Digoxin use among patients who are on hemodialysis (HD) may increase their risk of death, especially if they have low predialysis potassium levels, a study showed.

HD patients who used digoxin had a 28% increased risk of death compared with those who did not use the drug, after adjusting for potential confounders, Kevin E. Chan, MD, of Fresenius Medical Care in Waltham, Mass., and colleagues reported in the Journal of the American Society of Nephrology (2010;21:1550-1559). In addition, mortality risk increased by 19% for each 1 ng/mL increment in serum digoxin level. Compared with predialysis serum potassium levels above 4.6 mEq/L, levels below 4.3 mEq/L are associated with a 2.53 times increased risk of death.

The study involved analyses of data from 120,864 incident HD patients, 4,549 of whom were digoxin users.

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“Overall, we suggest caution for digoxin use in the general HD population, given its prescription was associated with increased mortality in this study,” the authors wrote.

Few studies have been conducted to verify that digoxin is safe in HD patients. Shifts in potassium levels during dialysis may play an important role in the therapeutic effects and toxicity of the drug. The biological mechanism of action of digoxin involves its binding to ATPase, and potassium competes for the same binding site. Consequently, hyperkalemia may decrease the effectiveness of digoxin, whereas hypokalemia can potentiate toxicity, the authors explained.