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

Cardiac Complications Associated with Short-Term Mortality in Schizophrenia Patients Hospitalized for Pneumonia: A Nationwide Case-Control Study

<div><p>Background</p><p>Pneumonia is one of most prevalent infectious diseases worldwide and is associated with considerable mortality. In comparison to general population, schizophrenia patients hospitalized for pneumonia have poorer outcomes. We explored the risk factors of short-term mortality in this population because the information is lacking in the literature.</p><p>Methods</p><p>In a nationwide schizophrenia cohort, derived from the National Health Insurance Research Database in Taiwan, that was hospitalized for pneumonia between 2000 and 2008 (n = 1,741), we identified 141 subjects who died during their hospitalizations or shortly after their discharges. Based on risk-set sampling in a 1∶4 ratio, 468 matched controls were selected from the study cohort (i.e., schizophrenia cohort with pneumonia). Physical illnesses were categorized as pre-existing and incident illnesses that developed after pneumonia respectively. Exposures to medications were categorized by type, duration, and defined daily dose. We used stepwise conditional logistic regression to explore the risk factors for short-term mortality.</p><p>Results</p><p>Pre-existing arrhythmia was associated with short-term mortality (adjusted risk ratio [RR] = 4.99, p<0.01). Several variables during hospitalization were associated with increased mortality risk, including incident arrhythmia (RR = 7.44, p<0.01), incident heart failure (RR = 5.49, p = 0.0183) and the use of hypoglycemic drugs (RR = 2.32, p<0.01). Furthermore, individual antipsychotic drugs (such as clozapine) known to induce pneumonia were not significantly associated with the risk.</p><p>Conclusions</p><p>Incident cardiac complications following pneumonia are associated with increased short-term mortality. These findings have broad implications for clinical intervention and future studies are needed to clarify the mechanisms of the risk factors.</p></div

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

Basic characteristics of the home healthcare recipients.

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