[The importance of electrocardiography in the development of new drugs--prolonged QT intervals as indicators of adverse effects].
Both experimental animal studies and clinical observations have shown that drugs from various indication areas, such as psychotropic agents and antiarrhythmics can induce disturbances of cardiac rhythm and electrocardiographic abnormalities. Particularly, QT interval prolongation is associated with distinctive polymorphic ventricular tachycardias and often causes syncopes or cardiac arrest that represent a high risk of recurrent events including sudden death. In the last decade, several drugs in different indication areas, possessing these effects were withdrawn from the market and approvals were postponed or even refused. These events led to higher regulatory requirements on the cardiovascular safety of new drugs, with a special emphasis on prolongation of the QT interval. This article reviews the use of preclinical and clinical electrocardiography, as well as the current problems during development of novel drugs and future strategy in clinical studies. Even though ECG proved to be a powerful and reliable tool for detection of cardiac serious adverse effects during development of drugs, it also needs to be used with increased attention in all patients treated with new drugs and drug combinations in clinical and ambulatory practice in order to ensure their safe use in a wide population, as well as in patients with concurrent cardiac risk factors.
Novartis Pharma AG., Basel, Svýcarsko.
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D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography; D006801:Humans