1. Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement
- Author
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Eriksson, B. I., Borris, L., Dahl, O. E., Haas, S., Huisman, M. V., Kakkar, A. K., Misselwitz, F., Kalebo, P., Breyer, H. -G., Bounameaux, H., Leizorovicz, A., Angeras, U., Falk, A., Prins, M., Zachrisson, B., Eriksson, H., Sandgren, G., Wallin, J., Engel, A., Hochreiter, J., Niessner, H., Driesen, R., Horlyck, E., Jorgensen, P. S., Lassen, M., Delecroix, M., Hayek, E., Le Pelley, E., Birkner, W., Fritsche, H. -M., Gunther, K. -P., Halder, A., Kleinfeld, F., Kurth, A., Mouret, P., Brenner, B., Dekel, S., Halperin, N., Martinovich, U., Ageno, W., Fraschini, G., Lodigiani, C., Parise, P., Silingardi, M., Slappendel, R., van der Vis, H., Verburg, A., Aarseth, O., Hovick, O., Hovind, H., Bednarek, A., Blancha, J., Kwiatkowski, K., Mazurkiewicz, S., Niedzwiedski, T., Skowronski, J., Castellet, E., Gomar, F., Granero, X., Peidro, L., Edshage, B., Lind, S., Wykman, A., and Cohen, A.
- Subjects
Male ,medicine.drug_mechanism_of_action ,medicine.medical_treatment ,Deep vein ,Arthroplasty, Replacement, Hip ,Knee replacement ,law.invention ,Postoperative Complications ,Randomized controlled trial ,Rivaroxaban ,law ,Aged, 80 and over ,Venous Thrombosis ,medicine.diagnostic_test ,Total hip replacement ,Hematology ,Middle Aged ,Thrombosis ,Pulmonary embolism ,Direct Factor Xa inhibitor ,medicine.anatomical_structure ,Anesthesia ,Female ,Venous thromboembolism ,medicine.drug ,Adult ,medicine.medical_specialty ,Morpholines ,Factor Xa Inhibitor ,Venography ,Hemorrhage ,Thiophenes ,Oral anticoagulant ,Prophylaxis ,Double-Blind Method ,Thromboembolism ,medicine ,Humans ,Enoxaparin ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Anticoagulants ,medicine.disease ,Surgery ,business ,Pulmonary Embolism ,Factor Xa Inhibitors - Abstract
Summary. Background: Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants. Objectives: To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor – BAY 59-7939 – relative to enoxaparin in patients undergoing elective total hip replacement. Methods: In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6–8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5–9 days after surgery. Results: Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose–response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin. Conclusions: When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5–10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.
- Published
- 2006