Reporting frequency of QT-interval abnormalities in the FDA Adverse Event Reporting System (FDA_AERS).

Introduction: QT prolongation is a recognized surrogate marker of proarrhythmia, namely Torsade de Pointes (TdP). Recently, interest has emerged on the possible arrhythmic risk associated with QT shortening. Materials and Methods: From the publicly accessible FDA_AERS (January 2001-December 2009), spontaneous reports of TdP, QT prolongation/shortening were selected. The reporting frequency (restricted to drugs reported as suspect) was provided for top five agents by calculating the ratio between cases of interest and other reports in the database. The list was analyzed according to Arizona_CERT current information (www.azcert.org). Results: From 1,644,133 total FDA reports, TdP was identified in 1482 cases (0.009%), QT prolongation in 3502 (0.002%), whereas QT shortening only in 35 reports (with 30 reported drugs). The reporting frequency for TdP was: cisapride (10.7%, 77 cases), sotalol (9.9%, 70), methadone (4.1%, 143), fluconazole (3.9%, 91), amiodarone (3.4%, 160). The rank for QT prolongation was: cisapride (38.7%, 223 cases), arsenic trioxide (13.5% 83), sotalol (10.7%, 75), nilotinib (10.6%, 94), methadone (4.3%, 150). All agents are grouped in the ‘Torsades List’ of the Arizona_CERT website, except fluconazole (‘Conditional Torsades List’). Rufinamide and digoxin (considered as QT shortening drugs) received only one report each. Conclusion: The reporting frequencies of TdP and QT prolongation involved similar drugs and are in line with information reported by Arizona_CERT, although fluconazole deserves further investigation regarding its pro-arrhythmic risk. The clinical impact of QT shortening remains elusive. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n 241679 – the ARITMO project.