PURPOSE: The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening. METHODS: By using a self-controlled crossover study with 59 467 subjects, we ascertained intra-individual change in log-linear regression-corrected QT (QTcreg ) during the period between 1995 and mid-2008 for 90 drugs while adjusting for age, gender, race/ethnicity, comorbid conditions, number of electrocardiograms (ECGs), and time between pre-ECG and post-ECG. The proportion of users of each drug-developing incident long QT was also estimated. RESULTS: Two drugs (nicardipine and levalbuterol) had no statistically significant intra-individual QTcreg shortening effects, 10 drugs had no statistically significant prolonging effect, and 78 (87%) of the drugs had statistically significant intra-individual mean QTcreg lengthening effects, ranging from 7.6 ms for aripiprazole to 25.2 ms for amiodarone. Three drugs were associated with mean QTcreg prolongation of 20 ms or greater: amiodarone (antiarrhythmic), terfenadine (antihistaminic), and quinidine (antiarrhythmic); whereas 11 drugs were associated with mean QTcreg prolongation of 15 ms or greater but less than 20 ms: trimipramine (tricyclic antidepressant), clomipramine (tricyclic antidepressant), disopyramide (antiarrhythmic), chlorpromazine (antipsychotic), sotalol (beta blocker), itraconazole (antifungal), phenylpropanolamine (decongestant/anorectic), fenfluramine (appetite suppressant), midodrine (antihypotensive), digoxin (cardiac glycoside/antiarrhythmic), and procainamide (antiarrhythmic). CONCLUSIONS: QT prolonging effects were common and varied in strength. Our results lend support to past Food and Drug Administration regulatory actions and support the role for ongoing surveillance of drug-induced QT prolongation.
PURPOSE: The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening. METHODS: By using a self-controlled crossover study with 59 467 subjects, we ascertained intra-individual change in log-linear regression-corrected QT (QTcreg ) during the period between 1995 and mid-2008 for 90 drugs while adjusting for age, gender, race/ethnicity, comorbid conditions, number of electrocardiograms (ECGs), and time between pre-ECG and post-ECG. The proportion of users of each drug-developing incident long QT was also estimated. RESULTS: Two drugs (nicardipine and levalbuterol) had no statistically significant intra-individual QTcreg shortening effects, 10 drugs had no statistically significant prolonging effect, and 78 (87%) of the drugs had statistically significant intra-individual mean QTcreg lengthening effects, ranging from 7.6 ms for aripiprazole to 25.2 ms for amiodarone. Three drugs were associated with mean QTcreg prolongation of 20 ms or greater: amiodarone (antiarrhythmic), terfenadine (antihistaminic), and quinidine (antiarrhythmic); whereas 11 drugs were associated with mean QTcreg prolongation of 15 ms or greater but less than 20 ms: trimipramine (tricyclic antidepressant), clomipramine (tricyclic antidepressant), disopyramide (antiarrhythmic), chlorpromazine (antipsychotic), sotalol (beta blocker), itraconazole (antifungal), phenylpropanolamine (decongestant/anorectic), fenfluramine (appetite suppressant), midodrine (antihypotensive), digoxin (cardiac glycoside/antiarrhythmic), and procainamide (antiarrhythmic). CONCLUSIONS: QT prolonging effects were common and varied in strength. Our results lend support to past Food and Drug Administration regulatory actions and support the role for ongoing surveillance of drug-induced QT prolongation.
Authors: A A Seyerle; C M Sitlani; R Noordam; S M Gogarten; J Li; X Li; D S Evans; F Sun; M A Laaksonen; A Isaacs; K Kristiansson; H M Highland; J D Stewart; T B Harris; S Trompet; J C Bis; G M Peloso; J A Brody; L Broer; E L Busch; Q Duan; A M Stilp; C J O'Donnell; P W Macfarlane; J S Floyd; J A Kors; H J Lin; R Li-Gao; T Sofer; R Méndez-Giráldez; S R Cummings; S R Heckbert; A Hofman; I Ford; Y Li; L J Launer; K Porthan; C Newton-Cheh; M D Napier; K F Kerr; A P Reiner; K M Rice; J Roach; B M Buckley; E Z Soliman; R de Mutsert; N Sotoodehnia; A G Uitterlinden; K E North; C R Lee; V Gudnason; T Stürmer; F R Rosendaal; K D Taylor; K L Wiggins; J G Wilson; Y-Di Chen; R C Kaplan; K Wilhelmsen; L A Cupples; V Salomaa; C van Duijn; J W Jukema; Y Liu; D O Mook-Kanamori; L A Lange; R S Vasan; A V Smith; B H Stricker; C C Laurie; J I Rotter; E A Whitsel; B M Psaty; C L Avery Journal: Pharmacogenomics J Date: 2017-07-18 Impact factor: 3.550
Authors: Neha Mantri; Meng Lu; Jonathan G Zaroff; Neil Risch; Thomas Hoffmann; Akinyemi Oni-Orisan; Catherine Lee; Carlos Iribarren Journal: Ann Noninvasive Electrocardiol Date: 2021-09-21 Impact factor: 1.468