title: 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.
abstract: 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.
authors.affiliation: Medical Clinic, Charité University Clinic, Campus Virchow Clinic, Berlin, Germany. hanno.riess@charite.de
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.forename: Klaus
authors.initials: K
authors.lastname: Koppenhagen
authors.forename: Alexander
authors.initials: A
authors.lastname: Tolle
authors.forename: Bettina
authors.initials: B
authors.lastname: Kemkes-Matthes
authors.forename: Michael
authors.initials: M
authors.lastname: Gräve
authors.forename: Frantisek
authors.initials: F
authors.lastname: Patek
authors.forename: Michael
authors.initials: M
authors.lastname: Drexler
authors.forename: Hans-Joachim G
authors.initials: HJ
authors.lastname: Siemens
authors.forename: Job
authors.initials: J
authors.lastname: Harenberg
authors.forename: Gottfried
authors.initials: G
authors.lastname: Weidinger
authors.forename: Joachim
authors.initials: J
authors.lastname: Brom
authors.forename: Sylvia
authors.initials: S
authors.lastname: Haas
mesh_terms: D000368:Aged; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013921:Thrombocytopenia / Q000139:chemically induced; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; C403769:certoparin