Fixed-dose, body weight-independent subcutaneous low molecular weight heparin Certoparin compared with adjusted-dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis

Hanno Riess; Klaus Koppenhagen; Alexander Tolle; Bettina Kemkes-Matthes; Michael Gräve; Frantisek Patek; Michael Drexler; Hans-Joachim G. Siemens; Job Harenberg; Gottfried Weidinger; Joachim Brom; Sylvia Haas

doi:10.1160/TH02-09-0061

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(02): 252-259
DOI: 10.1160/TH02-09-0061

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Fixed-dose, body weight-independent subcutaneous low molecular weight heparin Certoparin compared with adjusted-dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis

for the TH-4Study Group

Hanno Riess

¹Medical Clinic, Charité University Clinic, Campus Virchow Clinic, Berlin, Germany

,

Klaus Koppenhagen

²University Clinic Benjamin Franklin, Berlin, Germany

,

Alexander Tolle

³Novartis Pharma GmbH, Nuremberg, Germany

,

Bettina Kemkes-Matthes

⁴Medical Clinic, Justus Liebig University, Giessen, Germany

,

Michael Gräve

³Novartis Pharma GmbH, Nuremberg, Germany

,

Frantisek Patek

⁵Masarykova Nemocnice, Ústí nad Labem, The Czech Republic

,

Michael Drexler

⁶St Josef’s Hospital, Wiesbaden, Germany

,

Hans-Joachim G. Siemens

⁷Medical Clinic, University of Lubeck, Germany

,

Job Harenberg

⁸Medical Clinic, University Clinic, Mannheim, Germany

,

Gottfried Weidinger

³Novartis Pharma GmbH, Nuremberg, Germany

,

Joachim Brom

³Novartis Pharma GmbH, Nuremberg, Germany

,

Sylvia Haas

⁹Department of Experimental Oncology and Therapeutic Research, Technical University Munich, Germany

› Author Affiliations

Abstract

Summary

Subcutaneous body weight-adjusted low molecular weight heparin (LMWH) has been proven as effective and safe as intravenous aPTT-adjusted unfractionated heparin (UFH) for the treatment of patients with acute deep venous thrombosis (DVT). In this study we evaluate the efficacy of the initial treatment of proximal DVT with a fixed-dose, body weight-independent application of the LMWH Certoparin with a six month follow-up.

In a prospective, multicentre, randomized, active-controlled study 1220 patients with objectively diagnosed proximal DVT were randomly assigned to subcutaneous 8000 U anti-factor Xa of Certoparin twice daily for 10 to 14 days or intravenous aPTT-adjusted UFH for 5 to 8 days. Both regimen were followed by oral anticoagulation for 6 months. The primary end point was the rate of symptomatic and objectively confirmed thromboembolic events within 6 months. The aim of the study was to demonstrate the non-inferiority of the Certoparin regimen as compared to UFH.

The per-protocol analysis revealed 22 (3.8%) thromboembolic events in the Certoparin group and 24 (4.3%) in patients assigned to UFH within 6 months, thereby proving the non-inferiority (p<0.01), confirmed by intent-to-treat analysis (p<0.001). Major bleeding occurred in 6 and 7 patients started on Certoparin or UFH during the treatment period. Thromboembolic events were equally distributed in body weight categories with < 50,50-80 and >80 kg as followed:0,3.6% and 4.1% of patients for the Certoparin group and 0, 4.6% and 4.2% of patients for the UFH group. The same was true for major bleeding complications with 0, 2.9% and 1.5% for Certoparin and 0, 3.5% and 4.2% for UFH. Overall mortality was 1.9 % in the Certoparin group and 2.7 % in the UFH group.

Fixed-dose body weight-independent subcutaneous LMWH Certoparin is at least as efficacious and safe as intravenous aPTT-adjusted UFH for the initial treatment of acute proximal DVT. This effect is maintained during a 6-months follow-up of treatment with oral anticoagulation.

Keywords

Deep venous thrombosis - therapy - low molecular weight heparin

Full Text

References

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