Titration of medical therapy for heart failure with reduced ejection fraction
Open accessAbstract
Background Guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) have medical therapy titrated to target doses derived from clinical trials, as tolerated. The degree to which titration occurs in contemporary U.S. practice is unknown.Objectives This study sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and to identify associated factors and reasons for medication changes.Methods Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry with complete medication data and no contraindications to medical therapy, use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) were examined at baseline and at 12-month follow-up.Results At baseline, 658 (25%), 525 (20%), 287 (11%), and 45 (2%) patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI therapy, respectively. At 12 months, proportions of patients with medication initiation or dose increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation or dose decrease were 4%, 7%, 11%, and 3%, respectively. Over 12 months, <1% of patients were simultaneously treated with target doses of ACEI/ARB/ARNI, beta-blocker, and MRA. In multivariate analysis, across the classes of medications, multiple patient characteristics were associated with a higher likelihood of initiation or dose increase (e.g., previous HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation or dose decrease (e.g., previous HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common reasons for discontinuations and dose decreases of each therapy, but the relative contributions from patient preference, health team, and systems-based reasons varied by medication.Conclusions In this contemporary U.S. registry, most eligible HFrEF patients did not receive target doses of medical therapy at any point during follow-up, and few patients had doses increased over time. Although most patients had no alterations in medical therapy, multiple clinical factors were independently associated with medication changes. Further quality improvement efforts are urgently needed to improve guideline-directed medication titration for HFrEF.
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Registry data continue to identify suboptimal initiation and titration of goal-directed medical therapy in patients with ambulatory heart failure.
“Registry data continue to identify suboptimal initiation and titration of goal-directed medical therapy in patients with ambulatory HF.”
From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [4]
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Cardiovascular Statistics in the United States, 2026
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2026 ESC Guidelines for the management of heart failure
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Self-citationImplementing Guideline-Directed Medical Therapy for Heart Failure
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A Novel Approach to Medical Management of Heart Failure With Reduced Ejection Fraction
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Bridging Treatment Implementation Gaps in Patients With Heart Failure
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Self-citationClinical Inertia Among Outpatients With Heart Failure
Swat, S. A., Helmkamp, L. J., Tietbohl, C. K., Thompson, J. S., Fitzgerald, M., McIlvennan, C. K., Harger, G., Ho, P. M., Ahmad, F. S., Ahmad, T., et al. (2023) · JACC Heart Failure · doi:10.1016/j.jchf.2023.06.022 · Cited by 52 · see citing works
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Self-citationContemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF
Peikert, A., Bart, B. A., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Kosiborod, M., Desai, A. S., Jhund, P. S., Lam, C. S. P., Inzucchi, S. E., et al. (2023) · JACC Heart Failure · doi:10.1016/j.jchf.2023.09.007 · Cited by 50 · see citing works
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Self-citationReasons for Lack of Improvement in Treatment With Evidence-Based Therapies in Heart Failure
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JCS/JHFS 2025 Guideline on Diagnosis and Treatment of Heart Failure
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Predicting High-Risk Patients and High-Risk Outcomes in Heart Failure
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The Evolving Concept of Secondary Mitral Regurgitation Phenotypes
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Patient Perceptions and Familiarity With Medical Therapy for Heart Failure
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Self-citationThe Role of Nurse Practitioners in the Management of Heart Failure Patients and Programs
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Self-citationComparative Effectiveness of Dosing of Medical Therapy for Heart Failure: From the CHAMP-HF Registry
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Prescribing of Statins After Lower Extremity Revascularization Procedures in the US
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Quadruple Medical Therapy for Heart Failure
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Self-citationTreatment of HF in an Era of Multiple Therapies
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Self-citationHeart Failure Management through Telehealth: Expanding Care and Connecting Hearts
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Heart failure treatment up‐titration and outcome and age: an analysis of BIOSTAT‐CHF
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Underutilization of Guideline-Directed Medical Therapy in Heart Failure
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- Authors
- Greene, S. J., Fonarow, G. C., DeVore, A. D., Sharma, P. P., Vaduganathan, M., Albert, N. M., Duffy, C. I., Hill, C. L., McCague, K., Patterson, J. H., Spertus, J. A., Thomas, L., Williams, F. B., Hernandez, A. F., & Butler, J.
- Affiliations
- Duke University (US)
- University of California, Los Angeles (US)
- Novartis (United States) (US)
- Brigham and Women's Hospital (US)
- Cleveland Clinic (US)
- University of North Carolina at Chapel Hill (US)
- University of Missouri–Kansas City (US)
- University of Mississippi Medical Center (US)
- Corresponding author
- Butler, Javed
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 73
- Issue
- 19
- Pages
- 2365-2383
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC7197490
- OpenAlex
- W2919920736
- Cited by
- 500
- References
- 25
- Citations by year
- 2026: 45 · 2025: 51 · 2024: 71 · 2023: 93 · 2022: 72 · 2021: 74 · 2020: 66 · 2019: 26 · 2013: 1
- FWCI
- 42.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (UL1TR002541, 5t32hl069749-20)
- National Heart, Lung, and Blood Institute (T32-HL069749)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- heart failure with reduced ejection fraction, guideline-directed medical therapy, ACE inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, drug discontinuation, dose changes, quality of life, functional class, prior hospitalization
- MeSH terms
- Aged, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Heart Failure, Humans, Male, Middle Aged, Prospective Studies, Quality of Life, Stroke Volume, Ventricular Dysfunction, Left
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