Author + information
- Received February 1, 2019
- Revision received February 17, 2019
- Accepted February 18, 2019
- Published online May 13, 2019.
- Stephen J. Greene, MDa,b@SJGreene_md,
- Gregg C. Fonarow, MDc@gcfmd,
- Adam D. DeVore, MD, MHSa,b,
- Puza P. Sharma, MBBS, MPH, PhDd,
- Muthiah Vaduganathan, MD, MPHe,
- Nancy M. Albert, PhDf,
- Carol I. Duffy, DOd,
- C. Larry Hill, PhDa,
- Kevin McCague, MAd,
- J. Herbert Patterson, PharmDg,
- John A. Spertus, MD, MPHh,
- Laine Thomas, PhDa,
- Fredonia B. Williams, EdDi,
- Adrian F. Hernandez, MD, MHSa,b and
- Javed Butler, MD, MPH, MBAj,∗ (, )@JavedButler1@DCRINews@UMMCMedicine
- aDuke Clinical Research Institute, Durham, North Carolina
- bDivision of Cardiology, Duke University School of Medicine, Durham, North Carolina
- cAhmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, California
- dNovartis Pharmaceuticals Corporation, East Hanover, New Jersey
- eBrigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts
- fNursing Institute and Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
- gEshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina
- hSaint Luke's Mid America Heart Institute and the University of Missouri-Kansas City, Kansas City, Missouri
- iMended Hearts, Huntsville, Alabama
- jDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- ↵∗Address for correspondence:
Dr. Javed Butler, University of Mississippi Medical Center, Department of Medicine (L650), 2500 N. State Street, Jackson, Mississippi 39216.
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.
The CHAMP-HF registry is funded by Novartis Pharmaceuticals Corporation (East Hanover, New Jersey). Dr. Greene is supported by the National Heart, Lung, and Blood Institute (NHLBI) T32 postdoctoral training grant (T32HL069749-14), a Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; and has received research support from Amgen and Novartis. Dr. Fonarow has received research funding from the National Institutes of Health; and has been a consultant for Amgen, Abbott, Bayer, Janssen, Medtronic, and Novartis. Dr. DeVore has received research funding from Akros Medical, the American Heart Association, Amgen, Bayer, Intra-Cellular Therapies, Luitpold Pharmaceuticals, the NHLBI, Novartis, and PCORI; and has been a consultant for Novartis, Mardil Medical, and Procyrion. Dr. Sharma is an employee of Novartis. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541); and has served on advisory boards or received research funding from AstraZeneca, Bayer AG, and Baxter Healthcare. Dr. Albert has served as a consultant for Novartis and Boston Scientific. Dr. Duffy is an employee of and owns stock in Novartis. Mr. McCague is an employee of and owns stock in Novartis. Dr. Patterson has received research funding from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Otsuka, and Novartis; and has served as a consultant for Novartis. Dr. Spertus has served as a consultant for Novartis, Bayer, and Janssen; and owns the copyright to the Kansas City Cardiomyopathy Questionnaire. Dr. Hernandez has received consulting fees from AstraZeneca, Bayer, Boston Scientific, Merck, Novartis, and Sanofi; and has received research support from AstraZeneca, GlaxoSmithKline, Luitpold, Merck, and Novartis. Dr. Butler has received research support from the National Institutes of Health, PCORI, and the European Union; and has served as a consultant for Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, G3 Pharmaceutical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, and ZS Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received February 1, 2019.
- Revision received February 17, 2019.
- Accepted February 18, 2019.
- 2019 American College of Cardiology Foundation
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