Purpose: Prolonged ventricular repolarization (measured as heart-rate corrected QT (QTc) prolongation or JT-interval prolongation) is a risk factor for ventricular arrhythmias and can be drug-induced. Drugs can be classified as having known or possible QTc-prolonging properties. Regulatory agencies recommend avoiding concomitant use of multiple QTc-prolonging drugs, but evidence is lacking to what degree ventricular repolarization is influenced by concomitant use of these drugs. Methods: Within a population-based cohort of persons aged 45years and older, with up to five electrocardiograms recorded per participant between 1991 and 2010, we used generalised estimating equations to study the association between concomitant use of multiple QTc-prolonging drugs and repolarization duration. Results: The study population consisted of 13009 participants with 26908 electrocardiograms. With the addition of a second or third QTc-prolonging drug there was no substantial increase in QTc and JT interval and no increased risk of a prolonged QTc interval, compared to use of one QTc-prolonging drug. There was a large difference between the effect of one known or one possible QTc-prolonging drugs on QTc interval: 15ms for known, and 3ms for possible QTc-prolonging drugs. Conclusions: In this study, the added prolongation in users of two or three QTc-prolonging drugs on QTc was small. There was a large difference in QTc prolongation between known and possible QTc-prolonging drugs. Further research in larger or high-risk populations is needed to establish whether it is safe to use multiple QTc-prolonging drugs concomitantly to prevent that the current advice might unnecessarily withhold beneficial drugs from patients.

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Keywords Epidemiology, JT interval, Pharmacoepidemiology, Population based, QT interval, QT-prolonging drugs, Ventricular repolarization
Persistent URL dx.doi.org/10.1002/pds.3853, hdl.handle.net/1765/88011
Journal Pharmacoepidemiology and Drug Safety: an international journal
Niemeijer, M.N, van den Berg, M.E, Franco, O.H, Hofman, A, Kors, J.A, Stricker, B.H.Ch, … Rijnbeek, P.R. (2015). Drugs and ventricular repolarization in a general population: The Rotterdam Study. Pharmacoepidemiology and Drug Safety: an international journal, 24(10), 1036–1041. doi:10.1002/pds.3853