title: Time-to-Onset Analysis of Drug-Induced Long QT Syndrome Based on a Spontaneous Reporting System for Adverse Drug Events.
abstract: Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database. For signal detection, we used the reporting odds ratio (ROR). Furthermore, we analyzed the time-to-onset data and assessed the hazard type using the Weibull shape parameter. The RORs (95% confidence interval) for bepridil, amiodarone, pilsicainide, nilotinib, disopyramide, arsenic trioxide, clarithromycin, cibenzoline, donepezil, famotidine, sulpiride, and nifekalant were 174.4 (148.6-204.6), 17.3 (14.7-20.4), 52.0 (43.4-62.4), 13.9 (11.5-16.7), 69.3 (55.3-86.8), 54.2 (43.2-68.0), 4.7 (3.8-5.8), 19.9 (15.9-25.0), 8.1 (6.5-10.1), 3.2 (2.5-4.1), 7.1 (5.5-9.2), and 254.8 (168.5-385.4), respectively. The medians and quartiles of time-to-onset for aprindine (oral) and bepridil were 20.0 (11.0-35.8) and 18.0 (6.0-43.0) days, respectively. The lower 95% confidence interval of the shape parameter β of bepridil was over 1 and the hazard was considered to increase over time.Our study indicated that the pattern of LQTS onset might differ among drugs. Based on these results, careful long-term observation is recommended, especially for specific drugs such as bepridil and aprindine. This information may be useful for the prevention of sudden death following LQTS and for efficient therapeutic planning.
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sasaoka
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hane
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.|Medical database Co., LTD, Shibuya-ku, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Abe
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Motooka
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Hatahira
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Akiho
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Naganuma
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu-shi, Gifu, Japan.
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kinosada
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
authors.forename: Mitsuhiro
authors.identifier: http://orcid.org/0000-0002-5062-5522
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000284:Administration, Oral; D001073:Aprindine / Q000008:administration & dosage / Q000009:adverse effects*; D015764:Bepridil / Q000008:administration & dosage / Q000009:adverse effects*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D013997:Time Factors
chemical_list: D001073:Aprindine; D015764:Bepridil