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

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.