Fondaparinux Reduces Events From Superficial Vein Thromboses

SAN DIEGO – In patients with spontaneous, isolated superficial vein thrombosis, a 45-day course of fondaparinux significantly reduced the rate of systemic thromboembolic complications compared with placebo, including events linked to thrombi with extensions more than 3 cm from the saphenofemoral junction, according to results of a post hoc analysis from the CALISTO trial.

Among patients with extension of a superficial vein thrombosis (SVT) either to 3 cm or less or more than 3 cm from the saphenofemoral junction, fondaparinux reduced the rate of symptomatic venous thromboembolic events (VTEs) by 79%, Dr. Alain Leizorovicz of the University of Lyon (France) reported at the annual meeting of the American Society of Hematology.

The results of the post hoc analysis were similar to those seen in the original analysis of the CALISTO (Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis With Placebo) trial. The results of the original analysis were first presented at the 2009 annual meeting of the American Society of Hematology, and published in the New England Journal of Medicine (N. Engl. J. Med. 2010;363:1222-32).

At that time, investigators showed that 2.5 mg fondaparinux injected subcutaneously once daily for 45 days reduced by 82% the rate of the primary end point, a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of SVT at day 47.

Principal investigator Dr. Hervé Décousus explained in an interview that the trial was designed with a pragmatic end point, looking at the effect of fondaparinux, a factor Xa inhibitor, on the incidence of symptomatic SVT with heads that extended no more than 3 cm from the saphenofemoral junction.

"These are considered by the vast majority of clinicians to be a proximal DVT [deep vein thrombosis]. Everybody accepted the idea that extension to the saphenofemoral junction was a very clinically pertinent end point," said Dr. Décousus from the Hôpital Nord in Saint-Étienne, France.

The CALISTO trial was a randomized, double-blind study comparing fondaparinux to placebo in 3,002 adults with symptomatic lower-limb SVT at least 5 cm long on compression ultrasonography. A total of 1,502 patients were assigned to receive fondaparinux and 1,500, to placebo. Patients were followed for 77 days from the initiation of therapy.

Because symptomatic extensions of index SVT to more than 3 cm from the saphenofemoral junction were not included in the primary end point, the authors created a secondary, post hoc end point considering more distal SVT.

At day 77, symptomatic SVTs within 3 cm of the SVT were seen in 59 (2% of all patients) and extensions to greater than 3 cm were seen in 68 (2.3%). The rate of the secondary thromboembolic outcome used in the post hoc analysis (a composite of symptomatic pulmonary emboli, DVT, extension of the index SVT, and symptomatic recurrence of the index SVT) among patients on placebo was 9.4%, compared with 1.9% for patients on fondaparinux (relative risk, 0.21; P less than .001).

Among patients on placebo, 9.3% of those with a symptomatic SVT within 3 cm and 8.9% of those with an extension beyond 3 cm had a symptomatic pulmonary embolic or DVT event during the trial. In contrast, no patients on fondaparinux experienced either event.

Patients on fondaparinux also used fewer analgesics, antiplatelet agents, and anticoagulants and had fewer ultrasound exams, surgeries to treat SVT, and hospitalizations after a thromboembolic event, compared with patients on placebo, the authors noted.

CALISTO was funded by GlaxoSmithKline. Dr. Leizorovicz disclosed receiving research funding, honoraria, and/or consulting fees from GSK, Bristol-Myers Squibb, Sanofi-Aventis, Bayer, and Boehringer Ingelheim. He also disclosed off-label use of fondaparinux for the treatment of SVT. Dr. Décousus disclosed serving on the board of directors or advisory committees for, and/or receiving research funding from, GSK, Bristol-Meyers Squibb, Boehringer Ingleheim, and Daiichi Sankyo. Coauthor Dr. Paolo Prandoni disclosed membership on a board or advisory committee for GSK.

SAN DIEGO – In patients with spontaneous, isolated superficial vein thrombosis, a 45-day course of fondaparinux significantly reduced the rate of systemic thromboembolic complications compared with placebo, including events linked to thrombi with extensions more than 3 cm from the saphenofemoral junction, according to results of a post hoc analysis from the CALISTO trial.

Among patients with extension of a superficial vein thrombosis (SVT) either to 3 cm or less or more than 3 cm from the saphenofemoral junction, fondaparinux reduced the rate of symptomatic venous thromboembolic events (VTEs) by 79%, Dr. Alain Leizorovicz of the University of Lyon (France) reported at the annual meeting of the American Society of Hematology.

The results of the post hoc analysis were similar to those seen in the original analysis of the CALISTO (Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis With Placebo) trial. The results of the original analysis were first presented at the 2009 annual meeting of the American Society of Hematology, and published in the New England Journal of Medicine (N. Engl. J. Med. 2010;363:1222-32).

At that time, investigators showed that 2.5 mg fondaparinux injected subcutaneously once daily for 45 days reduced by 82% the rate of the primary end point, a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of SVT at day 47.

Principal investigator Dr. Hervé Décousus explained in an interview that the trial was designed with a pragmatic end point, looking at the effect of fondaparinux, a factor Xa inhibitor, on the incidence of symptomatic SVT with heads that extended no more than 3 cm from the saphenofemoral junction.

"These are considered by the vast majority of clinicians to be a proximal DVT [deep vein thrombosis]. Everybody accepted the idea that extension to the saphenofemoral junction was a very clinically pertinent end point," said Dr. Décousus from the Hôpital Nord in Saint-Étienne, France.

The CALISTO trial was a randomized, double-blind study comparing fondaparinux to placebo in 3,002 adults with symptomatic lower-limb SVT at least 5 cm long on compression ultrasonography. A total of 1,502 patients were assigned to receive fondaparinux and 1,500, to placebo. Patients were followed for 77 days from the initiation of therapy.

