Author + information
- Received February 1, 2019
- Revision received February 17, 2019
- Accepted February 18, 2019
- Published online March 4, 2019.
- Stephen J. Greene, MDa,b,
- Gregg C. Fonarow, MDc,
- 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,∗ (, )@SJGreene_md
- aDuke Clinical Research Institute, Durham, NC
- bDivision of Cardiology, Duke University School of Medicine, Durham, NC
- cAhmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, CA
- dNovartis Pharmaceuticals Corporation, East Hanover, NJ
- eBrigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA
- fNursing Institute and Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, OH
- gEshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC
- hSaint Luke's Mid America Heart Institute and the University of Missouri-Kansas City, Kansas City, MO
- iMended Hearts, Huntsville, AL
- jDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS
- ↵∗Address for Correspondence: Javed Butler, MD, MPH, MBA University of Mississippi Medical Center Department of Medicine (L650) 2500 N. State Street Jackson, Mississippi 39216. Telephone: 601-984-5600 Fax: 601-984-5608.
Background Guidelines recommend titration of medical therapy for heart failure with reduced ejection fraction (HFrEF) to target doses derived from clinical trials. The degree to which titration occurs in contemporary United States (U.S.) practice is unknown.
Objectives We sought to characterize longitudinal titration of HFrEF medical therapy in clinical practice and identify associated factors and reasons for medication changes.
Methods Among 2,588 U.S. outpatients with chronic HFrEF in the CHAMP-HF 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 12-month follow-up.
Results At baseline, 658, 525, 287, and 45 patients were receiving target doses of MRA, beta-blocker, ACEI/ARB, and ARNI, respectively. At 12-months, proportions of patients with medication initiation/dosing increase were 6% for MRA, 10% for beta-blocker, 7% for ACEI/ARB, and 10% for ARNI; corresponding proportions with discontinuation/dosing decrease were 4%, 7%, 11%, and 3%. 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 medication, multiple patient characteristics were associated with higher likelihood of initiation/dosing increase (e.g., prior HF hospitalization, higher blood pressure, lower ejection fraction) and discontinuation/dosing decrease (e.g., prior HF hospitalization, impaired quality of life, more severe functional class). Medical reasons were the most common underlying reasons for discontinuations and dosing decreases, but patient preference, health team, and systems-based reasons varied by medication.
Conclusions In this contemporary U.S. registry, the large majority of 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.
FUNDING: The CHAMP-HF registry is funded by Novartis Pharmaceuticals Corporation (East Hanover, New Jersey).
DISCLOSURES: Dr. Greene is supported by the National Heart Lung and Blood Institute 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 reports research funding from the NIH and serving as a consultant for Amgen, Bayer, Medtronic, and Novartis. Dr. DeVore reports receiving research funding from Akros Medical, the American Heart Association, Amgen, Bayer, Intra-Cellular Therapies, Luitpold Pharmaceuticals, the NHLBI, Novartis, and PCORI and serving as a consultant for Novartis. Drs. Sharma and Duffy and Mr. McCague report being 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 reports serving as a consultant for Novartis and Boston Scientific. Dr. Patterson reports research funding from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Otsuka and Novartis and serves as a consultant to Novartis. Dr. Spertus reports that, relevant to this work, he serves as a consultant for Novartis and owns the copyright to the Kansas City Cardiomyopathy Questionnaire. Dr. Hernandez reports consulting fees from AstraZeneca, Bayer, Boston Scientific, Merck, Novartis, Sanofi, and research support from AstraZeneca, GlaxoSmithKline, Luitpold, Merck, Novartis. Dr. Butler has received research support from the National Institutes of Health, PCORI and the European Union; and serves as a consultant for Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmacautical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, and ZS Pharma. All other authors report no disclosures.
- Received February 1, 2019.
- Revision received February 17, 2019.
- Accepted February 18, 2019.
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