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Prevention of Venous Thromboembolic Disease Following Primary Total Knee Arthroplasty A Randomized, Multicenter, Open-Label, Parallel-Group Comparison of Enoxaparin and Warfarin
R. H. Fitzgerald, MD, Jr; T. E. Spiro, MD; A. A. Trowbridge, MD; G. A. GardinerJr., MD; T. L. Whitsett, MD; M. B. O’Connell, PharmD; J. A. Ohar, MD; T. R. Young, DO, for the Enoxaparin Clinical Trial Group
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R.H. Fitzgerald Jr., MD Department of Orthopaedic Surgery, Silverstein Pavilion, Hospital of the University of Pennsylvania, 3400 Spruce Street, Second Floor, Philadelphia, PA 19104
T.E. Spiro, MD Cardiovascular Therapeutic Area, European Operations Center, Aventis Pharma S.A., 20 avenue Raymond Aron, 92165 Antony, France. E-mail address: theodore.spiro@aventis.com
A.A. Trowbridge, MD Division of Hematology, Department of Internal Medicine, Scott and White Clinic, Texas A and M University College of Medicine, 2401 South 31st Street, Temple, TX 76508
G.A. Gardiner Jr., MD Department of Radiology, Gibbon Building, Thomas Jefferson University Hospital, 111 South 11th Street, Philadelphia, PA 19107
T.L. Whitsett, MD Section of Cardiovascular Medicine, South Pavilion, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
M.B. O’Connell, PharmD Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, MN 55455
J.A. Ohar, MD Division of Pulmonary Medicine, St. Louis University Medical Center, St. Louis, MO 63110
T.R. Young, DO Department of Orthopaedic Surgery, Medical College of Georgia, Augusta, GA 30912
Funds were received in total or partial support of the research or clinical study presented in this article. The funding source was a grant from Aventis Pharmaceuticals, Incorporated, Bridgewater, New Jersey (formerly known as Rhône-Poulenc Rorer Pharmaceuticals, Incorporated, Collegeville, Pennsylvania). Benefits were directed either to a research fund, foundation, educational institution, or other nonprofit organization with which one or more of the authors is associated or were directed to a commercial institution such as a university hospital or a major medical center with which one or more of the authors is associated. T.E. Spiro is a full-time employee of Aventis Pharma, S.A., and holds stocks and options in this company.

J Bone Joint Surg Am, 2001 Jun 01;83(6):900-906
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Abstract

Background: Patients treated with total knee arthroplasty are at high risk for the development of venous thromboembolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin.

Methods: Three hundred and forty-nine patients were included in a prospective, randomized, multicenter, open-label, parallel-group clinical trial. Treatment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was initiated during the immediate postoperative period, within eight hours after the surgery, and was continued for four to fourteen days. Venous thromboembolism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonography, or symptomatic pulmonary embolism confirmed by a positive lung scan or pulmonary angiography.

Results: In the all-treated-patients group, eighty (45%) of the 176 warfarin-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significantly fewer (p = 0.0001) enoxaparin-treated patients (forty-four of 173; 25%): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-treated patients also had a significantly lower prevalence of proximal deep-vein thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3.19) with warfarin than they were with enoxaparin. Major hemorrhage occurred in four warfarin-treated patients and nine enoxaparin-treated patients; with the numbers available, this difference was not significant (p = 0.17). Clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patients (p = 0.15).

Conclusions: A fixed 30-mg subcutaneous dose of enoxaparin, administered twice daily, with the first dose administered within eight hours after the completion of surgery, was significantly more effective than adjusted-dose warfarin in reducing the occurrence of asymptomatic venous thromboembolism, including proximal deep-vein thrombosis, in patients undergoing total knee arthroplasty. With the numbers available, there was no significant difference between groups with regard to the occurrence of major hemorrhagic complications; however, the rate of overall hemorrhagic complications was higher in the enoxaparin group.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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