Antipsychotic Medications and Risk of Acute Coronary Syndrome in Schizophrenia: A Nested Case-Control Study

<div><p>Background</p><p>This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients.</p><p>Methods</p><p>A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147) were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association.</p><p>Results</p><p>We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27–10.64, p<0.05) and chlorpromazine (adjusted RR = 2.96, 95% CI: 1.40–6.24, p<0.001) were associated with a dose-dependent increase in the risk of developing acute coronary syndrome. Although haloperidol was associated with an increased risk (adjusted RR = 2.03, 95% CI: 1.20–3.44, p<0.01), there was no clear dose-dependent relationship. These three antipsychotic agents were also associated with an increased risk in the first 30 days of use, and the risk decreased as the duration of therapy increased. Sensitivity analyses using propensity score-adjusted modeling showed that the results were similar to those of multiple regression analysis.</p><p>Conclusions</p><p>Patients with schizophrenia who received aripiprazole, chlorpromazine, or haloperidol could have a potentially elevated risk of developing acute coronary syndrome, particularly at the start of therapy.</p></div

Characteristics of case patients with acute coronary syndrome and control patients derived from a nationwide cohort with schizophrenia (N = 31,177).

Characteristics of case patients with acute coronary syndrome and control patients derived from a nationwide cohort with schizophrenia (N = 31,177).</p

Duration of therapy and dose of individual antipsychotic agents by case patients with acute coronary syndrome and controls.

<p>Duration of therapy and dose of individual antipsychotic agents by case patients with acute coronary syndrome and controls.</p

Association between the current use of each second- or first-generation antipsychotic agent and the risk of acute coronary syndrome relative to the noncurrent use of antipsychotic agent (reference group).

<p>Association between the current use of each second- or first-generation antipsychotic agent and the risk of acute coronary syndrome relative to the noncurrent use of antipsychotic agent (reference group).</p

Risk of acute coronary syndrome and effect of cumulative days of continuous antipsychotic treatment (no use as the reference group).

<p>Risk of acute coronary syndrome and effect of cumulative days of continuous antipsychotic treatment (no use as the reference group).</p

Blepharitis cohort to non-blepharitis cohort incidence rate ratio of anxiety and depression by quartile of follow-up years.

<p>Blepharitis cohort to non-blepharitis cohort incidence rate ratio of anxiety and depression by quartile of follow-up years.</p

Incidence rates by sex, age and cohort, and blepharitis cohort to non-blepharitis cohort rate ratios and Cox model measured hazard ratios.

<p>PY, person-years; Rate^#, incidence per 1,000 person-years; IRR*, incidence rate ratio.</p><p>Adjusted HR^†: adjusted for age, sex, diabetes, hyperlipidemia, hypertension, coronary artery disease and stroke.</p><p>*p<0.05.</p><p>**p<0.01.</p

Incidence of depression and anxiety, blepharitis cohort to non-blepharitis cohort rate ratio and Cox model measured hazards ratio by comorbidity.

<p>Rate^#, incidence rate, per 1,000 person-years; IRR*, incidence rate ratio.</p><p>Adjusted HR^†: adjusted for age, sex, diabetes, hyperlipidemia, hypertension, coronary artery disease and stroke.</p><p>*p<0.05.</p><p>**p<0.01.</p

Demographic characteristics and comorbidities in blepharitis cohort and non-blepharitis cohort.

<p>&:Chi-square test; t-test used to test means.</p

Distribution of Physical Illnesses among Cases with Short-Term Mortality and Controls.

<p>Distribution of Physical Illnesses among Cases with Short-Term Mortality and Controls.</p