Diana M. Sobieraj, PharmD; Soyon Lee, PharmD; Craig I. Coleman, PharmD; Vanita Tongbram, MBBS, MPH; Wendy Chen, PharmD; Jennifer Colby, PharmD; Jeffrey Kluger, MD; Sagar Makanji, PharmD; Ajibade O. Ashaye, MD, MPH; C. Michael White, PharmD
Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank the members of the key informant and technical expert panel for their contribution and expertise in the development of the key questions and protocol for this review: Yngve Falck-Ytter, MD, Case Western Reserve University School of Medicine, Cleveland, Ohio; Charles W. Francis, MD, University of Rochester School of Medicine, Rochester, New York; Joshua J. Jacobs, MD, Rush Medical College, Chicago, Illinois; J. Samuel Pope, MD, Hartford Hospital, Hartford, Connecticut; and Sandra Zelman Lewis, PhD, American College of Chest Physicians, Northbrook, Illinois. These individuals are not directly responsible for the final content, interpretation, or conclusions of this article.
Grant Support: By the University of Connecticut/Hartford Hospital Evidence-based Practice Center (contract 290-2007-10067-I with the Agency for Healthcare Research and Quality).
Potential Conflicts of Interest: Dr. Coleman: Grants/grants pending (money to institution): Janssen Pharmaceuticals; Consulting fee or honorarium: Janssen Pharmaceuticals; Consultancy: Acorda Therapeutics. Dr. Kluger: Payment for lectures including service on speakers bureaus: Janssen Pharmaceuticals. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2593.
Requests for Single Reprints: C. Michael White, PharmD, Department of Pharmacy, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102; e-mail, mailto:firstname.lastname@example.org.
Current Author Addresses: Drs. Sobieraj, Lee, Coleman, Chen, Makanji, and White: Department of Pharmacy, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102.
Dr. Tongbram: Oxford Outcomes/ICON Plc, 161 Madison Avenue, Suite 205, Morristown, NJ, 07960.
Dr. Colby: Institute for Clinical and Economic Review, 101 Merrimac Street, 3rd Floor, Boston, MA 02114.
Dr. Kluger: Department of Cardiology, Hartford Hospital, 80 Seymour Street, Hartford CT 06102.
Dr. Ashaye: Evidence Review & Synthesis, United BioSource Corporation, 430 Bedford Street, Lexington, MA 02420.
Author Contributions: Conception and design: D.M. Sobieraj, C.I. Coleman, V. Tongbram, C.M. White.
Analysis and interpretation of the data: D.M. Sobieraj, S. Lee, C.I. Coleman, V. Tongbram, J. Kluger, A.O. Ashaye, C.M. White.
Drafting of the article: D.M. Sobieraj, S. Lee, C.I. Coleman, V. Tongbram, C.M. White.
Critical revision of the article for important intellectual content: D.M. Sobieraj, S. Lee, C.I. Coleman, V. Tongbram, J. Kluger, C.M. White.
Final approval of the article: D.M. Sobieraj, S. Lee, C.I. Coleman, V. Tongbram, J. Colby, J. Kluger, A.O. Ashaye, C.M. White.
Provision of study materials or patients: D.M. Sobieraj, S. Lee.
Statistical expertise: D.M. Sobieraj, S. Lee, C.I. Coleman, V. Tongbram.
Obtaining of funding: D.M. Sobieraj, C.I. Coleman, J. Kluger, C.M. White.
Administrative, technical, or logistic support: D.M. Sobieraj, S. Lee, C.I. Coleman, V. Tongbram, J. Colby, S. Makanji, C.M. White.
Collection and assembly of data: D.M. Sobieraj, S. Lee, V. Tongbram, W. Chen, J. Colby, S. Makanji, A.O. Ashaye, C.M. White.
The optimal duration of thromboprophylaxis after major orthopedic surgery is unclear.
To compare the benefits and harms of prolonged versus standard-duration thromboprophylaxis after major orthopedic surgery in adults.
Cochrane Central Register of Controlled Trials and Scopus from 1980 to July 2011 and MEDLINE from 1980 through November 2011, without language restrictions.
Randomized trials reporting thromboembolic or bleeding outcomes that compared prolonged (≥21 days) with standard-duration (7 to 10 days) thromboprophylaxis.
Two independent reviewers abstracted data and rated study quality and strength of evidence.
Eight randomized, controlled trials (3 good-quality and 5 fair-quality) met the inclusion criteria. High-strength evidence showed that compared with standard-duration therapy, prolonged prophylaxis resulted in fewer cases of pulmonary embolism (PE) (5 trials; odds ratio [OR], 0.14 [95% CI, 0.04 to 0.47]; absolute risk reduction [ARR], 0.8%), asymptomatic deep venous thrombosis (DVT) (4 trials; relative risk [RR], 0.48 [CI, 0.31 to 0.75]; ARR, 5.8%), symptomatic DVT (4 trials; OR, 0.36 [CI, 0.16 to 0.81]; ARR, 1.5%), and proximal DVT (6 trials; RR, 0.29 [CI, 0.16 to 0.52]; ARR, 7.1%). Moderate-strength evidence showed fewer symptomatic objectively confirmed episodes of venous thromboembolism (4 trials; RR, 0.38 [CI, 0.19 to 0.77]; ARR, 5.7%), nonfatal PE (4 trials; OR, 0.13 [CI, 0.03 to 0.54]; ARR, 0.7%), and DVT (7 trials; RR, 0.37 [CI, 0.21 to 0.64]; ARR, 12.1%) with prolonged prophylaxis. High-strength evidence showed more minor bleeding events with prolonged prophylaxis (OR, 2.44 [CI, 1.41 to 4.20]; absolute risk increase, 6.3%), and insufficient evidence from 1 trial on hip fracture surgery suggested more surgical-site bleeding events (OR, 7.55 [CI, 1.51 to 37.64]) with prolonged prophylaxis.
Data relevant to knee replacement or hip fracture surgery were scant and insufficient. Most trials had few events; the strength of evidence ratings that were used may not adequately capture uncertainty in such situations.
Prolonged prophylaxis decreases the risk for venous thromboembolism, PE, and DVT while increasing the risk for minor bleeding in patients undergoing total hip replacement.
Agency for Healthcare Research and Quality.
Sobieraj DM, Lee S, Coleman CI, et al. Prolonged Versus Standard-Duration Venous Thromboprophylaxis in Major Orthopedic Surgery: A Systematic Review. Ann Intern Med. 2012;156:720–727. doi: 10.7326/0003-4819-156-10-201205150-00423
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Published: Ann Intern Med. 2012;156(10):720-727.
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