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Factors associated with non-use and sub-target dosing of medical therapy for heart failure with reduced ejection fraction

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Abstract

In clinical practice, many patients with heart failure with reduced ejection fraction (HFrEF) are either not prescribed guideline-directed medical therapies for which they are eligible or are prescribed therapies at sub-target doses. The objective of this study was to examine the factors associated with not receiving guideline-directed medical therapies or receiving sub-target doses. We conducted a systematic review of articles published between January 2014 and May 2019 that described dosing patterns and factors associated with non-use and sub-target dosing of HFrEF therapies in clinical practice. Thirty-seven studies were included. The percentages of patients reaching target doses for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists ranged from 4 to 55%, 11 to 87%, 4 to 60%, and 22 to 80%, respectively. Older age and worsening renal function were associated with non-use and sub-target dosing, lower body mass index was commonly associated with non-use, and hyperkalemia and hypotension were commonly associated with sub-target dosing. In conclusion, several common patient characteristics are associated with non-use and sub-target dosing of medical therapy for HFrEF. These high-risk groups are in particular need of further studies to improve implementation of available medications and to define the role of novel therapies.

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Acknowledgments

The authors thank Melissa Stauffer and Anna Kaufman in collaboration with ScribCo for medical writing assistance.

Funding

This study was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Authors and Affiliations

  1. Duke Clinical Research Institute, Durham, NC, USA

    Stephen J. Greene

  2. Division of Cardiology, Duke University School of Medicine, Durham, NC, USA

    Stephen J. Greene

  3. Merck & Co., Inc, Kenilworth, NJ, USA

    Xi Tan & Mei Yang

  4. Pharmerit – an OPEN Health Company, Newton, MA, USA

    Yu-Chen Yeh, Mark Bernauer & Omer Zaidi

  5. Department of Medicine, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA

    Javed Butler

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Contributions

All authors contributed to the conception and design of the study. Yu-Chen Yeh, Mark Bernauer, and Omer Zaidi contributed to acquisition of the data. All coauthors contributed to the analysis and interpretation of the data. Stephen J. Greene, Xi Tan, and Javed Butler contributed to drafting of the manuscript. All authors contributed to critically reviewing or revising the manuscript for important intellectual content. All authors gave final approval of the submitted manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Javed Butler.

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Conflict of interests

Stephen J. Greene has received a Heart Failure Society of America/ Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; has received research support from the American Heart Association, Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; has served on advisory boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. Xi Tan and Mei Yang are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and stockholders of Merck & Co., Inc., Kenilworth, NJ, USA. Yu-Chen Yeh, Mark Bernauer, and Omer Zaidi are employees of Pharmerit, which received research support from Merck & Co., Inc. to conduct the study. Javed Butler serves as a consultant to Abbott, Array, Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, CVRx, Eli Lilly, G3 Pharma, Impulse Dynamics, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Sequana Medical, V-Wave Limited, and Vifor.

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Greene, S.J., Tan, X., Yeh, YC. et al. Factors associated with non-use and sub-target dosing of medical therapy for heart failure with reduced ejection fraction. Heart Fail Rev 27, 741–753 (2022). https://doi.org/10.1007/s10741-021-10077-x

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