A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire

N Engl J Med. 1997 Sep 4;337(10):663-9. doi: 10.1056/NEJM199709043371002.


Background: Low-molecular-weight heparin appears to be at least as effective and safe as standard, unfractionated heparin for the treatment of deep-vein thrombosis, but only limited data are available on the use of low-molecular-weight heparin to treat acute symptomatic pulmonary embolism.

Methods: We randomly assigned 612 patients with symptomatic pulmonary embolism who did not require thrombolytic therapy or embolectomy to either subcutaneous low-molecular-weight heparin (tinzaparin) given once daily in a fixed dose or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy was begun between the first and the third day and was given for at least three months. We compared the treatments at day 8 and day 90 with respect to a combined end point of recurrent thromboembolism, major bleeding, and death.

Results: In the first eight days of treatment, 9 of 308 patients assigned to receive unfractionated heparin (2.9 percent) reached at least one of the end points, as compared,with 9 of 304 patients assigned to low-molecular-weight heparin (3.0 percent; absolute difference, 0.1 percentage point; 95 percent confidence interval, -2.7 to 2.6). By day 90, 22 patients assigned to unfractionated heparin (7.1 percent) and 18 patients assigned to low-molecular-weight heparin (5.9 percent) had reached at least one end point (P=0.54; absolute difference, 1.2 percentage points; 95 percent confidence interval, -2.7 to 5.1). The risk of major bleeding was similar in the two treatment groups throughout the study.

Conclusions: Under the conditions of this study, initial subcutaneous therapy with the low-molecular-weight heparin tinzaparin appeared to be as effective and safe as intravenous unfractionated heparin in patients with acute pulmonary embolism.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Cause of Death
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Embolism / diagnostic imaging
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality
  • Radionuclide Imaging
  • Recurrence
  • Thromboembolism / drug therapy
  • Thromboembolism / epidemiology
  • Tinzaparin
  • Treatment Outcome


  • Anticoagulants
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Tinzaparin
  • Heparin