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QT-based pro-arrhythmia assessment remains unreliable in practice; leaves open the need for superior surrogates in drug development.
The ability of some non-cardiac drugs to alter cardiac repolarization and thereby increase the likelihood of cardiac arrhythmias, in particular life-threatening torsades de pointes, has led regulatory agencies to request that modifications of the QT interval, manifesting repolarization changes, should be intensively investigated in every drug developed. However, although prolongation of the QT interval is a relatively easily measured marker of repolarization changes, it is widely viewed as a poor surrogate of the arrhythmogenic potential of a drug. Despite intensive and costly investigation, the prediction of pro-arrhythmic risk based on pre-clinical and clinical data therefore remains imperfect. How QT interval relates to the safety of non-cardiac drugs, and how physicians can best integrate pre-clinical and clinical information in assessment of the risk profile of a drug, remain somewhat open questions.
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Kowey et al. (2007) studied this question.
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