The QT interval and drug-induced torsades de pointes

Poster presentations

THE DRUG-INDUCED ARRHYTHMIA RISK EVALUATION (DARE) STUDY

^1,2V Marshall, ³E Behr, ³N Carter, ³S Jeffrey, ^1,2SAW Shakir, ³AJ Camm. ¹Drug Safety Research Unit, Southampton, UK; ²University of Portsmouth, Portsmouth, UK; ³St George’s University of London, London, UK

Proarrhythmia is a major public health issue for patients, prescribers and the pharmaceutical industry and the DARE study aims to recruit patients and controls prospectively in England to examine this phenomenon and evaluate the importance of predisposing epidemiological and genetic factors. The epidemiological arm of the study aims to systematically characterise incident cases of drug-induced arrhythmia and compare them with controls in order to assess the relative risks of predisposing factors and the long-term outcome. The genetic arm aims to determine whether mutations of cardiac ion channel genes and polymorphisms are more common in cases than controls. Patients with ventricular proarrhythmia are currently being recruited from cardiologists and all cases are confirmed for inclusion by an expert review panel. Three regional research nurses will have visited and interviewed patients and obtained copies of hospital and primary care (GP) records and ECGs and taken a blood sample and ECG. Population-based controls for the epidemiological arm of the study are being recruited for each case by random selection of four people for each case from an age-sex matched group provided by each case’s GP. DNA will be extracted from blood samples from epidemiological study cases and controls and undergo genetic testing for mutations and polymorphisms of implicated genes. An additional drug challenge will also be used in the genetic analysis. Thus the study is expected to improve the understanding of proarrhythmia and the predisposing risk factors including genetic risk and, furthermore, this collaborative study sets a precedent in setting up a nationwide registry characterising cases of the rare phenomenon of drug-induced arrhythmia. It …