Ethnic disparity in clozapine dosing and cardiotoxicity in New Zealand

To investigate ethnic disparities in the treatment and incidence of cardiotoxicity for patients prescribed clozapine in New Zealand.

A post hoc analysis was undertaken using data from four studies investigating clozapine cardiotoxicities in New Zealand: two population studies (one prospective, one retrospective) conducted in the Auckland District Health Board (2011-2017), and two studies of coronial autopsy records (2001-2016). The relationship between ethnicity and cases (N=26) of myocarditis and/or cardiomyopathy was examined in comparison to non-cases in the rest of the study population (N=161). Patient demographics, comorbidities, and risk factors were investigated for any associations with ethnicity, where data was available.

Māori and Pacific patients were over-represented in the population studies. Moreover, across the cohorts investigated 46% of myocarditis and cardiomyopathy cases were Māori. In contrast, only one case (4%) of cardiomyopathy was identified in a patient of Pacific descent. Where clozapine titration data was available, the rate of dose escalation was higher in Māori and Pacific peoples, as was the cumulative dose received before the first case of cardiotoxicity (day 13 of dose titration). Māori patients were more likely to be co-medicated with sodium valproate than others during clozapine titration, and sodium valproate was also significantly associated with myocarditis in these patients.

The factors underpinning the more rapid titration of Māori and Pacific patients onto clozapine and the increased use of concomitant sodium valproate in Māori are unclear. While the latter may explain the heightened risk of clozapine-induced myocarditis in Māori, further work is required to mitigate the effects of this inequity on the safe use of clozapine in New Zealand.