In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction

Vishal N. Rao; Evan Murray; Javed Butler; Lauren B. Cooper; Zachary L. Cox; Mona Fiuzat; Jennifer B. Green; Jo Ann Lindenfeld; Darren K. McGuire; Michael E. Nassif; Cara O'Brien; Neha Pagidipati; Kavita Sharma; Muthiah Vaduganathan; Orly Vardeny; Gregg C. Fonarow; Robert J. Mentz; Stephen J. Greene

doi:10.1016/j.jacc.2021.08.064

In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction

Vishal N. Rao, Evan Murray, Javed Butler, Lauren B. Cooper, Zachary L. Cox, Mona Fiuzat, Jennifer B. Green, Jo Ann Lindenfeld, Darren K. McGuire, Michael E. Nassif, Cara O'Brien, Neha Pagidipati, Kavita Sharma, Muthiah Vaduganathan, Orly Vardeny, Gregg C. Fonarow, Robert J. Mentz, Stephen J. Greene

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Review article › peer-review

21 Scopus citations

Abstract

Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to the outpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications to the U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4 patients hospitalized for worsening heart failure die or are readmitted within 30 days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this population with the urgency it deserves.

Original language	English (US)
Pages (from-to)	2004-2012
Number of pages	9
Journal	Journal of the American College of Cardiology
Volume	78
Issue number	20
DOIs	https://doi.org/10.1016/j.jacc.2021.08.064
State	Published - Nov 16 2021

Bibliographical note

Funding Information:
This paper summarizes proceedings of an independently organized academic meeting supported by an unrestricted educational grant from AstraZeneca. AstraZeneca did not have any role in the design, interpretation, or submission of the paper’s content. Dr Rao has been supported by a National Institutes of Health (NIH) Training Grant (NIH 5T32HL069749-17). Dr Butler has served as a consultant for Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd., and Vifor. Dr Cooper has received consulting fees from AstraZeneca; and has received research support from Abbott. Dr Cox has received research support from AstraZeneca. Dr Green has received research support from Boehringer Ingelheim/Lilly, Merck, Roche and Sanofi/Lexicon; and has received consulting fees from AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, NovoNordisk, and Pfizer. Dr Lindenfeld has received research support from AstraZeneca, Sensible Medical, and Volumetrix; and has received consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Cytokinetics, Edwards Lifesciences, Impulse Dynamics, V-Wave, and Vifor. Dr McGuire has received honoraria for clinical trial leadership from Boehringer Ingelheim, Sanofi, AstraZeneca, Merck & Co, Pfizer, Novo Nordisk, Esperion, Lilly USA, Lexicon, and CSL Behring; and has received honoraria for consultancy from Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Applied Therapeutics, Metavant, Sanofi, Afimmune, and Lexicon. Dr Pagidipati has received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Regeneron, Sanofi, and Verily Life Sciences; and has received consulting fees from Boehringer Ingelheim, Eli Lilly, AstraZeneca, and Novo Nordisk. Dr Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, and Relypsa; has speaker engagements for Novartis; and has participated on clinical endpoint committees for studies sponsored by Galmed, Novartis, and NIH. Dr Fonarow served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck, and Novartis. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, and Windtree Therapeutics. Dr Greene has received research support from the Duke University Department of Medicine Chair’s Research Award, American Heart Association, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, and Pfizer; has served on advisory boards for Amgen, AstraZeneca, Bristol Myers Squibb, and Cytokinetics; and has served as a consultant for Amgen, Bayer, Bristol Myers Squibb, Merck, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation

Keywords

guideline-directed medical therapy
heart failure
in-hospital prescribing
medical therapy
sodium-glucose cotransporter-2 inhibitors

Publisher link

10.1016/j.jacc.2021.08.064

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Rao, V. N., Murray, E., Butler, J., Cooper, L. B., Cox, Z. L., Fiuzat, M., Green, J. B., Lindenfeld, J. A., McGuire, D. K., Nassif, M. E., O'Brien, C., Pagidipati, N., Sharma, K., Vaduganathan, M., Vardeny, O., Fonarow, G. C., Mentz, R. J., & Greene, S. J. (2021). In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction. Journal of the American College of Cardiology, 78(20), 2004-2012. https://doi.org/10.1016/j.jacc.2021.08.064

Rao, VN, Murray, E, Butler, J, Cooper, LB, Cox, ZL, Fiuzat, M, Green, JB, Lindenfeld, JA, McGuire, DK, Nassif, ME, O'Brien, C, Pagidipati, N, Sharma, K, Vaduganathan, M, Vardeny, O, Fonarow, GC, Mentz, RJ & Greene, SJ 2021, 'In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction', Journal of the American College of Cardiology, vol. 78, no. 20, pp. 2004-2012. https://doi.org/10.1016/j.jacc.2021.08.064

