Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death

University of Groningen, Groningen, Groningen, Netherlands
European Heart Journal (Impact Factor: 15.2). 11/2005; 26(19):2007-12. DOI: 10.1093/eurheartj/ehi312
Source: PubMed


To assess the association between the use of non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death.
A population-based case-control study was performed in the Integrated Primary Care Information (IPCI) project, a longitudinal observational database with complete medical records from more than 500,000 persons. All deaths between 1 January 1995 and 1 September 2003 were reviewed. Sudden cardiac death was classified based on the time between onset of cardiovascular symptoms and death. For each case, up to 10 random controls were matched for age, gender, date of sudden death, and general practice. The exposure of interest was the use of non-cardiac QTc-prolonging drugs. Exposure at the index date was categorized into three mutually exclusive groups of current use, past use, and non-use. The study population comprised 775 cases of sudden cardiac death and 6297 matched controls. Current use of any non-cardiac QTc-prolonging drug was associated with a significantly increased risk of sudden cardiac death (adjusted OR: 2.7; 95% CI: 1.6-4.7). The risk of death was highest in women and in recent starters.
The use of non-cardiac QTc-prolonging drugs in a general population is associated with an increased risk of sudden cardiac death.

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Available from: Sabine Straus, Mar 11, 2015
    • "Additionally, in the case of successful development , a precaution-free regulatory approval would have been virtually impossible to obtain, even in the absence of clinical evidence of proarrhythmic danger (e.g., ranolazine). Available human data demonstrate that only compounds producing a marked blockade of the cardiac hERG channel accompanied by excessive prolongation of ventricular repolarization (QTc interval prolongation N 500 ms) portend a potentially lethal TdP risk in people generally carrying additional cardiac risks (Straus et al., 2005). Small to moderate QTc prolongations are unlikely to elicit TdP events, particularly when produced by drugs (e.g.; fluoxetine , ranolazine and verapamil) which concurrently block cardiac depolarization currents (I NaL and I Ca ), that have the ability to constrain hERG blockade-mediated QTc prolongation to non-dangerous levels (Antzelevitch et al., 2014; Moreno and Clancy, 2012). "
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    No preview · Article · Jul 2015 · Journal of pharmacological and toxicological methods
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    • "Two case-control studies from the Netherlands [46] [47] examined the relation of SCD or in-hospital cardiac arrest to exposure to noncardiac QTc-prolonging medications. One study found an almost four-fold increased risk of out-of-hospital SCD among current users of domperidone [46]. "
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    • "E14, 2005). Drugs that prolong or shorten the QT interval in the ECG are considered to have pro-arrhythmic consequences (Straus et al., 2005; Kowey and Malik, 2007; Lu et al., 2008; Pugsley et al., 2008), and their development is generally discontinued. "
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