Reckless administration of QT interval-prolonging agents in elderly patients with drug-induced torsade de pointes

Abstract

A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome, female gender and congestive heart failure), modifiable risk factors (e.g. hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless administration of a QT interval-prolonging agent (e.g. despite a known QT interval prolongation or a history of TdP, together with other QT interval prolonging agents in higher than recommended doses) were recorded in each case. Overall, 54 (88.5%) patients had non-modifiable risk factors for drug-induced TdP and 21 (34.4%) patients had modifiable risk factors. The administration of the offending agent was reckless in one half (n = 31; 50.8%) of the patients. The most prevalent reckless administration of a QT interval-prolonging agent was together with other QT interval-prolonging agents (n = 16; 51.6%) or despite QT interval prolongation (n = 8; 25.8%). In conclusion, although risk factors for drug-induced TdP are prevalent in elderly patients with drug-induced TdP, in approximately 50% of patients it appeared following a reckless administration of a QT interval-prolonging agent. In this population physicians should particularly avoid administration of two or more QT interval-prolonging agents simultaneously or administration of a QT interval-prolonging agent despite QT interval prolongation.

Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders

“…Drug labels recommend against administration of quetiapine or ziprasidone in combination with other drugs that are known to prolong QT interval and in people with bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval (114,115). Despite these recommendations, prevalence of polypharmacy with multiple pro-arrhythmic drugs is high (2,4,101).…”

“…Novel technology applications and adequate statistical methods should be used for routine analysis of antipsychotic-induced QT prolongation and cardiac arrhythmias. [71] Female [38], Male [26] 20+ [49], <20 [2] Risperidone Electrocardiogram QT corrected interval prolonged [43] Female [23], Male [20] 20+ [26], <20 [4] Ziprasidone Hydrochloride Torsade de pointes [83] Female [61], Male [19] 20+ [57] Ziprasidone Hydrochloride…”

“…Observational studies provide consistent evidence that prolonged QT interval is associated with higher risk of all-cause and cardiovascular mortality (1). Drug-induced prolongation of QT contributes to higher mortality (2,3).…”

Effects of antidepressants on QT interval in people with mental disorders

“…Drug labels recommend against administration of antidepressants in combination with other drugs that are known to prolong QT interval and in people with bradycardia, hypokalemia or hypomagnesemia, or congenital prolongation of the QT interval [9, 11-21, 115, 117]. Despite these recommendations, the prevalence of polypharmacy with multiple proarrhythmic drugs is high [2,4,136].…”

“…Observational studies provide consistent evidence that prolonged QT interval is associated with higher risk of all-cause and cardiovascular mortality [1]. Drug-induced prolongation of QT contributes to higher mortality [2,3]. The risk of drug-induced prolongation of QT is much higher in older adults and people with multiple chronic conditions [4].…”