Antipsychotic Drugs and Risks of Myocardial Infarction: A Self-Controlled Case Series Study

Study Questions:

What is the association between antipsychotics and myocardial infarction (MI) using the self-controlled case series design that eliminates between-person confounding effects?

Methods:

All the patients with a first recorded MI and prescription for an antipsychotic identified in the Clinical Practice Research Datalink linked to the Myocardial Ischemia National Audit Project were selected for the self-controlled case series. The incidence ratio of MI during risk periods following the initiation of antipsychotic use relative to unexposed periods was estimated within individuals. A classical case-control study was undertaken for comparative purposes comparing antipsychotic exposure among cases and matched controls.

Results:

The authors identified 1,546 exposed cases for the self-controlled case series and found evidence of an association during the first 30 days after the first prescription of an antipsychotic, for first-generation agents (incidence rate ratio [IRR], 2.82; 95% confidence interval [CI], 2.0-3.99) and second-generation agents (IRR, 2.5; 95% CI, 1.18-5.32). Similar results were found for the case-control study for new users of first- (odds ratio [OR], 3.19; 95% CI, 1.9-5.37) and second-generation agents (OR, 2.55; 95% CI, 0.93-7.01) within 30 days of their MI.

Conclusions:

The authors concluded that there was an increased risk of MI in the period following the initiation of antipsychotics that was not attributable to differences between people prescribed and not prescribed antipsychotics.

Perspective:

This study reports that new users of antipsychotics were at an increased risk of MI during the first month of drug use. The increased risks were similar among those with and without diagnosed dementia or prior cardiovascular disease. As antipsychotics are an effective intervention for some major psychiatric conditions, the relatively small increased absolute risk of MI is unlikely to alter their benefit–risk balance when used appropriately. However, when used in unlicensed indications without proven efficacy, such as dementia, the balance of risks and benefits is likely to be less favorable, and risk of MI needs to be seriously considered.


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