Citation

Moore N, Lagnaoui R, Begaud B. Therapie 1999; 54(2): e285.

Copyright

(Copyright © 1999, John Libbey Eurotext)

DOI

unavailable

PMID

unavailable

Abstract

Sertindule has been suspended from the market because of suspected excess risk of cardiovascular mortality, presumably related to QT prolongation, as with other neuroleptics. To assess possible risk factors, we reanalysed pooled data from clinical trials, relating deaths with age, sex. dose and duration of treatment previous medical history, QTc values pre-treatment, after titration, and at last known value, and with plasma scrtindole and metabolite concentrations. In addition, we obtained data concerning deaths during clinical trials with risperidone and olanzapine.

RESULTS show that cardiac deaths during clinical trials were related to age. previous medical history (cardiovascular, endocrine and metabolic), but not with pre or post-treatment QTc. or with scrtindole concentrations. Sertindole increased QTc by a mean of 20 msec, with a significant relationship with plasma concentrations. Risk of death overall was 1.9 per 100 patient-years {PY), of cardiac death 0.8 per 100 PY. These values are those expected for a population of schizophrenic patients. Compared to olanzapine and risperidone, the overall death rate was identical. The risk of suicide was lower with sertindole than risperidone and olanzapine, the risk of cardiac death higher. However, mean duration of follow-up was longer. When the risk of death was corrected for duration of follow-up (hazard function), there was no difference between sertindole and olanzapine. We did not demonstrate a higher risk of cardiac death with sertindole than with olanzapine or risperidone, and these deaths did not seem related to QT prolongation, but to background risk of cardiovascular disease in patients that are often heavy smokers, diabetic or obese.

Language: en