Adverse cardiac events in out‐patients initiating clozapine treatment: a nationwide register‐based study

Objective Using national Danish registers, we estimated rates of clozapine‐associated cardiac adverse events. Rates of undiagnosed myocarditis were estimated by exploring causes of death after clozapine initiation. Method Through nationwide health registers, we identified all out‐patients initiating antipsychotic treatment (January 1, 1996–January 1, 2015). Rates of clozapine‐associated myocarditis and pericarditis within 2 months from clozapine initiation and rates of cardiomyopathy within 1–2 years from clozapine initiation were compared to rates for other antipsychotics. Mortality within 2 months from clozapine initiation was extracted. Results Three thousand two hundred and sixty‐two patients of a total 7932 patients initiated clozapine as out‐patients (41.12%). One patient (0.03%) developed myocarditis, and no patients developed pericarditis within 2 months from clozapine initiation. Two (0.06%) and four patients (0.12%) developed cardiomyopathy within 1 and 2 years respectively. Rates were similar for other antipsychotics. Twenty‐six patients died within 2 months from clozapine initiation. Pneumonia (23.08%) and stroke (11.54%) were the main causes of death. We estimated the maximum rate of clozapine‐associated fatal myocarditis to 0.28%. Conclusion Cardiac adverse effects in Danish out‐patients initiating clozapine treatment are extremely rare and these rates appear to be comparable to those observed for other antipsychotic drugs.