Organising evidence on QT prolongation and occurrence of Torsades de Pointes with non-antiarrhythmic drugs: a call for consensus

Abstract.

Background: The growing list of non-antiarrhythmic drugs associated with QT prolongation and the relevant regulatory interventions have generated concern for two reasons. First, QT prolongation is sometimes viewed as an intrinsic effect of a whole therapeutic class (for example, antihistamines), whereas, in many cases, it is displayed only by some compounds within a given class of non-antiarrhythmic drugs because of an effect on cardiac repolarisation. Second, drug-induced Torsades de Pointes are still considered idiosyncratic, totally unpredictable adverse drug reactions, whereas a number of risk factors for their occurrence is now recognised. Objectives: In order to increase awareness among prescribing physicians that many non-antiarrhythmic drugs can affect cardiac repolarisation, we would like to propose a comprehensive and updated list of QT-prolonging drugs that should be a starting point to maintain a "consensus list" to be periodically updated. Methods: The drug list was generated by performing a Medline search, by using published lists as starting points to retrieve the relevant references quoted in each article and by considering the International Registry for Drug-induced Arrhythmias maintained by the Georgetown University and mainly based on the FDA approved labelling. Results: The drug list presented in this paper: (1) includes virtually all non-antiarrhythmic drugs with QT-prolonging potential, (2) organises the available information on each drug at different levels of clinical relevance and (3) is as up-to-date as possible in order to provide a fast track for the clinical pharmacologist to retrieve the original publications. Conclusions: This list should be considered as a starting point to call for consensus on: (1) the criteria used to generate the list, (2) possible ways to implement the use of this list as a quick reference for clinicians, for instance by providing a "proarrhythmic score" for each drug, and (3) inclusion/exclusion of a given agent into the list on the basis of evidence that may not be available to us.