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

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

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

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

Clinic visit-level bivariate analysis (N = 605239) according to the three sets of potentially inappropriate medication criteria.

<p>Abbreviations: MD- Medical Doctor, NTD- New Taiwan dollar.</p><p>***<i>P</i><0.001.</p

Characteristics of the three sets of explicit criteria and their performance in detecting potentially inappropriate medications.

<p>*Statements are those for potentially inappropriate medications without considering drug-disease or drug-syndrome interactions.</p

Multivariate logistic regression for having at least one potentially inappropriate medication in one clinic visit.

<p>***<i>P</i><0.0001.</p

Patient-level bivariate analysis (N = 25187) by the presence of least one PIM according to the three sets of potentially inappropriate medication criteria.

<p>***<i>P</i><0.0001.</p

Multivariate logistic regression for having at least one drug as potentially inappropriate.

<p>*<i>P</i><0.05,</p><p>**<i>P</i><0.01,</p><p>***<i>P</i><0.001.</p

Basic characteristics of the home healthcare recipients.

<p>Basic characteristics of the home healthcare recipients.</p