Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week

Affiliations

¹ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA. Electronic address: mona.fiuzat@duke.edu.
² Division of Cardiology, Mount Sinai University Hospital, New York, New York, USA. Electronic address: https://twitter.com/CarineHamo.
³ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. Electronic address: https://twitter.com/JavedButler1.
⁴ Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.
⁵ Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA.
⁶ Division of Cardiology, University of California-Los Angeles, Los Angeles, California, USA. Electronic address: https://twitter.com/coconnormd.
⁷ Cardiology Division, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁸ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
⁹ Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
¹⁰ Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹¹ Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, California, USA.
¹² Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: https://twitter.com/mvaduganathan.
¹³ Center for Care Delivery and Outcomes Research, VA Health Care System, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
¹⁴ British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, United Kingdom.
¹⁵ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA; Inova Heart and Vascular Institute, Falls Church, Virginia, USA.

PMID: 35115106
PMCID: PMC9180686
DOI: 10.1016/j.jacc.2021.11.033

Review

Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week

Mona Fiuzat et al. J Am Coll Cardiol. 2022.

. 2022 Feb 8;79(5):504-510.

doi: 10.1016/j.jacc.2021.11.033.

Authors

Affiliations

¹ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA. Electronic address: mona.fiuzat@duke.edu.
² Division of Cardiology, Mount Sinai University Hospital, New York, New York, USA. Electronic address: https://twitter.com/CarineHamo.
³ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA. Electronic address: https://twitter.com/JavedButler1.
⁴ Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA.
⁵ Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA.
⁶ Division of Cardiology, University of California-Los Angeles, Los Angeles, California, USA. Electronic address: https://twitter.com/coconnormd.
⁷ Cardiology Division, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁸ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA.
⁹ Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
¹⁰ Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹¹ Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, California, USA.
¹² Cardiology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: https://twitter.com/mvaduganathan.
¹³ Center for Care Delivery and Outcomes Research, VA Health Care System, Minneapolis, Minnesota; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
¹⁴ British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, United Kingdom.
¹⁵ Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA; Inova Heart and Vascular Institute, Falls Church, Virginia, USA.

PMID: 35115106
PMCID: PMC9180686
DOI: 10.1016/j.jacc.2021.11.033

Abstract

With the current landscape of approved therapies for heart failure (HF), there is a need to determine the role of a standard background therapy against which novel therapies are studied. The Heart Failure Collaboratory convened a multistakeholder group of clinical investigators, clinicians, patients, government representatives including U.S. Food and Drug Administration and National Institutes of Health participants, payers, and industry in March 2021 to discuss whether standardization of background drug therapy is necessary in clinical trials in patients with HF. The current paper summarizes the discussion and provides potential conceptual approaches, with a focus on therapies indicated for HF with reduced ejection fraction.

Keywords: FDA; HFrEF; clinical trials; device therapy; drug therapy; guideline directed medical therapy; heart failure; medical therapy; medication.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Hamo has received support from the National Heart, Lung, and Blood Institute, National Institutes of Health (grant number T32 HL007024). Dr Butler has served as a consultant to Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Berlin Cures, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sequanna, and Vifor. Dr Fonarow has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis. 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, Relypsa, and Roche Diagnostics; has speaker engagements with Novartis and Roche Diagnostics; and has participated on clinical endpoint committees for studies sponsored by Galmed and Novartis. Dr Solomon has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cytokinetics, Edwards, Eisai, Ionis, Ironwood, Merck, MyoKardia, Novartis, Prothena, Pfizer, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr Lindenfeld has served as a consultant for AstraZeneca, Abbott, Allegiant, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave; and has received grants from AstraZeneca, Volumetrix, and Sensible Medical. Dr Abraham has received consulting fees from Abbott, ARCA biopharma, Boehringer Ingelheim, Cardionomic, CVRx, Edwards Lifesciences, Respicardia, Sensible Medical, and Vectorious; and has received salary support from V-Wave Medical. Dr Teerlink has received research grants and/or consulting fees from Abbott, AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, EBR Systems, Medtronic, Merck, and Novartis. Dr McMurray has had payments to his employer, Glasgow University, for his work on clinical trials, consulting and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; and has received personal payments from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Ionis, Lupin, ProAdWise Communications, Sun Pharmaceuticals, and Servier. Dr O’Connor has received grant or research support from Roche Diagnostics and Merck; and has received consulting fees from Merck, Bayer, Bristol Myers Squibb, Windtree, and Arena. All other authors have reported that they have no relationships related to the contents of this paper to disclose.

Figures

**FIGURE 1. Specific Versus Pragmatic Approaches to Background Heart Failure Drug Therapy**
A more pragmatic approach would include minimal requirements of background medical therapy, whereas a more precise approach involves treatment with all classes of goal directed therapy and target doses. *In absence of contraindications or documented intolerance. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI, = angiotensin receptor neprilysin inhibitor; BB = beta-blocker; MRA = mineralocorticoid receptor antagonist; SGLT2i = sodium-glucose transporter-2 inhibitor

**CENTRAL ILLUSTRATION. Potential Approaches to Background Drug Therapy for Heart Failure Patients**
**(Left)** 4 drug class approach; **(right)** GDMT score example. *Majority of patients on SGLT2i. †Drugs shown to improve outcomes in specific patient cohort. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor neprilysin inhibitor; MRA = mineralocorticoid receptor antagonist; RAAS = renin angiotensin aldosterone system; SGLT2i = sodium-glucose transporter-2 inhibitor.

See this image and copyright information in PMC

References

1. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2021;42(36):3599–3726. 10.1093/eurheartj/ehab368 - DOI - PubMed
1. Maddox TM, Januzzi JL, Allen LA, et al. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction. J Am Coll Cardiol 2021;77:772–810. - PubMed
1. Fiuzat M, Ezekowitz J, Alemayehu W, et al. Assessment of limitations to optimization of guideline-directed medical therapy in heart failure from the GUIDE-IT trial: a secondary analysis of a randomized clinical trial. JAMA Cardiology 2020;5:757–764. - PMC - PubMed
1. Greene SJ, Butler J, Albert NM, et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. J Am Coll Cardiol 2018;72:351–366. - PubMed
1. O’Connor CM. COAPTing heart failure physicians, interventional cardiologists, and cardiothoracic surgeons. J Am Coll Cardiol HF 2018;6:967–968. - PubMed

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Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week

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Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week

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