What is the role of factor Xa inhibitors in deep venous thrombosis (DVT) prophylaxis for patients undergoing orthopedic surgery?

Answer

Direct oral anticoagulants (DOACs) are increasingly being used as alternatives to LMWH for thromboprophylaxis in patients undergoing orthopedic surgery. A meta-analysis by Haykal et al found DOACs to be associated with significant reductions in major VTE and DVT as compared with LMWH.^[42]

Large phase III clinical trials have described the use of the factor Xa inhibitor rivaroxaban for prevention of thromboembolism following total knee or total hip arthroplasty. Rivaroxaban is administered once daily and has shown significant superiority in preventing DVT, nonfatal PE, or death compared with SC enoxaparin following arthroplastic surgery. It was the first orally active direct inhibitor of coagulation factor Xa approved by the US Food and Drug Administration (FDA) and is indicated for prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.^{[43, 44, 45, 46, 47, 48]}

Rivaroxaban was compared with enoxaparin for acute DVT. Efficacy showed noninferiority to enoxaparin for short-term use. When used as continued treatment, rivaroxaban had superior efficacy (P< .001) compared with placebo. A study comparing rivaroxaban to warfarin for long-term efficacy is warranted.^[49] Rivaroxaban was found to be equivalent to enoxaparin/vitamin K antagonist in the treatment of established DVT, also without an increase in bleeding complications.

Another factor Xa inhibitor, apixaban, was approved by the FDA in March 2014 for postoperative prophylaxis of DVT/PE following hip or knee arthroplasty. Apixaban compared favorably with enoxaparin in the prevention of DVT after hip or knee replacement without increased bleeding.^{[50, 51]}

The factor Xa inhibitor edoxaban was approved by the FDA in January 2015 for treatment of DVT and PE in patients who have been initially treated with a parenteral anticoagulant for 5-10 days. It has also been used for prophylaxis.^[52]

Betrixaban, another factor Xa inhibitor, was approved by the FDA in June 2017. It is indicated for prophylaxis of VTE in adults hospitalized for acute medical illness who are at risk for thromboembolic complications owing to moderate or severe restricted mobility and other risk factors that may cause VTE.

For more information, see Deep Venous Thrombosis and Pulmonary Embolism.

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Comparison of binding sites for standard heparin and low-molecular-weight heparin.
Time course of deep venous thrombosis risk.

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Author

David A Forsh, MD Chief, Orthopedic Trauma Surgery, Assistant Professor, Department of Orthopedic Surgery, Icahn School of Medicine at Mount Sinai

David A Forsh, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Orthopaedic Trauma Association, AO North America

Disclosure: Nothing to disclose.

Chief Editor

Vinod K Panchbhavi, MD, FACS, FAOA, FABOS, FAAOS Professor of Orthopedic Surgery, Chief, Division of Foot and Ankle Surgery, Director, Foot and Ankle Fellowship Program, Department of Orthopedic Surgery, University of Texas Medical Branch School of Medicine

Vinod K Panchbhavi, MD, FACS, FAOA, FABOS, FAAOS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, American Orthopaedic Foot and Ankle Society, Orthopaedic Trauma Association, Texas Orthopaedic Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Styker.

Acknowledgements

Paul E Di Cesare, MD, FACS Professor, Department of Orthopedic Sugery, University of California, Davis, School of Medicine

Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Sigma Xi

Disclosure: Stryker Consulting fee Consulting; Smith & Nephew Consulting fee Consulting

Robert S Ennis, MD, FACS Associate Professor, Department of Orthopedic Surgery, University of Miami School of Medicine; President, OrthoMed Consulting Services, Inc

Robert S Ennis, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Florida Orthopaedic Society

Disclosure: Nothing to disclose.

Miguel A Schmitz, MD Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic

Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, and North American Spine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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