Risk of Mortality (including Sudden Cardiac Death) and Major Cardiovascular Events in Users of Olanzapine and Other Antipsychotics: A Study with the General Practice Research Database
Objective. Assess risk of cardiac events and mortality among users of olanzapine and other antipsychotics relative to nonusers. Methods. The General Practice Research Database was used to identify cohorts of antipsychotic users and nonusers with psychiatric illness. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Results. 183,392 antipsychotic users (including 20,954 olanzapine users) and 193,920 psychiatric nonusers were identified. There was a significantly higher rate of cardiac mortality (adjusted RR [aRR]: 1.53, CI, 1.12–2.09) in olanzapine users relative to psychiatric nonusers, consistent with findings for both atypical and typical antipsychotics. Relative to psychiatric nonusers, no increased risk of all-cause mortality was observed among olanzapine users (aRR: 1.04, CI, 0.93–1.17), but elevated all-cause mortality risk was observed when compared to all antipsychotic users (aRR: 1.75, CI, 1.64–1.87). There was no increased risk of CHD or VA among olanzapine users relative to psychiatric nonusers, consistent with findings for atypical but not typical antipsychotics. SCD cases were uncommon. Conclusions. Use of antipsychotic agents was associated with increased risk of all-cause and cardiac mortality. Patients treated with olanzapine were found to be at increased risk of cardiac mortality versus psychiatric nonusers. 1. Introduction It is generally accepted that that there is an increased risk of mortality (including sudden cardiac death (SCD)) and major cardiac events during treatment with some antipsychotics in patients with schizophrenia and other mental illnesses [1–5]. Several large observational studies have been conducted in recent years to assess the extent of increased risk with these outcomes in antipsychotic users and to differentiate risk with typical and atypical antipsychotics. In a retrospective cohort study of Medicaid enrollees in Tennessee, Ray et al. [2] found that current users of typical and atypical antipsychotics had a similar, dose-related increased risk of sudden cardiac death. The primary objective of the present retrospective observational study was to assess the risks of sudden cardiac death and cardiac mortality among users of the antipsychotic product olanzapine. The risk associated with olanzapine prescribing was assessed relative to psychiatric patients who did not use antipsychotic medications (nonusers) and among groups of antipsychotic medication users (atypical, typical, and any), as well as
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