Effects of Spironolactone on Arrhythmias in Hemodialysis Patients: Secondary Results of the SPin-D Randomized Controlled Trial

Finnian R. Mc Causland, Renal Division, Department of Medicine, Brigham and Women's Hospital.
Jesse Y. Hsu, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jonathan Himmelfarb, Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Talat Alp Ikizler, Division of Nephrology and Hypertension, Department of Medicine, and Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Dominic S. Raj, Division of Renal Diseases and Hypertension, George Washington University School of Medicine, Washington, District of Columbia, USA.
Rajnish Mehrotra, Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA.
Sushrut S. Waikar, Section of Nephrology, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.
Paul L. Kimmel, National Institute of Diabetes Digestive and Kidney Diseases, Bethesda, Maryland, USA.
Alan S. Kliger, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
Laura M. Dember, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David M. Charytan, Nephrology Division, Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA.

Document Type

Journal Article

Publication Date

2-10-2023

Journal

Kidney360

DOI

10.34067/KID.0000000000000067

Abstract

Background Patients receiving maintenance hemodialysis (HD) have a high incidence of cardiovascular events, including arrhythmia and sudden death. Spironolactone reduces the risk of cardiovascular events and sudden death in patients with heart failure, but the effects of spironolactone on arrhythmic events in patients treated with maintenance HD are unclear. Methods The Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD (SPin-D) trial, was a 36-week randomized, placebo-controlled, double-blind trial comparing 3 different doses of spironolactone with placebo in maintenance HD patients. We performed a post-hoc analysis in a subset (n=57) who underwent extended electrocardiographic monitoring using a wearable device at baseline and follow-up. Generalized estimating equations models were fit to determine the associations of spironolactone (individual doses and combined) versus placebo on the incidence rate of predefined categories of arrhythmic events. Results The average age of participants was 55 ±12 years; 61% were male; and 77% were Black. The overall proportion of patients with at least one arrhythmia event was 43% (15/35) at baseline and 81% (43/53) at the end of follow-up. At the end of follow-up, the rate of bradycardic events or conduction blocks was higher in the combined spironolactone group, compared with placebo, (82.4 versus 38.7 events/100 patient days; P<0.001). Similar findings were noted in adjusted models, but did not meet statistical significance (adjusted rate ratio of 2.04; 95%CI 0.83 - 5.05). Conclusions In a 36-week trial of patients receiving maintenance hemodialysis, a higher frequency of bradycardia and conduction blocks was observed among those treated with spironolactone treatment compared with placebo. Larger studies are required to investigate the longer-term effects of spironolactone on cardiac conduction in patients receiving hemodialysis.

Department

Medicine

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