Ignacio Neumann, MD; Gabriel Rada, MD; Juan Carlos Claro, MD; Alonso Carrasco-Labra, DDS; Kristian Thorlund, PhD; Elie A. Akl, MD, MPH, PhD; Shannon M. Bates, MD, MSc; Gordon H. Guyatt, MD, MSc
Acknowledgment: The authors thank Jo-Anne Petropoulos for her help in developing the search strategy and the authors of the trials who kindly provided additional data.
Potential Conflicts of Interest: Dr. Guyatt: Consultancy (money to institution): Bristol-Myers Squibb; Grants/grants pending (money to institution): Canadian Institutes of Health Research. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2601.
Requests for Single Reprints: Ignacio Neumann, MD, McMaster University Health Sciences Centre, Clinical Epidemiology & Biostatistics, Room 2C12, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada; e-mail, mailto:firstname.lastname@example.org.
Current Author Addresses: Drs. Neumann, Carrasco-Labra, Thorlund, and Guyatt: McMaster University Health Sciences Centre, Clinical Epidemiology & Biostatistics, Room 2C12, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Drs. Rada and Claro: Evidence Based Health Care Program, Pontificia Universidad Católica de Chile, Lira 63, Santiago, Chile.
Dr. Akl: Department of Medicine, State University of New York at Buffalo, 462 Grider Street, ECMC-CC 142, Buffalo, NY 14215.
Dr. Bates: Department of Medicine, McMaster University Health Sciences Centre, Room 3W11, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada.
Author Contributions: Conception and design: I. Neumann, J.C. Claro, G.H. Guyatt.
Analysis and interpretation of the data: I. Neumann, K. Thorlund, E.A. Akl, G.H. Guyatt.
Drafting of the article: I. Neumann, G.H. Guyatt.
Critical revision of the article for important intellectual content: I. Neumann, G. Rada, J.C. Claro, K. Thorlund, E.A. Akl, S.M. Bates, G.H. Guyatt.
Final approval of the article: I. Neumann, G. Rada, J.C. Claro, A. Carrasco-Labra, E.A. Akl, S.M. Bates, G.H. Guyatt.
Statistical expertise: K. Thorlund.
Administrative, technical, or logistic support: I. Neumann.
Collection and assembly of data: I. Neumann, G. Rada, J.C. Claro, A. Carrasco-Labra.
Thromboembolic disease is the most frequent medical complication of arthroplasty.
To evaluate the benefits and harms of oral direct factor Xa inhibitors versus low-molecular-weight heparin (LMWH) in patients undergoing total hip or knee replacement.
MEDLINE (1966 to December 2011), EMBASE (1980 to December 2011), and the Cochrane Central Register of Controlled Trials (up to December 2011), without language restrictions. References of reviews and abstracts of conferences were hand-searched.
Randomized trials in patients undergoing hip or knee replacement that evaluated factor Xa inhibitors versus LMWH.
Two reviewers independently evaluated eligibility, abstracted the data, and assessed risk for bias.
In 22 trials, high-quality evidence indicated that the absolute effect of factor Xa inhibitors and LMWH does not differ in terms of all-cause mortality (risk difference, 0 fewer deaths per 1000 patients [95% CI, 2 fewer to 1 more death]) or nonfatal pulmonary embolism (risk difference, 0 fewer events per 1000 patients [CI, 1 fewer to 2 more events]). Factor Xa inhibitors can prevent 4 instances of symptomatic deep venous thrombosis per 1000 treated patients (CI, 3 to 6 fewer events; high-quality evidence) but may increase major bleeding by 2 more events per 1000 patients (CI, 0 to 4 more events; moderate-quality evidence). High, but not lower, doses of oral factor Xa inhibitors increased bleeding compared with LMWH.
Most trials did not report outcome data for a substantial proportion of the patients. In 9 trials, the follow-up period was 14 days or less.
Compared with LMWH, lower doses of oral factor Xa inhibitors can achieve a small absolute risk reduction in symptomatic deep venous thrombosis without increasing bleeding.
Ignacio Neumann, Gabriel Rada, Juan Carlos Claro, Alonso Carrasco-Labra, Kristian Thorlund, Elie A. Akl, et al. Oral Direct Factor Xa Inhibitors Versus Low-Molecular-Weight Heparin to Prevent Venous Thromboembolism in Patients Undergoing Total Hip or Knee Replacement: A Systematic Review and Meta-analysis. Ann Intern Med. 2012;156:710–719. doi: 10.7326/0003-4819-156-10-201205150-00421
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Published: Ann Intern Med. 2012;156(10):710-719.
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