Digoxin Use Linked to Mortality in End-Stage Renal Disease

Digoxin is frequently prescribed for the management of congestive heart failure and atrial fibrillation, as it works as both a positive inotrope and a negative chronotrope. It accomplishes these actions through increasing intracellular levels of sodium and calcium in the cardiac myocyte via inhibition of the Na+/K+-ATPase pump.

Both digoxin and potassium compete for this same myocyte-binding site, meaning that hypokalemia can potentiate digoxin toxicity (whereas hyperkalemia can decrease the effectiveness of digoxin). This relationship between potassium and the action of digoxin could be particularly problematic for patients receiving dialysis, for whom potassium levels fluctuate significantly at approximately the time of dialysis. The current study examines patient outcomes among individuals receiving digoxin during hemodialysis.
Digoxin use is linked to mortality in patients with end-stage renal disease, according to the results of a retrospective cohort study reported online June 24 in the Journal of the American Society of Nephrology.
"We were surprised to find that digoxin use increased death risk in dialysis patients, especially in patients on higher doses," said lead author Kevin E. Chan, MD, MSci, from Fresenius Medical Care North America in Waltham, Massachusetts, in a news release. "Although digoxin has been prescribed by doctors for over 200 years, widespread monitoring studies have not been conducted to examine the penetration, effectiveness, and safety of the drug among patients on dialysis."
Digoxin use was associated with a 28% increased mortality risk (hazard ratio

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1.28; 95% confidence interval [CI], 1.25 - 1.31). Increase in serum digoxin level was also a significant predictor of death, with an HR of 1.19 per ng/mL increase (95% CI, 1.05 - 1.35). Patients with lower predialysis serum potassium levels had the strongest association of increased mortality with digoxin level (HR, 2.53 [P = .01] for potassium level < 4.3 mEq/L vs HR, 0.86 [P = .35] for potassium level > 4.6 mEq/L).
"[D]igoxin use among patients who are on hemodialysis associates with increased mortality, especially among those with low predialysis K [potassium]," the study authors write.
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