Clozapine-treated patients and myocardial infarction in adults: a pharmacovigilance study in VigiBase interpreted in the context of the literature

Clozapine is the best treatment for treatment-resistant schizophrenia (TRS) but is associated with metabolic adverse drug reactions (ADRs). The international pharmacovigilance database (VigiBase) uses the information component (IC) as a disproportionality analysis. On 1 July 2024, we studied in VigiBase: 1) the myocardial infarction (MI) ICs for antipsychotics and 2) clozapine reports for MI since clozapine’s introduction. After excluding 298 patients with incomplete data, 1490 adults were studied for fatal outcomes using logistic regression with adjusted odds ratios (aOR) and survival analysis. Clozapine was associated with the highest IC (IC = 0.903; IC₀₂₅ = 0.835). Olanzapine (IC = 0.524; IC₀₂₅ = 0.398) showed a lower but significant association. The ICs for quetiapine, risperidone and haloperidol were non-significant or negative. Mortality in 1490 adult clozapine-treated patients with MI was 68%. Using a baseline age 18–44 years, age 45–64 years had a significant (<i>p</i> &lt; 0.001) aOR = 1.87 with CI 1.43–2.44, while age ≥65 years had a significant (<i>p</i> &lt; 0.001) aOR = 4.07 with CI 2.77–5.97. High clozapine doses (&gt;600 mg/day) displayed an aOR = 2.18 for fatal outcomes. A MI IC around 0.9 is higher than that of other antipsychotics, but we cannot rule out that it is explained by TRS present in clozapine-treated patients.