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Kidney Week

Abstract: FR-PO405

Effects of Spironolactone (SPL) on Arrhythmias in Hemodialysis Patients: Secondary Results of the SPin-D Trial

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Charytan, David M., New York University School of Medicine, New York, New York, United States
  • Hsu, Jesse Yenchih, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Himmelfarb, Jonathan, Kidney Research Institute, Seattle, Washington, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States
  • Landis, J. Richard, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Mehrotra, Rajnish, Kidney Research Institute, Seattle, Washington, United States
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Kliger, Alan S., Yale New Haven Health System, New Haven, Connecticut, United States
  • McCausland, Finnian R., Harvard Medical School, Boston, Massachusetts, United States
  • Dember, Laura M., University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States

Group or Team Name

  • Hemodialysis Novel Therapies Consortium
Background

Aldosterone may contribute to the development of arrhythmias in HD patients. Whether treatment with SPL affects the risk of arrhythmias in this setting is unknown.

Methods

The Spironolactone in Dialysis (SPin-D) trial evaluated the safety of SPL for 36 weeks at 12.5 mg, 25 mg, or 50 mg vs placebo in maintenance HD patients. We analyzed data from a subset of participants with arrhythmia monitoring for 7 days at baseline (N=35), 6-weeks (N=37), and end of study (N=53). Adjusted Poisson models including treatment, time point and randomization stratification factors were used to analyze associations of SPL, SPL dose, and serum potassium (K) with the incidence rates of arrhythmias during follow-up.

Results

Conduction blocks or bradycardia and atrial fibrillation or flutter (AF) were common while ventricular arrhythmia was infrequent (Table). Conduction defects or bradycardia were more frequent with SPL compared with placebo in unadjusted and adjusted models. Reduction in AF risk with SPL vs. placebo was less robust at higher SPL dose: (adjusted rate ratios [RR], 95% CI) SPL 12.5 mg (0.09, 0.01-0.77), 25 mg (0.40, 0.06-2.72) and 50 mg/daily (0.89, 0.21-0.80), and conduction block or bradycardia was more frequent at higher SPL dose: (adjusted RR, 95% CI) SPL 12.5 mg (1.56, 0.93-2.52), 25 mg (1.45, 1.06-1.97) and 50 mg (3.00, 1.73-5.20). The RR per 1 mEq/L increase in serum K was 1.54, 95% CI: 0.89-2.65 for AF and 1.20, 0.78-1.86 for bradycardia/block.

Conclusion

Arrhythmias occur with a high incidence in maintenance HD patients with AF and bradycardias/conduction blocks occurring more frequently than ventricular arrhythmias. SPL may reduce AF but increase conduction blocks and bradycardia. Additional studies are needed to confirm these findings, evaluate the effects of SPL dose, and determine if increased K mediates SPL-associated arrythmias.

Arrhythmia Rate at Baseline and Follow-Up
 Overall Rate at BaselinePlaceboSPL 12.5 mgSPL 25 mgSPL 50 mgCombined SPL During Follow-Up
Arrhythmia Type      
Atrial Fibrillation or Flutter5.613.21.25.311.76.3
Conduction Block or Bradycardia3.415.524.422.346.533.6
Ventricular Tachycardia or Fibrillation0.40.80.00.00.70.2
Sinus Bradycardia or Asystole0.71.41.40.015.46.1
Sinus Tachycardia, Supraventricular Tachycardia, or Wide Complex Tachycardia14.913.712.510.915.313.0

Rates are provided as events per 100 patient-days and are show for combined placebo and spironolactone group at baseline and by randomized treatment group during follow-up.

Funding

  • NIDDK Support