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 doses of danaparoid with that of continuous intravenous administration of unfractionated heparin in the treatment of venous thromboembolism.

DESIGN

An open-label, randomized, multicenter clinical trial.

SETTING

One university hospital and two university-affiliated hospitals.

PATIENTS

209 patients suspected to have venous thromboembolism. Of these, 188 had a confirmed diagnosis (by ventilation-perfusion lung scan and ultrasonography or contrast venography of the leg) and received study medication.

INTERVENTIONS

Patients were randomly assigned to either low-dose danaparoid (intravenous loading dose of 1250 U followed by 1250 U administered subcutaneously twice daily [n = 65]); high-dose danaparoid (intravenous loading dose of 2000 U followed by 2000 U administered subcutaneously twice daily [n = 63]); or unfractionated heparin (intravenous 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.

MEASUREMENTS

Efficacy determined clinically and by repeated imaging tests on treatment days 5 to 8; safety determined by daily assessment for bleeding.

RESULTS

Two lung scans were done in each of 179 patients; ultrasonography or venography of the leg was done twice in each of 173 patients; and both repeated leg and lung tests were done in 166 patients. A significant reduction in recurrence or extension of venous thromboembolism was seen in patients receiving high-dose danaparoid (8 of 63 [13%]) compared with patients receiving intravenous unfractionated heparin (17 of 60 [28%]; relative risk, 0.45 [95% CI, 0.21 to 0.96]). Four of 61 patients receiving high-dose danaparoid (7%) and 14 of 58 patients receiving unfractionated heparin (24%) had recurrence of pulmonary embolism (relative risk, 0.27 [CI, 0.09 to 0.78]); 3 of 58 patients receiving high-dose danaparoid (5%) and 6 of 54 patients receiving unfractionated 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 results suggest that high-dose danaparoid is safer and more effective than unfractionated heparin for the treatment of venous thromboembolism.