Introduction: Unlike QT prolongation, drug-related QT shortening has recently emerged as a potential predictor of proarrhythmic risk, but its actual significance is unclear. Materials and Methods: Data mining approach was carried out on publicly accessible FDA spontaneous reports (January 2001-December 2009) to retrieve cases where QT shortening/prolongation was reported. The case-by-case analysis was performed on QT shortening and focused on suspected and concomitant drugs, co-reported arrhythmia-related events and severity of cases. Results: Among 1,644,133 total FDA reports, QT prolongation was reported in 3502 cases, whereas QT shortening only in 35 reports. Among cases reporting QT shortening, five drugs were reported twice as suspect (i. e. aripiprazole, atomoxetine, clozapine, moxifloxacin and ziprasidone). Digoxin and rufinamide (considered as QT shortening drugs), received one report each. In 10 cases, both QT shortening and prolongation were paradoxically reported and related to suspect drugs known for QT prolonging effect (i.e. arsenic trioxide, moxifloxacin, clarithromycin, cotrimoxazole, ziprasidone and sunitinib). Most cases (89%) were characterized by atrial and/or ventricular arrhythmias, with seven cases reporting potentially fatal events (i.e. ventricular fibrillation and/or cardiac arrest). Sixty-eight percent of cases were serious (i.e. causing death or hospitalization) and 70% occurred in females. Conclusion: These reports are consistent with the hypothesis that QT shortening may predict arrhythmias, although the clinical impact of QT shortening remains elusive and further investigation is needed. Pharmacovigilance reports should meet a common standard of ‘minimum requirements’ to become a more reliable indicator of risk. 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.

QT shortening among suspected adverse drug reactions reported to the FDA: a case-by-case analysis

RASCHI, EMANUEL;POLUZZI, ELISABETTA;KOCI, ARIOLA;BORIANI, GIUSEPPE;DE PONTI, FABRIZIO
2011

Abstract

Introduction: Unlike QT prolongation, drug-related QT shortening has recently emerged as a potential predictor of proarrhythmic risk, but its actual significance is unclear. Materials and Methods: Data mining approach was carried out on publicly accessible FDA spontaneous reports (January 2001-December 2009) to retrieve cases where QT shortening/prolongation was reported. The case-by-case analysis was performed on QT shortening and focused on suspected and concomitant drugs, co-reported arrhythmia-related events and severity of cases. Results: Among 1,644,133 total FDA reports, QT prolongation was reported in 3502 cases, whereas QT shortening only in 35 reports. Among cases reporting QT shortening, five drugs were reported twice as suspect (i. e. aripiprazole, atomoxetine, clozapine, moxifloxacin and ziprasidone). Digoxin and rufinamide (considered as QT shortening drugs), received one report each. In 10 cases, both QT shortening and prolongation were paradoxically reported and related to suspect drugs known for QT prolonging effect (i.e. arsenic trioxide, moxifloxacin, clarithromycin, cotrimoxazole, ziprasidone and sunitinib). Most cases (89%) were characterized by atrial and/or ventricular arrhythmias, with seven cases reporting potentially fatal events (i.e. ventricular fibrillation and/or cardiac arrest). Sixty-eight percent of cases were serious (i.e. causing death or hospitalization) and 70% occurred in females. Conclusion: These reports are consistent with the hypothesis that QT shortening may predict arrhythmias, although the clinical impact of QT shortening remains elusive and further investigation is needed. Pharmacovigilance reports should meet a common standard of ‘minimum requirements’ to become a more reliable indicator of risk. 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.
Special Issue: Abstracts of the 10th Congress of the European Association for Clinical Pharmacology and Therapeutics, 26-29 June 2011, Budapest, Hungary
56
164
E. Raschi; E. Poluzzi; A. Koci; G. Boriani; F. De Ponti
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/105643
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