Use of QT Prolonging Medications by Hemodialysis Patients and Individuals Without End-Stage Kidney Disease

Abstract

Background The rate of sudden cardiac death in the hemodialysis population exceeds that of the general population by >20-fold. Hemodialysis patients may be particularly susceptible to sudden cardiac death provoked by drug-induced QT prolongation because of their substantial cardiovascular disease burden, exposure to electrolyte shifts during dialysis, and extensive polypharmacy. However, population-specific data regarding the frequency and patterns of QT prolonging medication use are limited. Methods and Results We conducted a descriptive drug utilization study using 3 administrative databases, the United States Renal Data System, MarketScan, and Medicare claims. We characterized the extent and patterns of QT prolonging medication use by adult hemodialysis patients and individuals without end-stage kidney disease annually from 2012 to 2016. We also identified instances of high-risk QT prolonging medication use among hemodialysis patients. In total, 338 515 hemodialysis patients and 40.7 million individuals without end-stage kidney disease were studied. Annual utilization rates of QT prolonging medications with known torsades de pointes risk in hemodialysis patients were ~1.4 to ~2.5 times higher than utilization rates in individuals without end-stage kidney disease. Hemodialysis patients with demographic and clinical risk factors for drug-induced QT prolongation were exposed to medications with known torsades de pointes risk more often than patients without risk factors. Conclusions Hemodialysis patients use QT prolonging medications with known torsades de pointes risk more extensively than individuals without end-stage kidney disease. Given the widespread use and instances of high-risk prescribing, future studies evaluating the cardiac safety of these drugs in the hemodialysis population are needed.

Keywords: Hemodialysis; QT prolonging medications; patterns of use.

Figure 1. Use of ≥1 prescription QT prolonging medication by the hemodialysis and non‐ESKD populations, 2012 to 2016.

A and B, Depict annual standardized rates of exposure to ≥1 QT prolonging medication in the younger hemodialysis and non‐ESKD populations, respectively. C and D, Depict analogous annual rates of QT prolonging medication exposure in the older hemodialysis and non‐ESKD populations. CredibleMeds classifies medications that can prolong the QT interval as having a known, possible, or conditional TdP risk. Corresponding definitions are provided in Table 1 and lists of medications falling into each category are provided in Table S3. Medications classified as having any TdP risk are those falling into any of the 3 CredibleMeds categories. ESKD indicates end‐stage kidney disease; and TdP, torsades de pointes.

Figure 2. Use of ≥1 prescription medication with known TdP risk by hemodialysis patients with and without risk factors for drug‐induced QT prolongation in 2016.

A, Depicts standardized rates of exposure to ≥1 medication with known TdP risk by hemodialysis patients with and without risk factors for drug‐induced QT prolongation. B, Depicts analogous rates of exposure to ≥1 non‐antiarrhythmic medication with known TdP risk in each subgroup. Medications with known TdP risk are listed in Table S3. Advanced age was defined as ≥65 years of age.9 TdP indicates torsades de pointes.

Figure 3. Concurrent use of medications with known TdP risk by the 2016 hemodialysis population.

Values presented are crude rates of exposure to a given medication combination expressed as the number of days exposed per person‐year. TdP indicates torsades de pointes.

Figure 4. Concurrent use of CYP metabolized medications with known risk TdP risk and relevant metabolic inhibitors by the 2016 hemodialysis population.

Values presented are crude rates of exposure to a given medication combination expressed as the number of days exposed per person‐year. Of the top 5 medications with a known TdP risk used by the adult hemodialysis population, amiodarone, citalopram, escitalopram, and ondansetron are major substrates of cytochrome isoenzymes. An “X” on the figure indicates that the QT prolonging medication is not a major substrate of specified CYP isoenzyme. Relevant CYP inhibitors are listed in Table S4. CYP indicates cytochrome P450; and TdP, torsades de pointes.