6 weeks
    Outcome recurrence