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A correction has been published: N Engl J Med 2009;361(18):1814.
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Background Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice.
Methods We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs).
Results Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score.
Conclusions Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.
Source Information
From the Division of Pharmacoepidemiology, Department of Preventive Medicine (W.A.R., K.H.), the Divisions of Rheumatology (C.P.C., C.M.S.), Cardiology (K.T.M.), and Clinical Pharmacology (K.T.M., C.M.S.), Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine; and the Geriatric Research, Education, and Clinical Center, Nashville Veterans Affairs Medical Center (W.A.R.) — both in Nashville.
Address reprint requests to Dr. Ray at the Department of Preventive Medicine, Village at Vanderbilt, Suite 2600, 1501 21st Ave. South, Nashville, TN 37212, or at cindy.naron{at}vanderbilt.edu.
Related Letters:
Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death
Baldessarini R. J., Price L. H., Ray W. A., Murray K. T., Stein C. M.
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N Engl J Med 2009;
360:2136-2138, May 14, 2009.
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