Fondaparinux for Isolated Superficial Vein Thrombosis of the Legs: A Cost-Effectiveness Analysis

Abstract

Conclusion: Fondaparinux for 45 days is not cost-effective when treating patients with isolated superficial venous thrombosis (SVT) of the legs. Summary: SVT is a frequent condition, and at the time diagnosis, up to 25% of patients may have associated deep venous thrombosis or pulmonary embolism (Decousus H et al, Ann Inter Med 2010;152:218-24). However, patients recruited for the Decousus study were from vascular medicine specialists and may thus represent a population of more severe cases. Indeed, the clinical impression is that although isolated SVT can on rare occasion be associated with significant VTE events, in most cases, the disease has a very benign course, at least in the short-term. Treatment of isolated SVT is therefore controversial. The recently published Comparison of Arixtra in Lower Limb SVT With Placebo (CALISTO) study randomized 3000 patients with isolated lower extremity SVT to prophylactic fondaparinux (2.5 mg daily for 45 days) vs placebo (Decousus H et al, N Engl J Med 2010;363:1222-32). With respect to the composite outcomes of death, deep venous thrombosis, and extension or recurrence of SVT, fondaparinux was superior to placebo. There was, however, a high number needed to treat to avoid one complication such as pulmonary embolism (n = 300). Fondaparinux is expensive, and therefore, the authors of this study sought to evaluate its cost-effectiveness by creating decision-tree modeling with data derived primarily from the CALISTO study and published literature. The decision-tree model compared fondaparinux (2.5 mg daily for 45 days) vs no treatment of SVT. The model included all clinical events associated with SVT, its treatment, complications, and all respective quality-adjustment factors. Measured outcomes included VTE clinical events (major hemorrhage, death) quality-adjusted life-years, (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). A lifetime time horizon analysis was used from a health care system perspective. One-way probabilistic sensitivity analysis was used to evaluate parameter uncertainty. In 10,000 patients, they estimated that fondaparinux would prevent 123 VTE events and two deaths. On a per-patient basis, incremental QALY compared with no treatment was 0.04/day at an incremental cost of $1,734. This results in an ICER of $500,000 per QALY. ICER remained >$100,000 per QALY with a one-way sensitivity analysis. Based on probabilistic sensitivity analysis, the probability that fondaparinux was cost-effective was 1% at a willingness-to-pay $100,000 per QALY. Comment: The data indicate that fondaparinux as a blanket treatment for SVT of the lower extremities is not anywhere near cost-effective based on the commonly accepted threshold of ∼$50,000 per QALY to guide recommendations in most clinical situations. The authors did not address whether improved cost-effectiveness could be achieved by targeting specific subgroups with SVT with a likely higher incidence of VTE. Such groups may include men, those with severe chronic venous insufficiency, SVT without varicose veins, and patients with a history of cancer, previous VTE, or a known thrombophilia. Future studies of SVT potentially could yield more robust recommendations for treatment if higher-risk subgroups were targeted in those studies.