Author + information
- Received April 26, 2019
- Revision received May 28, 2019
- Accepted May 29, 2019
- Published online September 11, 2019.
- Yevgeniy Khariton, MDa,∗ (, )
- Gregg C. Fonarow, MDb,
- Suzanne V. Arnold, MD, MHAa,
- Ann Hellkamp, MSc,
- Michael E. Nassif, MD, MSd,
- Puza P. Sharma, MBBSe,
- Javed Butler, MD, MPH, MBAf,
- Laine Thomas, PhDc,
- Carol I. Duffy, DOe,
- Adam D. DeVore, MD, MHSg,
- Nancy M. Albert, PhDh,
- J. Herbert Patterson, PharmDi,
- Fredonia B. Williams, EdDj,
- Kevin McCague, MAe and
- John A. Spertus, MD, MPHa
- aDepartments of Cardiology and Cardiovascular Outcomes Research, Saint Luke’s Mid America Heart Institute/University of Missouri-Kansas City, Kansas City, Missouri
- bDepartment of Cardiology, Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, California
- cDuke Clinical Research Institute, Durham, North Carolina
- dDepartment of Cardiology, Washington University School of Medicine in Saint Louis, Saint Louis, Missouri
- eNovartis Pharmaceuticals Corp, East Hanover, New Jersey
- fDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- gDivision of Cardiology, Department of Medicine, and the Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- hCleveland Clinic, Cleveland, Ohio
- iEshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina
- jMended Hearts, Huntsville, Alabama
- ↵∗Address for correspondence:
Dr. Yevgeniy Khariton, Saint Luke’s Mid America Heart Institute, 4401 Wornall Road, Kansas City, Missouri 64111.
Objectives This study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).
Background Although therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients’ health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients’ symptoms, functions, and quality of life is unknown.
Methods Health status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.
Results Multivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p < 0.001) over a median (interquartile range [IQR]) of 57 (32, 104) days. The proportions of ARNI versus no-ARNI groups with ≥10-point (large) and ≥20-point (very large) improvements in KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12, respectively.
Conclusions In routine clinical care, ARNI therapy was associated with early improvements in health status, with 20% experiencing a very large health status benefit compared with 12% who were not started on ARNI therapy. These findings support the use of ARNI to improve patients’ symptoms, functions, and quality of life.
The CHAMP-HF (Change the Management of Patients with Heart Failure) and the present study were funded by the Novartis Pharmaceuticals Corp. Drs. Khariton and Nassif are supported by U.S. National Heart, Lung, and Blood Institutes award T32HL110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. National Institutes of Health (NIH). Dr. Khariton had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr. Sharma was an employee of Novartis at the time of the development and review of this paper. Dr. Spertus has received research support from National Institute of Health (NIH), American College of Cardiology Foundation, Bayer, Novartis, and Abbott Vascular; and he serves on a Scientific Advisory Board for United Healthcare; and is a consultant for Novartis, V-Wave, AstraZeneca, Janssen, Corvia, and Bayer; and holds patent rights to the Kansas City Cardiomyopathy Questionnaire; and he holds equity in Health Outcomes Sciences. Dr. Thomas has received research support from Novartis Pharmaceuticals Corp. Dr. Fonarow has received research support from NIH; and is a consultant for Abbott, Amgen, Bayer, Janssen, Medtronic, and Novartis. Dr. DeVore has received research support from the American Heart Association, Amgen, NIH, and Novartis; and is a consultant for Novartis. Dr. Butler has received research support from NIH and European Union; and is a consultant for Amgen, Bayer, Boehringer Ingelheim, Cardiocell, CVRx, Gilead, Janssen, Medtronic, Merck, Novartis, Relypsa, and ZS Pharma. Dr. Albert is a consultant for Novartis, AstraZeneca, and Boston Scientific; and has received honoraria from Novartis. Dr. J. Herbert Patterson reports consulting and research support for Novartis. Drs. Duffy and McCague are employees of Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 26, 2019.
- Revision received May 28, 2019.
- Accepted May 29, 2019.
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