Testing for Factor V Leiden in Patients with Pulmonary or Venous Thromboembolism: A Cost-Effectiveness Analysis

Background . Survivors of venous thromboembolism who have the factor V Leiden mutation have an increased risk of recurrent venous thromboembolism (VTE), but the cost-effectiveness of testing for factor V Leiden has not been assessed. Methods . We used a Markov state transition decision model to evaluate the cost-effectiveness of factor V Leiden testing and treatment strategies in survivors of VTE using a societal perspective for costs, effectiveness—measured in quality-adjusted life years, and incremental cost-effectiveness. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles. Cost estimates were derived from Medicare reimbursement and other sources. The analysis examined 3 hypothetical cohorts of 35-year-old women having suffered their 1st episode of VTE. Interventions included oral anticoagulant therapy for 6 months versus testing. Patients found to have the factor V Leiden mutation were then treated with either 3 years or lifelong oral anticoagulant therapy. Results . Total costs for testing followed by 3 years of treatment were $9,676, whereas those for no testing were $10,392 and those for testing followed by lifelong therapy were $13,179. Testing followed by 3 years of treatment increased quality-adjusted life expectancy by roughly 0.15 years. In sensitivity analyses using a more plausible constant risk model of recurrent VTE, testing followed by lifelong anticoagulation was the favored strategy. However, the marginal cost-effectiveness ratio was highly dependent on the rate of recurrent VTE, the risk of major hemorrhage, prevalence of factor V Leiden, patient age, and the efficacy of anticoagulation therapy. Conclusions . Testing followed by lifelong anticoagulation is unlikely to be a cost-effective strategy in patient populations with a very low prevalence of factor V Leiden; for those with a lower risk for recurrent VTE, such as patients with a clear precipitant; or for patients with risk factors for bleeding while receiving anticoagulant therapy. The only patients for whom testing followed by lifelong anticoagulant therapy may be a reasonable strategy are those with no obvious precipitant for VTE (i.e., idiopathic VTE) who are at low risk for bleeding complications from oral anticoagulant therapy. These results highlight the need for further clinical investigation and the development of multivariable models predicting the risk of recurrent VTE based on factor V Leiden status, idiopathic versus precipitated VTE, treatment, and the coinheritance of other common thrombophilias, such as the prothrombin gene mutation.