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Antipsychotics and the Risk of Sudden Cardiac Death
Sabine M. J. M. Straus, MD;
Gysèle S. Bleumink, MD;
Jeanne P. Dieleman, PhD;
Johan van der Lei, MD, PhD;
Geert W. ‘t Jong, PhD;
J. Herre Kingma, MD, PhD;
Miriam C. J. M. Sturkenboom, PhD;
Bruno H. C. Stricker, PhD
Arch Intern Med. 2004;164:1293-1297.
Background Antipsychotics have been associated with prolongation of the corrected QT interval and sudden cardiac death. Only a few epidemiological studies have investigated this association. We performed a case-control study to investigate the association between use of antipsychotics and sudden cardiac death in a well-defined community-dwelling population.
Methods We performed a population-based case-control study in the Integrated Primary Care Information (IPCI) project, a longitudinal observational database with complete medical records from 150 general practitioners. All instances of death between January 1, 1995, and April 1, 2001, were reviewed. Sudden cardiac death was classified based on time between onset of cardiovascular symptoms and death. For each case, up to 10 random controls were matched for age, sex, date of sudden death, and practice. Exposure at the index date was categorized as 3 mutually exclusive groups of current use, past use, and nonuse.
Results The study population comprised 554 cases of sudden cardiac death. Current use of antipsychotics was associated with a 3-fold increase in risk of sudden cardiac death. The risk of sudden cardiac death was highest among those using butyrophenone antipsychotics, those with a defined daily dose equivalent of more than 0.5 and short-term ( 90 days) users. The association with current antipsychotic use was higher for witnessed cases (n = 334) than for unwitnessed cases.
Conclusions Current use of antipsychotics in a general population is associated with an increased risk of sudden cardiac death, even at a low dose and for indications other than schizophrenia. Risk of sudden cardiac death was highest among recent users but remained elevated during long-term use.
From the Pharmaco-epidemiology Unit, Departments of Epidemiology & Biostatistics and Internal Medicine (Drs Straus, Bleumink, Dieleman, Sturkenboom, and Stricker) and Department of Medical Informatics (Drs Straus, Dieleman, van der Lei, ‘t Jong, and Sturkenboom), Erasmus Medical Center, Rotterdam, the Netherlands; Medicines Evaluation Board, the Hague, the Netherlands (Dr Kingma); Inspectorate for Health Care, the Hague (Drs Bleumink and Stricker); and the Department of Clinical Pharmacology, University of Groningen, Groningen, the Netherlands (Dr Kingma). Dr Sturkenboom acted in a consultant capacity for Lundbeck SA (France) regarding the safety of an atypical antipsychotic (sertindole) and appeared before the Committee of Proprietary Medicinal Products (CPMP) regarding the safety of sertindole. Dr Sturkenboom is responsible for scientific research conducted with the IPCI database in the Netherlands, which is supported by project-specific grants from various pharmaceutical companies: GlaxoSmithKline, AstraZeneca, Merck, Pharmacia, Sanofi, Pfizer, Schering, Bristol-Meyers-Squibb, EliLilly, Wyeth, and Yamanouchi. None of the projects concern antipsychotics.
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