Association Between Antipsychotic Use and Risk of Acute Myocardial Infarction: A Nationwide Case-Crossover Study
Background—Antipsychotic medications have been increasingly and more widely prescribed despite continued uncertainty about their association with incidence of acute myocardial infarction (AMI).
Methods and Results—We 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. The adjusted odds ratio (AOR) of AMI risk was 2.52 (95% 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 preexisting 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=243-2.75, P<0.0001).
Conclusions—Antipsychotic use may be associated with a transient increase in risk for AMI, possibly mediated by dopamine type 3 receptor blockades. Further education on drug safety and research into the underlying biological mechanisms is needed.
- Received January 12, 2014.
- Revision received May 5, 2014.
- Accepted May 8, 2014.