A retrospective analysis of cardiovascular outcomes of clozapine treated individuals within Hunter New England

BACKGROUND: Clozapine has demonstrated superiority in improving both positive and negative symptoms of treatment-resistant schizophrenia; however, there are associated treatment-limiting side effects, including myocarditis, cardiomyopathy and agranulocytosis. AIM: This retrospective cohort study describes the prevalence of myocarditis, left ventricular (LV) dysfunction, cardiovascular risk factors and outcomes in a cohort of patients maintained on clozapine therapy. METHODS: Data were retrospectively collated from patients who had a diagnosis of schizophrenia, had been managed with clozapine at any stage during their care and undergone at least one echocardiogram. RESULTS: Between March 2020 and September 2021 674 patients were identified, 71% were male, with a mean age of 47 years old (interquartile range (IQR) 40-57). The mean duration of clozapine use was 7 years (IQR 4-13). The overall mortality was 5.54% during the follow-up period. Myocarditis was identified in one patient (0.15%) within the first 30 days, and an additional five cases were identified over the follow-up period (0.89%). The combined incidence of heart failure (HF) and myocarditis was 1.6% during the follow-up period. There was no association between LV size and function at baseline or during follow-up and adverse cardiac outcomes (comprising death, myocarditis, HF). Older age at initiation of therapy and baseline E/e' ratio were associated with risk of HF and myocarditis. CONCLUSION: The overall incidence of myocarditis and HF during follow-up was low, with surveillance echocardiography offering limited predictive value. Patients maintained on clozapine are at risk of significant cardiovascular sequelae, likely reflecting an adverse risk factor profile.