# Risk of major adverse cardiovascular events with aripiprazole versus olanzapine, quetiapine, and risperidone in severe mental illness: a target trial emulation

## TL;DR

This study compares the risk of major cardiovascular events among patients with severe mental illness starting different antipsychotics, finding similar long-term risks but higher risk with continued risperidone use.

## Contribution

The study provides real-world evidence comparing cardiovascular risks of aripiprazole versus other antipsychotics in patients with severe mental illness.

## Key findings

- Patients initiating aripiprazole had similar five-year MACE risk as those starting olanzapine, quetiapine, and risperidone.
- Continued use of risperidone was associated with higher MACE risk compared to aripiprazole.
- Antipsychotic selection does not significantly impact long-term cardiovascular event risk for most patients.

## Abstract

Initiating aripiprazole as antipsychotic monotherapy rather than olanzapine, quetiapine, or risperidone, might prevent/delay major adverse cardiovascular events (MACEs) over the long-term in people diagnosed with severe mental illness. Using Clinical Practice Research Datalink data, we emulated a trial of aripiprazole versus olanzapine, quetiapine, and risperidone in 20,404 patients 2005–2014. Primary outcome was five-year MACE risk (composite of hospitalisation for acute myocardial infarction or stroke and cardiovascular death). Here we show that patients initiating aripiprazole had a similar five-year MACE risk as those initiating olanzapine (risk ratio: 1.03, 95% CI, 0.78-1.32), quetiapine (1.02, 95% CI, 0.72-1.32), and risperidone (0.88, 95% CI, 0.67-1.17). Risk was lower among patients initiating and continuing aripiprazole versus risperidone (0.58, 95% CI, 0.39-0.84). For patients at clinical equipoise, antipsychotic selection does not appear to significantly impact risk of the most severe, long-term cardiovascular events. However, further research is needed to replicate our finding of increased risk with continued risperidone use versus aripiprazole.

Initiating aripiprazole antipsychotic monotherapy versus olanzapine, quetiapine or risperidone might reduce cardiovascular event risk in severe mental illness. Here, the authors show patients initiating aripiprazole had similar 5-year risk as the comparators, but risk was higher in those continuing risperidone versus aripiprazole