Digoxin Associates with Mortality in ESRD

Abstract

The safety of prescribing digoxin in ESRD is unknown. Hypokalemia, which frequently occurs among dialysis patients, may enhance the toxicity of digoxin. Here, we analyzed the association between digoxin prescription and survival in a retrospective cohort using covariate-and propensity score-adjusted Cox models to minimize the potential for confounding by indication. Among 120,864 incident hemodialysis patients, digoxin use associated with a 28% increased risk for death (hazard ratio [HR] 1.28; 95% confidence interval 1.25 to 1.31). Increasing serum digoxin level was also significantly associated with mortality (HR 1.19 per ng/ml increase; 95% confidence interval 1.05 to 1.35). This increased mortality risk with level was most pronounced in patients with lower predialysis serum potassium (K) levels (HR 2.53 [P ϭ 0.01] for K Ͻ4.3 mEq/L versus HR 0.86 [P ϭ 0.35] for K Ͼ4.6 mEq/L). In conclusion, digoxin use among patients who are on hemodialysis associates with increased mortality, especially among those with low predialysis K concentrations.

Digitalis Toxicity: A Fading but Crucial Complication to Recognize

“…Increasing serum digoxin concentrations were significantly associated with mortality, especially in patients with predialysis serum potassium levels of Ͻ4.3 mEq/L. 31 The development of digoxin antibody Fab fragments has been shown to be highly effective in treating life-threatening signs of digoxin toxicity, 30,32 After administration, serum digoxin concentration levels cannot be used for accurate assessment due to the rapid extraction of digoxin from tissues into plasma. The resultant high concentrations detected are from the Fab-digoxin complex.…”

Digitalis and Hemodialysis Is a Bad Combination

“…Paradoxically, patients with exemplary dietary compliance in potassium restriction may be at greatest risk! The study by Chan et al 7 nicely illustrates the promise and the pitfalls of specialty-centric observational comparative effectiveness research, one component of a renewed federal commitment to patient-centered outcome studies. 8 For all of its strengths, the rich Fresenius database underlying the study necessarily is disease defined: The inception cohort begins with dialysis enrollment, and the variables are largely related to dialysis; although the study can compare patients according to digoxin levels, it cannot reliably measure digoxin indications or predialysis CHF management and cannot match patients who have CHF or atrial fibrillation and are treated with digoxin with those who are treated with other agents, such as ACEIs and ␤ blockers; that is, there may be immortal time bias in the data set.…”

“…Chan et al 7 conclude with the obligatory nod to safety evaluation in randomized trials. Unfortunately niche dialysis-specific trials for a generic drug never will happen.…”

“…The study by Chan et al 7 compares patients with and without digoxin treatment, using proportional hazards and propensity methods, but this approach is unconvincing to me despite good statistical analyses. Comparing digoxin and nondigoxin patients mostly just compares patients with and without heart failure and/or atrial fibrillation, with great risk for unmeasured confounding by severity and other cardiac comorbidities.…”

“…The mortality and morbidity of extended catheter use are well described. 7 The successful increase in late AVF use in the prevalent patient population of the United States is also associated with a substantial increase in catheter use, a result at least in part of nonpreemptive AVF placement. Preemptive placement of AVFs eliminates the cost and risk associated with prolonged catheter-based dialysis.…”