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.
Authors
- Sarah Hardoon (ORCID: https://orcid.org/0000-0002-3044-3713)
- K All- Man
- Naomi Launders (ORCID: https://orcid.org/0000-0003-4241-938X)
- D Osborn
- Neil M Davies (ORCID: https://orcid.org/0000-0002-2460-0508)
- Joseph Hayes (ORCID: https://orcid.org/0000-0003-2286-3862)
- Alvin Richards-Belle
- Elvira Bramon
Institutions
- University College London Hospitals NHS Foundation Trust (GB)
- Universities UK (GB)
- Norwegian University of Science and Technology (NO)
- North East London NHS Foundation Trust (GB)
- University College London (GB)
- University of Hong Kong (HK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-21
- DOI
- https://doi.org/10.1038/s41467-025-67843-w
- Primary Topic
- Schizophrenia research and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Mental Health Research UK
- Wellcome Trust
- Health and Care Research Wales
- Scottish Government
- UK Research and Innovation
- Cancer Research UK
- National Institute for Health and Care Research
- British Heart Foundation
- Department of Health and Social Care
- British Medical Association
- University College London
- European Commission
- Public Health Agency
- Innovation and Technology Commission
- Norges Forskningsråd
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Health and Social Care Research and Development Division