QT-prolonging medications: prevalence of use and associated risks in CKD

Chronic kidney disease (CKD) affects over 10% of the global adult population and is associated with substantial cardiovascular morbidity and mortality. Sudden cardiac death (often precipitated by ventricular arrhythmias like torsades de pointes) is a leading cause of death in patients with CKD. Prolongation of the QT interval (a marker of delayed ventricular repolarization) is a significant risk factor for arrhythmia in patients with CKD, whether they are on dialysis or not. QT prolongation in CKD is multifactorial and may result from electrolyte imbalances, myocardial remodelling, autonomic dysfunction, and exposure to QT-prolonging drugs. Patients on haemodialysis are particularly vulnerable to QT prolongation, due to rapid intradialytic electrolyte and fluid shifts. Many drugs known to prolong the QT interval (including various selective serotonin reuptake inhibitors, antibiotics, antiemetics, and antipsychotics) are frequently prescribed to patients with CKD, even though there are few data on their safety in this population. The results of several well-designed pharmaco-epidemiological analyses (all based on data from the United States Renal Data System) have shown associations between QT-prolonging drugs and an elevated risk of sudden cardiac death among patients on dialysis. These findings are concerning, given the widespread use of such drug. The objective of this narrative review is to critically evaluate the pathophysiological relevance, prevalence, and cardiovascular consequences of QT-prolonging drug use in the CKD setting.