Association Between Antipsychotic Use and Risk of Acute Myocardial Infarction: A Nationwide Case-Crossover Study

Study Questions:

What is the association between antipsychotic treatment and risk of acute myocardial infarction (AMI) in patients with mental disorders?

Methods:

The authors investigated the risk of AMI associated with antipsychotic treatment in 56,910 patients with schizophrenia, mood disorders, or dementia first hospitalized or visiting an emergency room for AMI in 1999-2009. A case-crossover design was used to compare the distributions of antipsychotic exposure for the same patient across 1-30 and 91-120 days just prior to the AMI event. Adjustments were made for co-medications and outpatient visits. Conditional logistic regression was used to estimate the association between risk of AMI, use of antipsychotics, and binding to receptors.

Results:

The adjusted odds ratio (AOR) of AMI risk was 2.52 (95% confidence interval [CI], 2.37-2.68) for any antipsychotics, 2.32 (95% CI, 2.17-2.47) for first-generation antipsychotics, and 2.74 (95% CI, 2.49-3.02) for second-generation antipsychotics. The risk significantly increased (p < 0.001) with elevations in dosage and in short-term use (≤30 days). Male patients, elderly patients, and patients with dementia were at significantly increased risk (all p < 0.001). Physically healthier patients with no pre-existing diabetes mellitus, hypertension, or dyslipidemia were at significantly greater risk (p < 0.001), largely because they had been exposed to higher doses of antipsychotics (p < 0.001). A study of the selected binding of antipsychotics to 14 neurotransmitter receptors revealed only dopamine type 3 receptor antagonism to be significantly associated with AMI risk (AOR, 2.59; 95% CI, 2.43-2.75; p < 0.0001).

Conclusions:

The authors concluded that antipsychotic use may be associated with a transient increase in risk for AMI, possibly mediated by dopamine type 3 receptor blockades.

Perspective:

This study reports that antipsychotic use in patients with schizophrenia, mood disorders, or dementia is significantly associated with risk for AMI. The risk was dose-dependent and increased in short-term users, male patients, elderly patients, and patients with dementia. Given the widespread use of antipsychotics in primary care and a lack of perception of such risk, clinicians need to be educated to start from low dosage of antipsychotics when such treatment is clearly indicated, followed by a close monitoring for the signs/symptoms of AMI, especially within the first 30 days of a treatment period. Because the dopamine type 3 receptor was found to be the most likely molecular target responsible for AMI associated with antipsychotic use, additional research is needed to investigate the possible underlying biological mechanisms of antipsychotic-related AMI. This may help in an effort to develop newer drugs which may not have this risk.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Hypertension, Sleep Apnea

Keywords: Antipsychotic Agents, Odds Ratio, Risk, Myocardial Infarction, Cross-Over Studies, Breast Neoplasms, Receptors, Dopamine, Dopamine Antagonists, Dopamine, Mental Disorders, Dyslipidemias, Schizophrenia, Receptors, Neurotransmitter, Outpatients, Dementia, Cardiovascular Diseases, Confidence Intervals, Hypertension, Logistic Models, Diabetes Mellitus, Primary Health Care


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