Because symptomatic extensions of index SVT to more than 3 cm from the saphenofemoral junction were not included in the primary end point, the authors created a secondary, post hoc end point considering more distal SVT.

At day 77, symptomatic SVTs within 3 cm of the SVT were seen in 59 (2% of all patients) and extensions to greater than 3 cm were seen in 68 (2.3%). The rate of the secondary thromboembolic outcome used in the post hoc analysis (a composite of symptomatic pulmonary emboli, DVT, extension of the index SVT, and symptomatic recurrence of the index SVT) among patients on placebo was 9.4%, compared with 1.9% for patients on fondaparinux (relative risk, 0.21; P less than .001).

Among patients on placebo, 9.3% of those with a symptomatic SVT within 3 cm and 8.9% of those with an extension beyond 3 cm had a symptomatic pulmonary embolic or DVT event during the trial. In contrast, no patients on fondaparinux experienced either event.

Patients on fondaparinux also used fewer analgesics, antiplatelet agents, and anticoagulants and had fewer ultrasound exams, surgeries to treat SVT, and hospitalizations after a thromboembolic event, compared with patients on placebo, the authors noted.

CALISTO was funded by GlaxoSmithKline. Dr. Leizorovicz disclosed receiving research funding, honoraria, and/or consulting fees from GSK, Bristol-Myers Squibb, Sanofi-Aventis, Bayer, and Boehringer Ingelheim. He also disclosed off-label use of fondaparinux for the treatment of SVT. Dr. Décousus disclosed serving on the board of directors or advisory committees for, and/or receiving research funding from, GSK, Bristol-Meyers Squibb, Boehringer Ingleheim, and Daiichi Sankyo. Coauthor Dr. Paolo Prandoni disclosed membership on a board or advisory committee for GSK.

SAN DIEGO – In patients with spontaneous, isolated superficial vein thrombosis, a 45-day course of fondaparinux significantly reduced the rate of systemic thromboembolic complications compared with placebo, including events linked to thrombi with extensions more than 3 cm from the saphenofemoral junction, according to results of a post hoc analysis from the CALISTO trial.

Among patients with extension of a superficial vein thrombosis (SVT) either to 3 cm or less or more than 3 cm from the saphenofemoral junction, fondaparinux reduced the rate of symptomatic venous thromboembolic events (VTEs) by 79%, Dr. Alain Leizorovicz of the University of Lyon (France) reported at the annual meeting of the American Society of Hematology.

The results of the post hoc analysis were similar to those seen in the original analysis of the CALISTO (Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis With Placebo) trial. The results of the original analysis were first presented at the 2009 annual meeting of the American Society of Hematology, and published in the New England Journal of Medicine (N. Engl. J. Med. 2010;363:1222-32).

At that time, investigators showed that 2.5 mg fondaparinux injected subcutaneously once daily for 45 days reduced by 82% the rate of the primary end point, a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of SVT at day 47.

Principal investigator Dr. Hervé Décousus explained in an interview that the trial was designed with a pragmatic end point, looking at the effect of fondaparinux, a factor Xa inhibitor, on the incidence of symptomatic SVT with heads that extended no more than 3 cm from the saphenofemoral junction.

"These are considered by the vast majority of clinicians to be a proximal DVT [deep vein thrombosis]. Everybody accepted the idea that extension to the saphenofemoral junction was a very clinically pertinent end point," said Dr. Décousus from the Hôpital Nord in Saint-Étienne, France.

The CALISTO trial was a randomized, double-blind study comparing fondaparinux to placebo in 3,002 adults with symptomatic lower-limb SVT at least 5 cm long on compression ultrasonography. A total of 1,502 patients were assigned to receive fondaparinux and 1,500, to placebo. Patients were followed for 77 days from the initiation of therapy.

Because symptomatic extensions of index SVT to more than 3 cm from the saphenofemoral junction were not included in the primary end point, the authors created a secondary, post hoc end point considering more distal SVT.

At day 77, symptomatic SVTs within 3 cm of the SVT were seen in 59 (2% of all patients) and extensions to greater than 3 cm were seen in 68 (2.3%). The rate of the secondary thromboembolic outcome used in the post hoc analysis (a composite of symptomatic pulmonary emboli, DVT, extension of the index SVT, and symptomatic recurrence of the index SVT) among patients on placebo was 9.4%, compared with 1.9% for patients on fondaparinux (relative risk, 0.21; P less than .001).

Among patients on placebo, 9.3% of those with a symptomatic SVT within 3 cm and 8.9% of those with an extension beyond 3 cm had a symptomatic pulmonary embolic or DVT event during the trial. In contrast, no patients on fondaparinux experienced either event.

Patients on fondaparinux also used fewer analgesics, antiplatelet agents, and anticoagulants and had fewer ultrasound exams, surgeries to treat SVT, and hospitalizations after a thromboembolic event, compared with patients on placebo, the authors noted.

CALISTO was funded by GlaxoSmithKline. Dr. Leizorovicz disclosed receiving research funding, honoraria, and/or consulting fees from GSK, Bristol-Myers Squibb, Sanofi-Aventis, Bayer, and Boehringer Ingelheim. He also disclosed off-label use of fondaparinux for the treatment of SVT. Dr. Décousus disclosed serving on the board of directors or advisory committees for, and/or receiving research funding from, GSK, Bristol-Meyers Squibb, Boehringer Ingleheim, and Daiichi Sankyo. Coauthor Dr. Paolo Prandoni disclosed membership on a board or advisory committee for GSK.