Cardiovascular Disease Mortality in Patients With Chronic Schizophrenia Treated With Clozapine

Abstract

Background Cardiovascular disease (CVD) mortality in schizophrenia is more frequent than in the general population. Whether second generation antipsychotics (SGAs) increase risk of CVD morbidity and mortality has yet to be determined. Methods Using an administrative database, we identified schizophrenia patients, treated in Maryland, who started clozapine (n=1084) or never treated with clozapine (initiated on risperidone)(n=602) between 1994 and 2000. Deaths between 1994 and 2004 were identified by the Social Security Death Index and death records were obtained. Results During the 6–10 year followup period there were 136 deaths of which 43 were CVD. CVD mortality in patients < 55 years old at medication start was approximately 1.1% (cloz: 1.1%, risp: 1.0%) in both groups at five years, and 2.7% (clozapine) and 2.8% (risperidone) at ten years (χ2=0.12, df=1, p=0.73). Patients started ≥ 55 years had CVD mortality of 8.5% (clozapine) and 3.6% (risperidone) at five years and 16.0%(clozapine) and 5.7% (risperidone) at ten years (χ2 =2.13, df=1, p=0.144). In a Cox regression model, patients with age ≥55 years were at greater risk of mortality than younger patients (HR=4.6, p<0.001); whites were at greater risk than non-whites (HR=2.1, p=0.046); however, SGA treatment (HR=1.2, 95% CI 0.6 to 2.4, p=0.61) and sex (HR=0.9, p=0.69), were not statistically significant predictors of CVD; nor was there a significant age x clozapine interaction (χ2=1.52, df=1, p=0.22). Age-, race-, and gender adjusted Standardized Mortality Ratios (SMR) were significantly elevated (clozapine 4.70, 95%CI=3.19–6.67; risperidone 2.88, 95%CI=1.38–5.30) compared to year 2000 rates for the Maryland general population but did not differ by antipsychotic group (Π2=1.42, df=1, p=0.23). Conclusions The risk of CVD mortality in schizophrenia does not differ between clozapine and risperidone in adults despite known differences in risk profiles for weight gain and metabolic side effects. However, we cannot rule out an increased risk of CV mortality among those starting treatment at age ≥ 55 years.

Mortality in schizophrenia

“…In fact, Kelly et al (2010) themselves had noted that 'Given the relatively limited number of older patients in our sample, we cannot rule out that in older people, clozapine may have a more detrimental effect on cardiovascular mortality than risperidone'. They selectively reviewed the findings from Tiihonen et al (2009) without stating that the study has drawn criticism for these findings despite citing that publication (De Hert et al, 2010) in a different context.…”

“…They made a point that the study by Dean and Thuras (2009) (a study that has several methodological limitations) found typical antipsychotics 'had numerically greater association with cardiovascular mortality' than atypical antipsychotics (rates of 1178 and 519 per 100,000/year, significance not stated). However, they did not report that in the study by Dean and Thuras (2009) heart disease related mortality was lowest (475 per 100,000/year) among those patients who had used both typical and atypical antipsychotic medications.The authors failed to note that in the study by Kelly et al (2010) there was a nonsignificant trend of higher cardiovascular disease (CVD) mortality with clozapine than risperidone with increasing duration of exposure for patients started on clozapine at age55 years (8.5% for clozapine and 3.6% for risperidone at 5 years and 16.0% for clozapine and 5.7% for risperidone at 10 years). In fact, Kelly et al (2010) themselves had noted that 'Given the relatively limited number of older patients in our sample, we cannot rule out that in older people, clozapine may have a more detrimental effect on cardiovascular mortality than risperidone'.…”

Psychiatric aspects of chronic physical disease

“…30 Cardiac causes of death are seen in more than 40% of patients with schizophrenia who are smokers, and standardized mortality ratios for cardiovascular death are about three times greater in people with schizophrenia than the general population. 31 However, diagnosis and treatment of co-morbid medical complications lag behind and much comorbidity goes untreated. A similar picture exists for the psychiatric complications of chronic physical disorder.…”

Association between antipsychotics and cardiovascular adverse events: A systematic review

“…Duplication of scientific articles, which also had inadequate control groups, were eliminated. 13,14 In all, three articles (articles 1, 15 …”