Predicting Cardiac Arrhythmias and Sudden Death in Diabetic Users of Proarrhythmic Drugs
- Marie L. De Bruin, PHD12,
- Tjeerd P. van Staa, PHD13,
- Svetlana V. Belitser, MSC1,
- Hubert G.M. Leufkens, PHD1 and
- Arno W. Hoes, MD2
- 1Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands
- 2Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, the Netherlands
- 3Environmental Epidemiology Unit, Medical Research Council, Southampton University Hospital, Southampton, U.K.
- Address correspondence and reprint requests to M.L. De Bruin, PharmD, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmacoepidemiology and Pharmacotherapy, P.O. Box 80082, 3508 TB Utrecht, Netherlands. E-mail: m.l.debruin{at}pharm.uu.nl
In diabetic patients, the corrected QT (QTc) interval is relatively long (1). In accordance with the concept of “reduced repolarization reserve” (2), a subsequent increase in QTc interval by proarrhythmic drugs may lead to cardiac arrhythmias and sudden death. Recently, it was shown that patients with diabetes are at increased risk of drug-induced arrhythmias (3). We developed a decision tool to predict the risk of serious ventricular arrhythmias and sudden death among diabetic users of nonantiarrhythmic proarrhythmic drugs.
RESEARCH DESIGN AND METHODS
A cohort study among 61,280 diabetic patients using nonantiarrhythmic proarrhythmic medication (amitriptyline, astemizole, chloroquine, chlorpromazine, cisapride, clarithromycin, clomipramine, cotrimoxazole, diphenhydramine/dimenhydrinate, domperidone, doxepine, droperidol, erythromycin, grepafloxacin, halofantrine, haloperidol, indapamide, ketanserin, lidoflazine, mianserine, pentamidine, pimozide, probucol, promethazine, protriptyline, sulfamethoxazole, sultopride, tacrolimus, terfenadine, terodiline, thioridazine, trimethoprim, and zimeldine) (4) in the General Practice Research Database (1987–2001) was performed. This database contains computerized medical records of ∼650 general practices, including ∼6.5% of the population of England and Wales. Diabetic patients were followed from the 1st day of prescription of any nonantiarrhythmic proarrhythmic drug. Follow-up was censored when the duration of (one of) the prescription(s) had elapsed, when the study outcome occurred, in case of death, upon exit from the study population, or at the end of the study period, whichever of these events came first. The combined study outcome included ventricular tachycardia, ventricular fibrillation and flutter, cardiac arrest, and sudden death. …
