Author + information
- Received April 7, 2019
- Revision received May 23, 2019
- Accepted May 28, 2019
- Published online July 29, 2019.
- Awais Malik, MDa,b,
- Ravi Masson, MDa,b,
- Steven Singh, MDa,b,
- Wen-Chih Wu, MDc,d,
- Milton Packer, MDe,
- Bertram Pitt, MDf,
- Finn Waagstein, MD, PhDg,
- Charity J. Morgan, PhDa,h,
- Richard M. Allman, MDh,i,
- Gregg C. Fonarow, MDj and
- Ali Ahmed, MD, MPHa,b,i,∗ (, )@DCVAMC@gcfmd
- aVeterans Affairs Medical Center, Washington, DC
- bGeorgetown University, Washington, DC
- cVeterans Affairs Medical Center, Providence, Rhode Island
- dBrown University, Providence, Rhode Island
- eBaylor University Medical Center, Dallas, Texas
- fUniversity of Michigan, Ann Arbor, Michigan
- gUniversity of Gothenburg, Gothenburg, Sweden
- hUniversity of Alabama at Birmingham, Birmingham, Alabama
- iGeorge Washington University, Washington, DC
- jUniversity of California, Los Angeles, Los Angeles, California
- ↵∗Address for correspondence:
Dr. Ali Ahmed, Washington DC VA Medical Center, 50 Irving Street NW, Washington, DC 20422.
Background The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented.
Objectives The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists.
Methods Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled.
Results Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778).
Conclusions Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs. Dr. Ahmed was supported in part by the National Institutes of Health through grants R01-HL085561, R01-HL085561-S, and R01-HL097047 from the National Heart, Lung, and Blood Institute. The OPTIMIZE-HF registry was sponsored by GlaxoSmithKline, but played no role in the design, conduct, analyses, or interpretation of the current study. Dr. Packer has served as a consultant for Abbvie, Akcea, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Cardiorentis, Daiichi-Sankyo, Gilead, NovoNordisk, Pfizer, Relypsa, Sanofi, and Theravance. Dr. Pitt has been a consultant to Bayer, Sanofi, AstraZeneca, KBP Pharmaceuticals, scPharmaceuticals, Sarfez, Relypsa/Vifor, and Cereno Scientific; has stock options in KBP Pharmaceuticals, Relypsda, and Sarfez; and holds U.S. patent # 9931412 for site-specific delivery of eplerenone to the myocardium. Dr. Fonarow has been a consultant to Abbott, Amgen, Bayer, Janssen, Medtronic, and Novartis; has received research funding from Novartis; and was the principal investigator of the OPTIMIZE-HF registry. 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 April 7, 2019.
- Revision received May 23, 2019.
- Accepted May 28, 2019.
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