Breast cancer: low-dose warfarin reduced venous thromboembolism during chemotherapy

Clinical bottom line (level 1b)

  1. 4% of women with metastatic breast carcinoma receiving chemotherapy develop a PE or DVT
  2. Very-low-dose warfarin reduces DVT and PE in women with metastatic breast carcinoma receiving chemotherapy (NN T = 27 at 3 years) .
  3. Warfarin has no clear effect on haemorrhage or mortality.
Levine et al: Lancet 1994; 343 : 886-889
Expires November 2003

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: 11 cancer treatment centers, Canada, USA, Italy.

315 patients (aged mean 57, 100% female) with metastatic breast carcinoma who had begun first- or second-line chemotherapy ~ 4 weeks before study entry

Excluded if
  • Eastern Cooperative Oncology Group performance status of 3 or more
  • underlying bleeding disorder or peptic ulcer disease
  • direct bilirubin levels > twice normal
  • prothrombin time international normalized ratio (INR) of 1.3 or more
  • platelet count < 50 x 10 9 /L
  • history of alcohol abuse
  • overt brain metastases, presence of psychiatric or affective disorder
  • need for long-term oral anticoagulant therapy
  • expected survival < 3 months
  • concurrent hormonal treatment
  • inability to attend follow-up visits for geographical reasons

    Control Group: (n = , analysed): placebo
    Experimental Group: (n = , analysed): low-dose warfarin 1 mg daily for 6 weeks. Then dose adjusted to INR 1.3 -1.9. Treatment with warfarin or placebo continued for 1 week after termination of chemotherapy. (mean dose of warfarin 2.6 mg).
    Received low-dose warfarin or placebo during chemotherapy
    84% followed for 3 years

    The evidence

    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NN T
    (95% CI)
    DVT or PE 3 years 7
    (4.40%)    		 1
    (0.66%)    		 85%
    (-20% to 98%)    		 3.74%
    (0.31% to 7.18%)    		 27
    (14 to 330)
    haemorrhage 3 years 2
    (1.26%)    		 1
    (0.66%)    		 48%
    (-470% to 95%)    		 0.60%
    (-1.56% to 2.76%)    		 170
    (NNT = 36 to infinity;
    NNH = 64 to infinity)
    death 3 years 59
    (37.1%)    		 65
    (42.8%)    		 -15%
    (-51% to 12%)    		 -5.66%
    (-16.5% to 5.22%)    		 -18
    (NNT = 19 to infinity;
    NNH = 6 to infinity)

    Comments

    1. Only 1 event occurred in the treated group (at 202 days) compared with 3 events in the placebo group during the first 35 days.
    2. The benefits are small especially in view of the high mortality rate.

    Citation

    1. Levine M, et al: Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994; 343 : 886-889
    Search Terms: thromboembol* in ACP Journal Club
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient metastatic breast cancer
    Intervention or Exposure low-dose warfarin
    Comparison placebo
    Outcome venous thromboembolism
    		•