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European Heart Journal Advance Access published online on May 11, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi312
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European Heart Journal © The European Society of Cardiology 2005; All rights reserved
Received February 6, 2005
Revised April 1, 2005
Accepted April 7, 2005

Clinical research

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

Sabine M.J.M. Straus 1, Miriam C.J.M. Sturkenboom 2, Gysèle S. Bleumink 3, Jeanne P. Dieleman 2, Johan van der Lei 4, Pieter A. de Graeff 5, Jan Herre Kingma 6, and Bruno H.Ch. Stricker 7*

1 Pharmaco-Epidemiology Unit, Departments of Epidemiology and Biostatistics and Internal Medicine, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Medical Informatics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands; Medicines Evaluation Board, The Hague, The Netherlands
2 Pharmaco-Epidemiology Unit, Departments of Epidemiology and Biostatistics and Internal Medicine, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Medical Informatics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands
3 Pharmaco-Epidemiology Unit, Departments of Epidemiology and Biostatistics and Internal Medicine, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands
4 Department of Medical Informatics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands
5 Medicines Evaluation Board, The Hague, The Netherlands; Department of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands
6 Inspectorate for Health Care, The Hague, The Netherlands; Department of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands
7 Pharmaco-Epidemiology Unit, Departments of Epidemiology and Biostatistics and Internal Medicine, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands

* To whom correspondence should be addressed.
Bruno H.Ch. Stricker, E-mail: b.stricker{at}erasmusmc.nl


  Abstract

Aims To assess the association between the use of non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death.

Methods and results 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.

Conclusion The use of non-cardiac QTc-prolonging drugs in a general population is associated with an increased risk of sudden cardiac death.

Keywords: Sudden cardiac death; Non-cardiac QTc-prolonging drugs; Pharmaco-epidemiology; Population based.
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