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Comparative Effectiveness of New Oral Anticoagulants and Standard Thromboprophylaxis in Patients Having Total Hip or Knee Replacement: A Systematic Review

Soheir S. Adam, MD; Jennifer R. McDuffie, PhD; Paul F. Lachiewicz, MD; Thomas L. Ortel, MD, PhD; and John W. Williams Jr., MD, MHS
[+] Article, Author, and Disclosure Information

From Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, North Carolina; and King Abdulaziz University, Jeddah, Saudi Arabia.

Acknowledgment: The authors thank Connie Schardt for help with the literature search and retrieval and Liz Wing for editorial assistance.

Grant Support: By U.S. Department of Veterans Affairs Office of Research and Development Quality Enhancement Research Initiative (VA-ESP Project 09-010).

Potential Conflicts of Interest: Dr. McDuffie: Grant (money to institution): U.S. Department of Veterans Affairs Evidence-based Synthesis Program. Dr. Lachiewicz: Grants/grants pending: Zimmer. Other: Cadence; Journal of Arthroplasty; personal fees from Cadence, Allergan, Gerson Lehrman Group, Global Guidepoint Advisors, Innomed. Dr. Ortel: Consultancy: Instrumentation Laboratory, Bayer, Boehringer Ingelheim, CSL Behring; Grants/grants pending: Eisai, Pfizer, GlaxoSmithKline, Daiichi Sankyo. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0383.

Requests for Single Reprints: Soheir S. Adam, MD, Duke University Medical Center, Department of Medicine, Box 3939, Durham, NC 27710; e-mail, soheir.adam@duke.edu.

Current Author Addresses: Dr. Adam: Department of Medicine, Duke University Medical Center, Box 3939, Durham, NC 27710.

Dr. McDuffie: Durham Veterans Affairs Medical Center, 411 West Chapel Hill Street, Suite 600, Durham, NC 27701.

Dr. Lachiewicz: Department of Surgery, Durham Veteran's Affairs Hospital, Fulton Street, Durham, NC 27701.

Dr. Ortel: Department of Medicine, Duke University Medical Center, DUHS Box 3422, Durham, NC 27710.

Dr. Williams: Durham Veterans Affairs Medical Center, 411 West Chapel Hill Street, Suite 500, Durham, NC 27701.

Author Contributions: Conception and design: S.S. Adam, J.R. McDuffie, T.L. Ortel, J.W. Williams Jr.

Analysis and interpretation of the data: S.S. Adam, J.R. McDuffie, P.F. Lachiewicz, T.L. Ortel, J.W. Williams Jr.

Drafting of the article: S.S. Adam, J.R. McDuffie.

Critical revision of the article for important intellectual content: S.S. Adam, J.R. McDuffie, P.F. Lachiewicz, T.L. Ortel, J.W. Williams Jr.

Final approval of the article: S.S. Adam, J.R. McDuffie, P.F. Lachiewicz, T.L. Ortel, J.W. Williams Jr.

Provision of study materials or patients: J.R. McDuffie.

Obtaining of funding: J.W. Williams Jr.

Administrative, technical, or logistic support: J.R. McDuffie.

Collection and assembly of data: S.S. Adam, J.W. Williams Jr.

Ann Intern Med. 2013;159(4):275-284. doi:10.7326/0003-4819-159-4-201308200-00008
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Background: Pharmacologic thromboprophylaxis reduces the risk for venous thromboembolism after total hip replacement (THR) or total knee replacement (TKR). New oral anticoagulants (NOACs), including direct thrombin inhibitors and factor Xa inhibitors, are emerging options for thromboprophylaxis after these procedures.

Purpose: To compare the benefits and risks of NOACs versus standard thromboprophylaxis for adults having THR or TKR.

Data Sources: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2009 through March 2013.

Study Selection: English-language systematic reviews.

Data Extraction: Two independent reviewers abstracted data and rated study quality and strength of evidence.

Data Synthesis: Six good-quality systematic reviews compared NOACs with low-molecular-weight heparin (LMWH) for thromboprophylaxis after THR or TKR. Risk for symptomatic deep venous thrombosis, but not risk for death or nonfatal pulmonary embolism, was reduced with factor Xa inhibitors compared with LMWH (4 fewer events per 1000 patients). Conversely, the risk for major bleeding increased (2 more events per 1000 patients). Outcomes of dabigatran did not significantly differ from those of LMWH. Indirect evaluation of NOACs by common comparison with LMWH showed nonsignificantly reduced risks for venous thromboembolism with rivaroxaban compared with dabigatran (risk ratio [RR], 0.68 [95% CI, 0.21 to 2.23]) and apixaban (RR, 0.59 [CI, 0.26 to 1.33]) but increased major bleeding. New oral anticoagulants have not been compared with warfarin, aspirin, or unfractionated heparin.

Limitations: Head-to-head comparisons among NOACs were not available. Efficacy is uncertain in routine clinical practice.

Conclusion: New oral anticoagulants are effective for thromboprophylaxis after THR and TKR. Their clinical benefits over LMWH are marginal and offset by increased risk for major bleeding.

Primary Funding Source: U.S. Department of Veterans Affairs.


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Figure 1.

Summary of evidence search and selection.

KQ = key question; SR = systematic review.

* Search results for SRs from PubMed (117 references), EMBASE (42 references), Cochrane (3 references), a previous database (14 references), and manual searches (6 references) were combined.

† 20 were used to write the background sections.

‡ Cao YB, Zhang JD, Shen H, et al (Eur J Clin Pharmacol. 2010;66:1099-108); Huang J, Cao Y, Liao C, et al (Thromb Haemost. 2011;105:245-53); and Turun S, Banghua L, Yuan Y, et al (Thromb Res. 2011;127:525-34).

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Figure 2.

Effects of new oral anticoagulants compared with LMWH, by main outcomes and drug class.

DVT = deep venous thrombosis; FXa = factor Xa; LMWH = low-molecular-weight heparin; OR = odds ratio; PE = pulmonary embolism; RR = risk ratio.

* Results from reference 20.

† Up to 10 wk.

‡ Results from reference 17.

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