Venous thromboembolism: factor V Leiden and the oral contraceptives increased the risk

Clinical bottom line (level 3b)

  1. The risk of venous thromboembolism in healthy women aged 15-49 was very small (0.02%).
  2. Oral contraceptives independently increased the risk (NNF = 940 for 5 years)
  3. Factor V Leiden independently increased the risk (NNF = 570 for 5 years)
Vanderbroucke et al: Lancet 1994; 344: 1453-1457
Expires September 2003

The study

Case-control study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: anticoagulation clinic, Holland; 1988-93

155 patients (aged mean 35y (range 15y to 49y), first episode of venous thromboembolism

Excluded if
  • malignant disease
  • pregnant or peripeurperal
  • recent miscarriage


    • Cases: 155 patients (% , mean age ): cases of first VTE
    Controls: 155 patients (% , mean age ): friends, relatives or acquaintances matched for age


    Multivariate logistic regression analysis adjusting for obesity, surgery, diabetes and smoking.

    Outcomes studied:
  • first venous thromboembolism

    • The evidence

    Patient expected event rate for first venous thromboembolism: 0.021%
    risk factor first venous thromboembolism
    present    		 first venous thromboembolism
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    OCP use 109 65 6.0
    (3.4 to 10.6)     		952
    (496 to 1980)
    no OCP use 46 104

    risk factor first venous thromboembolism
    present    		 first venous thromboembolism
    absent    		 unadjusted OR
    (95% CI)    		 NNH
    (95% CI)
    Factor V Leiden mutation 35 6 9.3
    (3.6 to 24.1)     		574
    (206 to 1830)
    no Factor V Leiden mutation 120 163

    • Very little multiplicative interaction (synergy) of the two factors (RR=1.2, 95% CI 0.2 to 9.7)

    Comments

    1. Risk of DVT an order of magnitude greater than in survey of women by GPs in UK. This may reflection that the women were already referred to anticoagulation clinic - so controls are not typical of general population

    Citation

    1. Vanderbroucke JP, Koster Ted, Briet E, et al: Increased risk of venous thromboembolism in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-1457
    Contributor: Chris Ball and Bob Phillips, June 1997
    Reviewer:

    Clinical Question.
    Patient women
    Intervention or Exposure oral contraceptive pill
    Comparison both OCP and factor V
    Outcome venous thromboembolism