Risk of Mortality (Including Sudden Cardiac Death) and Major Cardiovascular Events in Atypical and Typical Antipsychotic Users: A Study with the General Practice Research Database
Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87); cardiac mortality 1.72 (95% CI: 1.42–2.07); SCD primary definition 5.76 (95% CI: 2.90–11.45); SCD secondary definition 2.15 (95% CI: 1.64–2.81); CHD 1.16 (95% CI: 0.94–1.44); and VA 1.16 (95% CI: 1.02–1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85); cardiac mortality 0.89 (95% CI: 0.82–0.97); and SCD secondary definition 0.76 (95% CI: 0.55–1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort. 1. Introduction Antipsychotics used for the treatment of schizophrenia and other mental illnesses have been associated with increased mortality (including sudden cardiac death) and major cardiac events. Several observational studies have assessed this association [1–4]. A retrospective cohort study of Medicaid enrollees in Tennessee found that for current users of both typical and atypical antipsychotics the risk of sudden cardiac death increased with increasing dose [4]. Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1.03–2.46) for those taking low doses to 2.86 (95% CI, 2.25–3.65) for those taking high doses. Limitations of the study included the inability to fully control for major potential confounders (e.g., increasing disease severity with increasing dose, untreated psychosis, unhealthy lifestyle,
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