Ethnic differences in antipsychotic effects on HDL

 Evidence from the US CATIE Schizophrenia Study suggests that there may be underlying racial differences in how antipsychotic treatment influences high density lipoprotein (HDL) cholesterol.  In this trial, white subjects who took perphenzaine and non-whites who took ziprasidone showed an increase in HDL cholesterol levels.  These findings may have implications for choice of medication in patients at high cardiometabolic risk.

 Daumit GL, Goff DC, Meyer JM et al. Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE schizophrenia study. Schizophrenia Res 2008;105:175-87.

 The CATIE (Clinical Antipsychotic Trial of Intervention Effectiveness) Schizophrenia Study was conducted between January 2001 and December 2004 at 57 sites in the US and included 1460 outpatients with schizophrenia (diagnosed by a research clinician using a modified SCID interview). Patients were randomly assigned to double-blind treatment with one of the second-generation antipsychotics - olanzapine, quetiapine or risperidone and ziprasidone – or the first generation antipsychotic perphenazine and were followed up for up to 18 months or until initial treatment discontinuation. Mean treatment duration was 9.5 months. The primary outcome of the study was the change from baseline in 10-year coronary heart disease (CHD) risk, estimated using the Framingham Heart Study formula.1  Secondary outcomes included changes in diabetes, smoking status, hypertension and total and HDL cholesterol by antipsychotic treatment.

 Overall, 1125 patients were included in the analysis of primary outcome at the end of phase 1. Baseline characteristics of these patients are summarised below.

 Baseline characteristics of the CATIE study population

·         Predominantly male (75%) and white (62%)

·         Mean age 40.7 years

·         Risk factors: 12% had diabetes, 58% smoked and 34% had hypertension

·         Mean HDL cholesterol 43.3 (± 13.4 mg/dL)

·         Baseline 10-year CHD risk: 8.1% to 9.1% across the treatment groups

 The authors found a significant difference (p=0.007) between the treatments in the mean change in 10-year CHD risk (adjusted for covariates which included baseline level of risk, time to treatment discontinuation and demographic and fasting baseline measures associated with change in CHD risk). The estimates of risk change were highest for olanzapine and lowest for risperidone and ziprasidone (Table 1).

 Table 1. Change in 10-year CHD risk estimates (mean ± SE) from baseline to end of phase 1, adjusted for covariates

 

Analysis of individual CHD risk factors showed no difference between the treatment groups for the change in smoking status, new-onset diabetes or hypertension. However, changes in total and HDL cholesterol at the end of phase 1 differed significantly between the groups. Across the groups, HDL cholesterol levels (adjusted for covariates) decreased in the olanzapine group (by 1.4 ± 0.5 mg/dL) and increased in the perphenazine (by 1.1 ± 0.6 mg/dL, p=0.001) and ziprasidone (by 1.9 ± 0.7 mg/dL, p<0.001) groups.

 Additionally, the authors identified an interaction between treatment and race for the change in HDL cholesterol. For white patients, HDL cholesterol was significantly increased in the perphenazine group (by 2.7 ± 0.7 mg/dL) compared with the olanzapine and quetiapine groups. However, for non-white subjects, an increase in HDL cholesterol was observed with ziprasidone (by 4.3 ± 1.4 mg/dL) compared with decreases for both olanzapine and perphenazine (Table 2).

 Table 2. Adjusted change in HDL cholesterol (mean ± SE) with each antipsychotic, overall and by race

 

The authors concluded that increases in HDL cholesterol (together with lowering in total cholesterol, data not shown here), were largely responsible for the difference in CHD risk between the treatments. ‘If replicated, identification of physiologic or molecular mechanisms underlying race differences in antipsychotic effects on HDL will be of considerable interest,’ concluded the authors.

 According to John Newcomer, Gregory B. Couch Professor of Psychiatry, Psychology and Medicine at Washington University School of Medicine, the study builds on growing evidence about the role of antipsychotics in what has been referred to as the ‘epidemic of cardiometabolic risk’ among severely mentally ill patients. ‘Given the U.S. Public Health Service focus on overweight and obesity as leading modifiable contributors to cardiovascular risk and diabetes risk, it is not surprising that there is growing interest in those medications – not just antipsychotics- that can significantly increase body weight or produce other effects that increase cardiometabolic risk,’ he said.

 While the data are intriguing, he also cautioned on the need for looking at prestudy treatment history in the CATIE population, to fully understand the results of this analysis. ‘It is less clear how much of the change in CHD risk is due to the intrinsic effects of the treatments or the effects of switching from whatever treatment subjects were on before,’ he commented.

 Reference

1. Wilson PW, D’Agostino RB, Levy D et al. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

  


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