Progress Report - May 2009

Paper accepted for publication

An article describing the study case definition and characterising the features of the first 38 cases with reference to control patients who took clozapine continuously without developing cardiac problems has been accepted by the Journal of Clinical Psychiatry.  We expect it to be published towards the end of this year.

Fatal cases

Of 75 confirmed cases, we have now documented 9 fatal cases, occurring 1996 to 2006 with reasonably even scatter across the years. Six occurred after publication of the pivotal article by Kilian et al documenting Australian cases of myocarditis (Lancet November 1999).

A feature of each of the cases is that apparently no one had any notion before the patient died that they had myocarditis. Two (possibly 3) had no prodrome of clinical illness.  Time from start of clozapine to death was 14-34 (mean 21) days

Monitoring for myocarditis

The current monitoring guidelines for myocarditis in patients starting clozapine do not recommend active monitoring beyond Day 14.  The time to onset for cases included in this study so far is 10-33 days, with a predominance of cases developing between days 14 and 21.  Stopping monitoring at Day 14 means that unless another trigger for checking cardiac function is present, most cases will be missed.

We are planning to prepare a paper proposing monitoring guidelines based on the evidence we have collected in this study.

The Table below shows the level of compliance with the current guidelines among the controls.  These controls started clozapine 1996-2008.  Some started before the guidelines were available (December 1999). 

Of 20 control patients who started clozapine between 1 January 2006 and 31 December 2008, 4 had no troponin check during the first 35 days of clozapine, despite a baseline value being obtained, and 3 had only one troponin check.  In this recent sample, troponin monitoring failed to meet the inadequate requirements of the current guidelines in 35% of patients.

Table: Troponin monitoring during the first 35 days of clozapine treatment among 93 control patients without myocarditis