A post-marketing assessment of major bleeding in total hip and total knee replacement surgery patients receiving rivaroxaban

Abstract

Background: Rivaroxaban is a novel oral anticoagulant indicated for prophylaxis against deep vein thrombosis and pulmonary embolism in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery.

Objective: To evaluate major bleeding (MB) in THR/TKR patients receiving post-operative rivaroxaban.

Methods: Electronic medical records of nearly 10 million US Department of Defense (DoD) beneficiaries were queried from 1 January 2013 through 30 June 2015. Using the validated Cunningham case-finding algorithm, post-surgical MB events in rivaroxaban users were identified and analyzed. The incidence of MB was determined, and descriptive statistics were used to compare patient characteristics and other covariates in those with and without MB. Two additional methods were used to explore and identify bleeding cases that were not considered MB events per the study case-finding algorithm.

Results: A total of 12,429 patients received THR and/or TKR surgery, and were post-operatively prescribed rivaroxaban. Nine patients had MB, yielding an incidence proportion of 0.07% (95% CI 0.02–0.13). The alternative case-finding methods found bleeding incidences of 0.46% and 0.21%, though it is not clear whether these are clinical MB cases, since the alternative methods were not validated.

Conclusions: The incidence of MB in this retrospective analysis is lower than that observed in the clinical trials of rivaroxaban. Whether this is due to lower real-world MB rates or challenges with case-finding algorithms is unclear.

Keywords:

• rivaroxaban
• bleeding
• thromboembolism
• arthroplasty
• thromboprophylaxis

Transparency

Declaration of funding

This study is funded by Janssen Scientific Affairs LLC and Bayer HealthCare.

Author contributions: The current analysis was primarily conceived and designed by Z.Y. and L.M.K. N.S. conducted the data retrievals and data analyses. S.T. is the Principal Investigator of the ongoing Post-Marketing Safety Surveillance study. K.P.H. developed the initial draft, and L.M.K., A.G.G.T., S.T., W.F.P., Z.Y., and M.P. contributed substantially to each revision and provided clinician oversight to the material. All authors (L.M.K., A.G.G.T., S.T., W.F.P., Z.Y., N.S., K.P.H., and M.P.) contributed to each revision and the interpretation of the results, and approved the final draft. All authors agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

L.M.K. has disclosed that he is a consultant for Janssen Pharmaceuticals. A.G.G.T. has disclosed that he is a consultant for Bayer and Janssen. CAPT S.T. has disclosed that she is a military service member. This work was prepared as part of her official duties, and she has no conflicts of interest to disclose. W.F.P. has disclosed that he has received research grants from Abbott, Alere, Banyan, Cardiorentis, Janssen, Portola, Pfizer, Roche, The Medicines Company and ZS Pharma; he consults for Alere, Cardiorentis, Ischemia Care, Janssen, Phillips, Portola, Prevencio, The Medicines Company, and ZS Pharma, and has ownership interests in Comprehensive Research Associates LLC and Emergencies in Medicine LLC. Z.Y. has disclosed that he is a salaried employee of Janssen Research & Development LLC, and owns stocks of Johnson & Johnson. N.S. has disclosed that he is an employee of Health ResearchTx LLC, which has a business relationship with Janssen. K.P.H. has disclosed that she has received professional fees for medical writing from Health ResearchTx LLC, which has a business relationship with Janssen. M.P. has disclosed that he has received grants from Heart Flow Technologies, Janssen, Johnson & Johnson, AstraZeneca, the National Heart Lung and Blood Institute, and the Agency for Healthcare Research and Quality; he has also received personal fees from Astra Zeneca, Bayer, and Otsuka.

Acknowledgements

The authors would like to thank the Navy and Marine Corps Public Health Center for its support during the conduct of the study.

Disclaimer: The views expressed in this manuscript are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense or the United States Government.

Copyright notice: CAPT Sally Tamayo is a military service member. This work was prepared as part of her official duties. Title 17 USC 105 provides that “Copyright protection under this title is not available for any work of the United States Government”. Title 17 USC 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person’s official duties.

Previous presentation: Preliminary results of the analyses reported in this paper were previously presented in abstract form at the 2014 THSNA conference and the 2014 ACEP conference (both held in Chicago, Illinois).