Author + information
- Received November 20, 2018
- Accepted November 26, 2018
- Published online February 25, 2019.
- Javed Butler, MD, MPH, MBAa,∗ (, )@JavedButler1,
- Mei Yang, PhDb,
- Massimiliano Alfonzo Manzi, MBAc,
- Gregory P. Hess, MD, MBA, MScc,d,
- Mahesh J. Patel, MDb,
- Thomas Rhodes, PhDb and
- Michael M. Givertz, MDe
- aDepartment of Medicine, University of Mississippi, Jackson, Mississippi
- bMerck & Co., Inc., Kenilworth, New Jersey
- cScientific Studies, Symphony Health, Conshohocken, Pennsylvania
- dLeonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania
- eCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Javed Butler, Department of Medicine (L650), University of Mississippi, 2500 North State Street, Jackson, Mississippi 39216.
Background Epidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described.
Objectives The purpose of this study was to describe incidence, clinical characteristics, treatment, and outcomes of patients with HFrEF who develop worsening heart failure (HF) in the real-world setting.
Methods Data on patients with incident HFrEF from the National Cardiovascular Data Registry PINNACLE were linked to pharmacy, private practitioner, and hospital claims databases. Incidence, clinical characteristics, treatment (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist) and outcomes of patients with worsening HF, defined as ≥90 days of stable HF with subsequent worsening requiring intravenous diuretic agents, were assessed.
Results Of 11,064 HFrEF patients, 1,851 (17%) developed worsening HF on average 1.5 years following initial HF diagnosis. Patients who developed worsening HF were more likely to be African American, be octogenarians, and have higher comorbidity burden (p < 0.001). At the onset of worsening HF, 42.4% of patients were on monotherapy, 43.4% were on dual therapy, and 14.1% were on triple therapy. A total of 48%, 61%, and 98% of patients were on >50% target dose for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, and mineralocorticoid receptor antagonist, respectively. The 2-year mortality rate was 22.5%, and 56% of patients were rehospitalized within 30 days of the worsening HF event.
Conclusions In the real-world setting, 1 in 6 patients with HFrEF develop worsening HF within 18 months of HF diagnosis. These patients have a high risk for 2-year mortality and recurrent HF hospitalizations. The use of standard-of-care therapies both before and after the onset of worsening HF is low. With high unmet medical need, patients with worsening HF require novel treatment strategies as well as greater optimization of existing guideline-directed therapy.
Support for this study, including support for medical writing, was provided by Merck & Co., Inc., Kenilworth, New Jersey. Dr. Butler has received research support from the National Institutes of Health (NIH), Patient-Centered Outcomes Research Institute, and the European Union; and has served as a consultant for Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squib, CVRx, G3 Pharmaceutical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, and ZS Pharma. Dr. Yang is an employee and shareholder of Merck & Co., the study sponsor. Mr. Manzi and Dr. Hess are prior employees of Symphony Health, which received research support from Merck & Co. for the design and conduct of this study. Dr. Hess has conducted funded studies with governmental agencies, e.g., the NIH, and professional societies, e.g., the American College of Cardiology; has served on the advisory boards of Heron Therapeutics and US Worldmeds; has served on the clinical excellence committee of Millennium Health; and has received honoraria from Millennium Health, Heron Therapeutics, and US Worldmeds. Drs. Yang and Patel are employees and shareholders of Merck & Co., the study sponsor. Dr. Rhodes is a prior employee and shareholder of Merck & Co., Inc., the study sponsor. Michael Givertz has served as a consultant to and scientific advisor for Merck & Co.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received November 20, 2018.
- Accepted November 26, 2018.
- 2019 American College of Cardiology Foundation
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