Ardeparin Sodium for Extended Out-of-Hospital Prophylaxis against Venous Thromboembolism after Total Hip or Knee Replacement

A Randomized, Double-Blind, Placebo-Controlled Trial

  1. John A. Heit, MD;
  2. C. Gregory Elliott, MD;
  3. Arthur A. Trowbridge, MD;
  4. Bernard F. Morrey, MD;
  5. Michael Gent, DSc;
  6. Jack Hirsh, MD; and
  7. for the Ardeparin Arthroplasty Study Group*
  1. From the Mayo Clinic and Foundation, Rochester, Minnesota; LDS Hospital and the University of Utah School of Medicine, Salt Lake City, Utah; Texas A&M University College of Medicine, Temple, Texas; and McMaster University, Hamilton, Ontario, Canada.

    Abstract

    Background: The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain.

    Objective: To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium).

    Design: Randomized, double-blind, placebo-controlled trial.

    Setting: 33 community, university, or university-affiliated hospitals.

    Patients: 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis.

    Intervention: Daily subcutaneous ardeparin (100 IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery.

    Measurements: Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery.

    Results: Patients who received ardeparin (n = 607) and those who received placebo (n = 588) did not differ significantly in the cumulative incidence of venous thromboembolism or death (9 cases [1.5%] compared with 12 cases [2.0%]; odds ratio, 0.7 [95% CI, 0.3 to 1.7]; P > 0.2; absolute difference, −0.56 percentage points [CI, −2.2 to 1.1 percentage points]) or major bleeding (2 cases [0.3%] compared with 3 cases [0.5%]).

    Conclusions: Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis, the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced by extended out-of-hospital ardeparin prophylaxis. Extended ardeparin use could provide a maximum 2.2–percentage point true reduction in such events. The benefit of extended ardeparin use is not clinically important for most patients. Future research should identify high-risk patients who would benefit most from extended prophylaxis.

    *For members of the Ardeparin Arthroplasty Study Group, see Appendix.

    Article and Author Information

    • Acknowledgments: The authors thank the surgical, nursing, pharmacy, and support staff at all the study sites. They also thank Dr. D. Scott Holloway and Ms. Joanne DiLiberto, Wyeth-Ayerst Research.

    • Grant Support: By Wyeth-Ayerst Research, Philadelphia, Pennsylvania.

    • Requests for Single Reprints: John A. Heit, MD, Hematology Research, Plummer 549, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

    • Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

    • Current Author Addresses: Dr. Heit: Hematology Research, Plummer 549, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

    • Dr. Elliott: LDS Hospital, University of Utah, Eighth Avenue and C Street, Salt Lake City, UT 84143.

    • Dr. Trowbridge: Texas A&M University, 2401 South 31st Street, Temple, TX 76508.

    • Dr. Morrey: Mayo Clinic, 200 First Street, SW, Rochester, MN 55905.

    • Drs. Gent and Hirsh: Hamilton Civic Hospitals Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.

    • Author Contributions: Conception and design: C.G. Elliott, B.F. Morrey, J.A. Heit, J. Hirsh.

    • Analysis and interpretation of the data: C.G. Elliott, A.A. Trowbridge, M. Gent, J.A. Heit, J. Hirsh.

    • Drafting of the article: A.A. Trowbridge, M. Gent, J.A. Heit, J. Hirsh.

    • Critical revision of the article for important intellectual content: C.G. Elliott, A.A. Trowbridge, M. Gent, J.A. Heit, J. Hirsh.

    • Final approval of the article: C.G. Elliott, A.A. Trowbridge, B.F. Morrey, J.A. Heit, J. Hirsh.

    • Provision of study materials or patients: C.G. Elliott, A.A. Trowbridge, J.A. Heit, B.F. Morrey.

    • Statistical expertise: M. Gent.

    • Administrative, technical, or logistic support: M. Gent.

    • Collection and assembly of data: C.G. Elliott, J.A. Heit.

    Summary for Patients

    • Summaries for Patients:Use of a New Form of the Blood Thinner Heparin Outside the Hospital To Prevent Blood Clots after Hip or Knee Replacement Ann Intern Med June 6, 2000 132:853
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    1. Ann Intern Med June 6, 2000 vol. 132 no. 11 853-861
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