USE OF HIRULOG IN THE PREVENTION OF VENOUS THROMBOSIS AFTER MAJOR HIPOR KNEE SURGERY

Background The study objective was to determine whether Hirulog, a dir ect thrombin inhibitor, has potential efficacy and safety in the preve ntion of deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label, dose-escalating design was used to study 222 unselected pa tients undergoing major hip or knee surgery in tertiary-care, universi ty-affiliate hospitals. Methods and Results Subcutaneous Hirulog was i nitiated postoperatively. Patients were evaluated for bleeding and sym ptomatic pulmonary embolism, and mandatory bilateral venography was pe rformed before discharge. Dose escalations were made on the basis of o bserved rates of bleeding and venous thrombosis. There were five dosag e regimens used: 0.3 mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1 .0 mg/kg every 12 hours for 3 days followed by 0.6 mg/kg every 12 hour s for up to 11 days, 1.0 mg/kg every 12 hours, and 1.0 mg/kg every 8 h ours. One hundred seventy-seven patients who had technically adequate bilateral venography or objectively documented pulmonary embolism were included in the primary analysis of efficacy. The highest dosage regi men (1.0 mg/kg every 8 hours) provided the lowest rates of total DVT ( 17%) and proximal DVT (2%), both of which were significantly lower (P= .010 and P=.023, respectively) than the pooled rates of total (43%) an d proximal (20%) DVT seen with the first four regimens. Bleeding rates were low (<5%) with all regimens. Conclusions This study demonstrates that 1.0 mg/kg Hirulog every 8 hours started postoperatively is poten tially efficacious and safe for the prevention of DVT after major hip or knee surgery.