Fondaparinux Reduces All Types of Symptomatic Thromboembolic Complications in Patients with Superficial-Vein Thrombosis in the Legs: Data From the CALISTO Study

The CALISTO trial demonstrated the clinical benefit of anticoagulant therapy in patients with spontaneous isolated superficial-vein thrombosis (SVT) in the legs (n=3002).¹ Compared with placebo, a 45-day once-daily subcutaneous treatment with fondaparinux 2.5 mg was associated with a 85% relative reduction in the risk of the composite of all-cause death and adjudicated symptomatic thromboembolic complications at day 47, a benefit that was maintained at 30-day follow-up (day 77) and was not associated with an increased bleeding risk. The benefit of fondaparinux was observed with the same magnitude on each thromboembolic component of the primary efficacy outcome, including symptomatic extension of SVT to the sapheno-femoral junction (SFJ). However, although all symptomatic extensions of the index SVT were reported and reviewed, only those within 3 cm of the SFJ were counted for the primary outcome. To better characterize the efficacy of fondaparinux we used a new composite efficacy outcome, including all symptomatic extensions of SVT, regardless of their distance from the SFJ.

The composite thromboembolic outcome of the original primary endpoint of the CALISTO trial included symptomatic pulmonary embolism (PE), symptomatic deep-vein thrombosis (DVT), symptomatic extension of the index SVT to ≤3 cm (EXT ≤3 cm) from the SFJ, and symptomatic recurrence of SVT (composite outcome CO-1). In a post-hoc analysis, we additionally included in the composite outcome (CO-2) all symptomatic extensions of the index SVT regardless of their final distance from the SFJ (EXT >3 cm). All symptomatic thromboembolic events were confirmed by appropriate objective tests and reviewed by an independent, central, blinded adjudication committee.

Overall, symptomatic EXT ≤3 cm and EXT >3 cm of index SVT at day 77 were reported in 59 (2.0%) and 68 patients (2.3%), respectively. Compared with placebo, fondaparinux significantly reduced at day 77 both the rate of CO-1, from 6.2% (93/1500) to 1.1% (17/1502; RR, 0.18, 95% confidence interval [CI], 0.11 to 0.31, p<0.001) and the rate of CO-2, from 9.4% (141/1500) to 1.9% (29/1502; RR, 0.21, 95% CI, 0.14 to 0.30, p<0.001). ¹ Fondaparinux significantly lowered the rate of symptomatic EXT >3 cm from 3.7% (56/1500) to 0.8% (12/1501; RR, 0.21, 95% CI, 0.12 to 0.40, p<0.001), a reduction similar in magnitude to the reduction of EXT ≤3 cm. In the placebo group, 5/54 (9.3%) patients with a symptomatic EXT ≤3 cm and 5/56 (8.9%) of those with a symptomatic EXT >3 cm also experienced symptomatic PE or DVT during the course of the trial. In the fondaparinux group, none of the patients with SVT extension, reaching ≤3 cm or >3 cm from the SFJ, experienced symptomatic PE or DVT. Fondaparinux was associated with less use of medical resources, particularly in terms of surgery to treat SVT or need for anticoagulant therapy (Table).

Extension of the index SVT is a clinically relevant complication of the disease, regardless of the distance of the extension from the SFJ, and is associated with additional use of medical resources. Compared with placebo, fondaparinux reduced the rate of symptomatic thromboembolic complications in patients with spontaneous isolated SVT in the legs.

¹Decousus H, et al; CALISTO Study Group. N Engl J Med 2010;363:1222-32.

Leizorovicz:BMS: Research Funding; Sanofi Aventis: Honoraria; Bayer: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria. Off Label Use: Fondaparinux for the treatment of Superficial Vein Thrombosis, labelled in Europe. Prandoni:GSK: Membership on an entity's Board of Directors or advisory committees. Décousus:GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees.