COMPARING SUBCUTANEOUS DANAPAROID WITH INTRAVENOUS UNFRACTIONATED HEPARIN FOR THE TREATMENT OF VENOUS THROMBOEMBOLISM - A RANDOMIZED CONTROLLED TRIAL

Objective: To compare the efficacy and safety of two subcutaneous dose s of danaparoid with that of continuous intravenous administration of unfractionated heparin in the treatment of venous thromboembolism. Des ign: An open-label, randomized, multicenter clinical trial. Setting: O ne university hospital and two university-affiliated hospitals. Patien ts: 209 patients suspected to have venous thromboembolism. Of these, 1 88 had a confirmed diagnosis (by ventilation-perfusion lung scan and u ltrasonography or contrast venography of the leg) and received study m edication. Interventions: Patients were randomly assigned to either lo w-dose danaparoid (intravenous loading dose of 1250 U followed by 1250 U administered subcutaneously twice dairy [n = 65]); high-dose danapa roid (intravenous loading dose of 2000 U followed by 2000 U administer ed subcutaneously twice daily [n = 63]); or unfractionated heparin (in travenous loading dose of 2500 U followed by dose-adjusted continuous infusion [n = 60]). Treatment lasted at least 5 days and was continued until anticoagulation (achieved with acenocoumarol) was adequate. Mea surements: Efficacy determined clinically and by repeated imaging test s on treatment days 5 to 8; safety determined by daily assessment for bleeding. Results: Two lung scans were done in each of 179 patients; u ltrasonography or venography of the leg was done twice in each of 173 patients; and both repeated leg and lung tests were done in 166 patien ts. A significant reduction in recurrence or extension of venous throm boembolism was seen in patients receiving high-dose danaparoid (8 of 6 3 [13%]) compared with patients receiving intravenous unfractionated h eparin (17 of 60 [28%]; relative risk, 0.45 [95% CI, 0.21 to 0.96]). F our of 61 patients receiving high-dose danaparoid (7%) and 14 of 58 pa tients receiving unfractionated heparin (24%) had recurrence of pulmon ary embolism (relative risk, 0.27 [CI, 0.09 to 0.78]); 3 of 58 patient s receiving high-dose danaparoid (5%) and 6 of 54 patients receiving u nfractionated heparin (11%) had recurrence of deep venous thrombosis ( relative risk, 0.47 [CI, 0.12 to 1.77]). Occurrence of major and minor bleeding was similar in the three groups; major bleeding occurred in 1 patient receiving low-dose danaparoid, 1 patient receiving high-dose danaparoid, and 2 patients receiving heparin. Conclusions: Our result s suggest that high-dose danaparoid is safer and more effective than u nfractionated heparin for the treatment of venous thromboembolism.