@article{2cc94bf02e4c45b0b8f04d383d2947f6,

title = "In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction",

abstract = "Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to the outpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications to the U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4 patients hospitalized for worsening heart failure die or are readmitted within 30 days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this population with the urgency it deserves.",

keywords = "guideline-directed medical therapy, heart failure, in-hospital prescribing, medical therapy, sodium-glucose cotransporter-2 inhibitors",

author = "Rao, {Vishal N.} and Evan Murray and Javed Butler and Cooper, {Lauren B.} and Cox, {Zachary L.} and Mona Fiuzat and Green, {Jennifer B.} and Lindenfeld, {Jo Ann} and McGuire, {Darren K.} and Nassif, {Michael E.} and Cara O'Brien and Neha Pagidipati and Kavita Sharma and Muthiah Vaduganathan and Orly Vardeny and Fonarow, {Gregg C.} and Mentz, {Robert J.} and Greene, {Stephen J.}",

note = "Funding Information: This paper summarizes proceedings of an independently organized academic meeting supported by an unrestricted educational grant from AstraZeneca. AstraZeneca did not have any role in the design, interpretation, or submission of the paper{\textquoteright}s content. Dr Rao has been supported by a National Institutes of Health (NIH) Training Grant (NIH 5T32HL069749-17). Dr Butler has served as a consultant for Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd., and Vifor. Dr Cooper has received consulting fees from AstraZeneca; and has received research support from Abbott. Dr Cox has received research support from AstraZeneca. Dr Green has received research support from Boehringer Ingelheim/Lilly, Merck, Roche and Sanofi/Lexicon; and has received consulting fees from AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, NovoNordisk, and Pfizer. Dr Lindenfeld has received research support from AstraZeneca, Sensible Medical, and Volumetrix; and has received consulting fees from Abbott, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Cytokinetics, Edwards Lifesciences, Impulse Dynamics, V-Wave, and Vifor. Dr McGuire has received honoraria for clinical trial leadership from Boehringer Ingelheim, Sanofi, AstraZeneca, Merck & Co, Pfizer, Novo Nordisk, Esperion, Lilly USA, Lexicon, and CSL Behring; and has received honoraria for consultancy from Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Applied Therapeutics, Metavant, Sanofi, Afimmune, and Lexicon. Dr Pagidipati has received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Regeneron, Sanofi, and Verily Life Sciences; and has received consulting fees from Boehringer Ingelheim, Eli Lilly, AstraZeneca, and Novo Nordisk. Dr Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, and Relypsa; has speaker engagements for Novartis; and has participated on clinical endpoint committees for studies sponsored by Galmed, Novartis, and NIH. Dr Fonarow served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Janssen, Medtronic, Merck, and Novartis. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, and Windtree Therapeutics. Dr Greene has received research support from the Duke University Department of Medicine Chair{\textquoteright}s Research Award, American Heart Association, Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, and Pfizer; has served on advisory boards for Amgen, AstraZeneca, Bristol Myers Squibb, and Cytokinetics; and has served as a consultant for Amgen, Bayer, Bristol Myers Squibb, Merck, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2021 American College of Cardiology Foundation",

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T1 - In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction

AU - Rao, Vishal N.

AU - Murray, Evan

AU - Butler, Javed

AU - Cooper, Lauren B.

AU - Cox, Zachary L.

AU - Fiuzat, Mona

AU - Green, Jennifer B.

AU - Lindenfeld, Jo Ann

AU - McGuire, Darren K.

AU - Nassif, Michael E.

AU - O'Brien, Cara

AU - Pagidipati, Neha

AU - Sharma, Kavita

AU - Vaduganathan, Muthiah

AU - Vardeny, Orly

AU - Fonarow, Gregg C.

AU - Mentz, Robert J.

AU - Greene, Stephen J.

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N2 - Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to the outpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications to the U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4 patients hospitalized for worsening heart failure die or are readmitted within 30 days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this population with the urgency it deserves.

AB - Sodium-glucose cotransporter-2 inhibitor therapy is well suited for initiation during the heart failure hospitalization, owing to clinical benefits that accrue rapidly within days to weeks, a strong safety and tolerability profile, minimal to no effects on blood pressure, and no excess risk of adverse kidney events. There is no evidence to suggest that deferring initiation to the outpatient setting accomplishes anything beneficial. Instead, there is compelling evidence that deferring in-hospital initiation exposes patients to excess risk of early postdischarge clinical worsening and death. Lessons from other heart failure with reduced ejection fraction therapies highlight that deferring initiation of guideline-recommended medications to the U.S. outpatient setting carries a >75% chance they will not be initiated within the next year. Recognizing that 1 in 4 patients hospitalized for worsening heart failure die or are readmitted within 30 days, clinicians should embrace the in-hospital period as an optimal time to initiate sodium-glucose cotransporter-2 inhibitor therapy and treat this population with the urgency it deserves.

KW - guideline-directed medical therapy

KW - heart failure

KW - in-hospital prescribing

KW - medical therapy

KW - sodium-glucose cotransporter-2 inhibitors

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SN - 0735-1097

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JO - Journal of the American College of Cardiology.

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ER -

In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction

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