Antipsychotic medications and the risk of major adverse cardiovascular events in patients with schizophrenia

Background

Antipsychotic medications are associated with metabolic adverse effects that constitute established risk factors for major adverse cardiovascular events (myocardial infarction or stroke, MACE), yet evidence regarding the association between antipsychotic treatment and cardiovascular risk remains equivocal. This question is particularly relevant in patients with schizophrenia, who have a high burden of cardiovascular morbidity and mortality. In addition, patients receiving antipsychotic treatment may differ from untreated patients in their contact with healthcare services and monitoring of cardiovascular risk factors. This study assesses the association between antipsychotic medication use and the risk of MACE in a large population-based cohort of patients with schizophrenia, with follow-up of up to 18 years.

Aims

To assess the association between antipsychotic exposure and major adverse cardiovascular events in a population-based cohort of patients with schizophrenia spectrum disorders, and to examine associations by duration, cumulative dose and medication group.

Methods

This retrospective cohort study used administrative data from Clalit Health Services, Israel’s largest health maintenance organization. Patients with schizophrenia spectrum disorders were identified using ICD-10 codes F20–F28. Major adverse cardiovascular events were defined as first acute myocardial infarction or stroke. Follow-up extended from 1 January 2006 to first event or 31 December 2023. Among 75,435 eligible patients, 9,025 who experienced a major adverse cardiovascular event were matched 1:2 to 18,050 controls using propensity score nearest-neighbor matching. Antipsychotic exposure was derived from pharmacy dispensing records and modelled as cumulative years, treatment for one year or more versus no treatment, duration categories, cumulative defined daily doses and medication group. Quetiapine, olanzapine and clozapine were grouped as antipsychotics with higher metabolic liability. Conditional logistic regression estimated odds ratios and 95% confidence intervals, adjusted for chronic obstructive pulmonary disease, obesity, hypertension, diabetes mellitus and dyslipidemia.

Results

In the matched cohort, antipsychotic use was lower among cases than controls (52.6% versus 62.6%). COPD (odds ratio 1.208, 95% confidence interval 1.128–1.294, p<0.001), hypertension (2.256, 2.097–2.428, p<0.001), diabetes mellitus (1.372, 1.287–1.462, p<0.001) and dyslipidemia (3.867, 3.639–4.110, p<0.001) were associated with higher odds of major adverse cardiovascular events; obesity was not significant (1.018, 0.959–1.082, p=0.553). Each additional year of antipsychotic treatment was associated with lower adjusted odds of major adverse cardiovascular events (0.955, 0.947–0.963, p<0.001). Treatment for one year or more was associated with lower adjusted odds compared with no treatment (0.560, 0.522–0.602, p<0.001). This association was consistent across duration and cumulative defined daily dose categories. Lower adjusted odds were observed for quetiapine, olanzapine and clozapine (0.579, 0.496–0.675, p<0.001) and for other antipsychotics (0.654, 0.612–0.699, p<0.001).

Conclusions

Long-term antipsychotic treatment was associated with lower odds of myocardial infarction or stroke in patients with schizophrenia spectrum disorders. This finding was consistent across dose, duration and medication groups. As residual confounding, confounding by indication and differences in health care engagement may contribute, the results should not be interpreted as evidence of a direct cardioprotective drug effect. The findings support continued antipsychotic treatment when clinically indicated, alongside cardiovascular risk monitoring.

References

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