Abstract
BackgroundResearch comparing sex differences in the effects of antipsychotic medications on acute ischemic heart disease (IHD) is limited and the findings ambiguous. This study aimed to investigate these associations within a primary care setting.MethodsHong Kong public general outpatient electronic records of patients aged 45+ during 2007–2010 were extracted, with the last consultation date as the baseline for a 4-year follow-up period to observe acute IHD hospitalizations (2011–2014). Antipsychotic use was defined as any prescription over the previous 12 months from a list of 16 antipsychotics, while acute IHD was defined by ICD-9: 410.00–411.89. Both sex-specific and sex-combined (both sexes) mixed-effects Cox models (random intercept across 74 clinics) were implemented to examine the association and test the interaction between antipsychotics and sex.ResultsAmong 1,043,236 included patients, 17,780 (1.7%) were prescribed antipsychotics, and 8342 (0.8%) developed IHD. In sex-specific analyses, antipsychotic prescription was associated with a 32% increased hazard rate of acute IHD among women (95% CI 1.05–1.67) but not among men. A likelihood ratio test comparing sex-combined models with and without the interaction between antipsychotic use and sex suggested significant interaction (χ2 = 4.72, P = 0.030). The association between antipsychotic use and IHD among women attenuated and became non-significant when haloperidol was omitted from the operationalization of antipsychotic use (HR = 1.23, 95% CI 0.95–1.60).ConclusionOur results suggest that antipsychotic prescription is moderately associated with an increased risk of acute IHD among women in primary care and this relationship may be explained by specific antipsychotics. Further research should observe and capture the potential intermediary mechanisms and the dose-response relationship of this association to provide more rigorous evidence to establish causality and inform clinical practices.
Highlights
Research comparing sex differences in the effects of antipsychotic medications on acute ischemic heart disease (IHD) is limited and the findings ambiguous
Antipsychotic medications commonly prescribed for patients with a variety of mental disorders such as schizophrenia, bipolar disorder, and dementia are generally believed to entail a heightened risk of acute ischemic heart disease (IHD) [1]
In this study, we identified a higher risk of acute IHD among Hong Kong Chinese middle-aged and older primary care recipients on antipsychotics, and this heightened risk was only evident among women but not among men
Summary
Research comparing sex differences in the effects of antipsychotic medications on acute ischemic heart disease (IHD) is limited and the findings ambiguous. In a review of 399,868 participants from nine observational studies [2], antipsychotic medications were found to be associated with 121%-elevated odds of myocardial infarction, whereas in another meta-analysis [3], no significant association was observed. These mixed findings may be due to a heterogeneity across study populations [4], suggesting that this association may only be present in populations with certain characteristics. This is because some mechanisms may operate more strongly in certain subpopulations, indicated by stronger statistical associations
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