title: Drugs and ventricular repolarization in a general population: the Rotterdam Study.
abstract: OBJECTIVE
  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 45 years 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 13 009 participants with 26 908 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: 15 ms for known, and 3 ms 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.
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Maartje N
authors.initials: MN
authors.lastname: Niemeijer
authors.affiliation: Department of Medical Informatics, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Marten E
authors.initials: ME
authors.lastname: van den Berg
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Medical Informatics, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kors
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.|Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.|Inspectorate of Health Care, Utrecht, the Netherlands.
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.affiliation: Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.|Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Eijgelsheim
authors.affiliation: Department of Medical Informatics, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Rijnbeek
mesh_terms: D000368:Aged; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D017891:Pharmacoepidemiology; D011446:Prospective Studies
keywords: JT interval; QT interval; QT-prolonging drugs; epidemiology; pharmacoepidemiology; population based; ventricular repolarization