Author + information
- Received March 28, 2019
- Revision received July 11, 2019
- Accepted July 15, 2019
- Published online October 9, 2019.
- Joost C. Beusekamp, BSca,
- Jasper Tromp, MD, PhDa,b,c,
- John G.F. Cleland, MD, PhDd,
- Michael M. Givertz, MDe,
- Marco Metra, MD, PhDf,
- Christopher M. O’Connor, MD, PhDg,
- John R. Teerlink, MD, PhDh,
- Piotr Ponikowski, MD, PhDi,
- Wouter Ouwerkerk, PhDb,j,
- Dirk J. van Veldhuisen, MD, PhDa,
- Adriaan A. Voors, MD, PhDa and
- Peter van der Meer, MD, PhDa,∗ ()
- aDepartment of Cardiology, University of Groningen, Groningen, the Netherlands
- bDepartment of Cardiology, National Heart Centre Singapore, Singapore
- cDuke-National University of Singapore Medical School, Singapore
- dDepartment of Cardiology, University of Hull, Hull, United Kingdom
- eDepartment of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- fCardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
- gDuke University Medical Center, Durham, North Carolina
- hUniversity of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California
- iDepartment of Cardiology, Medical University, Clinical Military Hospital, Wroclaw, Poland
- jDepartment of Dermatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands
- ↵∗Address for correspondence:
Prof. Peter van der Meer, Department of Cardiology, Thorax Center, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, Groningen 9700 RB, the Netherlands.
Objectives This study investigated associations between incident hyperkalemia during acute heart failure (HF) hospitalizations and changes in renin-angiotensin-aldosterone system (RAAS) inhibitors.
Background Hyperkalemia is a potential complication of RAAS inhibitors. For patients with HF, fear of hyperkalemia may lead to failure to deliver guideline-recommended doses of RAAS inhibitors.
Methods Serum potassium concentrations were measured daily from baseline (<24 h after admission) until discharge or day 7 in 1,589 patients enrolled in the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) trial. Incident hyperkalemia was defined as at least 1 episode of potassium >5.0 mEq/l. The primary outcome was all-cause mortality at 180 days.
Results Overall, serum potassium concentrations increased from 4.3 ± 0.6 mEq/l at baseline to 4.5 ± 0.6 mEq/l at discharge or day 7 (p < 0.001). Patients developing incident hyperkalemia (n = 564; 35%) were more often taking mineralocorticoid antagonists (MRAs) therapy prior to hospitalization and were more likely to have them down-titrated during hospitalization, independent of confounders. Incident hyperkalemia was not associated with adverse outcomes. Yet, down-titration of MRAs during hospitalization was independently associated with 180-day mortality (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.15 to 2.60), regardless of incident hyperkalemia (pinteraction > 0.1). Patients with incident hyperkalemia who were discharged with the same or increased dose of MRAs (HR: 0.52; 95% CI: 0.32 to 0.85) or angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) (HR: 0.47; 95% CI: 0.29 to 0.77) had a lower 180-day mortality.
Conclusions Incident hyperkalemia is common in patients hospitalized for acute HF and is not associated with adverse outcomes. Incident hyperkalemia is associated with down-titration of MRAs, but patients who maintained or increased their dose of MRAs and/or ACE inhibitors/ARB during acute HF hospitalization had better 180-day survival.
Dr. Cleland is an advisory board member and has received honoraria for lectures from Vifor. Dr. Metra consults for Bayer, Novartis, and Servier; and has received speakers’ fees from Abbott Vascular. Dr. O'Connor consults for Bristol-Myers Squibb, Merck, Windtree, and Bayer; and has received research support from Roche Diagnostics. Dr. Teerlink has received research support from Abbott, Amgen, Bayer, Cytokinetics, Medtronic, Novartis, and St. Jude; and is a consultant for Amgen, Bayer, Cytokinetics, Medtronic, Merck, Novartis, and St. Jude. Dr. van Veldhuisen has received travel support from Novartis and Corvia Medical. Dr. Voors is a consultant for Amgen, Boehringer Ingelheim, AstraZeneca, Bayer, Cytokinetics, Myokardia, Novartis, and Vifor Pharma; and has received research support from and consults for Roche. Dr. Van der Meer is a consultant for Vifor Pharma, Servier, Novartis, and Pfizer; and has received research grants from Vifor Pharma, Astra Zeneca, Ionis, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 28, 2019.
- Revision received July 11, 2019.
- Accepted July 15, 2019.
- 2019 American College of Cardiology Foundation
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