Tinzaparine ou HEparine Standard: Evaluations dans l’Embolie pulmonaire


Initial treatment of acute symptomatic PE

Close this section


To compare the efficacy and safety of fixed-dose tinzaparin compared with adjusted-dose UFH in patients with acute symptomatic PE

Close this section

Trial design

Randomized, open study with parallel groups
Active treatment: tinzaparin 175 anti-factor Xa/kg s.c. once daily for at least 5 days and until the concomitant oral anticoagulant therapy resulted in an INR ≥2 (n=304)
Control treatment: UFH 50 IU/kg i.v. bolus followed by 500 IU/kg/day continuous i.v. infusion (target aPTT 2–3 times the control value) for at least 5 days and until the oral anticoagulant therapy induced an INR ≥2.0 (n=308)

Close this section


Primary endpoint: composite of recurrent thromboembolism, major bleeding, and death within the first 8 days and at day 90
Secondary endpoint: change from day 1 to day 8 in the extent of scintigraphically detectable pulmonary vascular obstruction

Close this section

Trial participants

612 consecutive patients (mean age 67 years) with documented acute symptomatic PE who did not require thrombolytic therapy or embolectomy

Close this section


Efficacy outcome: At 8 days, the incidence of the primary endpoint (death, symptomatic recurrent thromboembolism or major bleeding) was similar in the tinzaparin and UFH group (3.0% vs. 2.9%). By day 90, this incidence was slightly, but not significantly, lower in patients assigned to tinzaparin than in patients assigned to UFH (5.9% vs. 7.1%). From day 1 to day 8, 4 of 304 patients (1.3%) receiving tinzaparin died, as compared with 3 of 308 patients (1.0%) receiving UFH. The mortality rates at 3 months were 3.9% and 4.5%, respectively. At day 8, the absolute decrease in pulmonary vascular obstruction was 18.4±13.5% in 258 patients assigned to tinzaparin and 19.0±13.9% in 260 patients assigned to UFH
Safety outcome: At day 8, 1.0% in the tinzaparin group and 1.6% in the UFH group had episodes of major bleeding. By 3 months the incidences were 2.0% and 2.6%, respectively. During the initial treatment, minor bleeding was noted in 17 patients receiving tinzaparin and 8 patients receiving UFH (p=0.10)

Close this section


Efficacy: Treatment of confirmed PE with fixed-dose tinzaparin was as effective as treatment with adjusted-dose UFH
Safety: The incidence of major bleeding was similar with tinzaparin and UFH throughout the study

Close this section


Simonneau G, Sors H, Charbonnier B, Page Y, Laaban J-P, Azarian R, Laurent M, Hirsch J-L, Ferrari E, Bosson J-L, Mottier D, Beau B, for the THÉSÉE Study Group. A comparison of low-molecular weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997;337:663-669

Close this section

Corresponding author

Gérald Simonneau, MD, Service de Pneumologie et Réanimation, Hôpital Antoine Béclère, 157 rue de la Porte de Trivaux, 92141 Clamart, France

Close this section

Back To List

Recommend pageBack to top