title: Cardiovascular disease mortality in patients with chronic schizophrenia treated with clozapine: a retrospective cohort study.
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
  We conducted a retrospective cohort study using an administrative database to identify patients with DSM-III- or DSM-IV-diagnosed schizophrenia, treated in Maryland, who started clozapine treatment (n = 1,084) or were 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- to 10-year follow-up period, there were 136 deaths, of which 43 were attributed to CVD. Cardiovascular disease mortality in patients aged younger than 55 years at medication start was approximately 1.1% (clozapine, 1.1%; risperidone, 1.0%) in both groups at 5 years and 2.7% (clozapine) and 2.8% (risperidone) at 10 years (chi(2)(1) = 0.12, P = .73). Patients who started treatment at ages >or= 55 years had CVD mortality of 8.5% (clozapine) and 3.6% (risperidone) at 5 years and 16.0% (clozapine) and 5.7% (risperidone) at 10 years (chi(2)(1) = 2.13, P = .144). In a Cox regression model, patients aged >or= 55 years were at greater risk of mortality than younger patients (hazard ratio = 4.6, P < .001); whites were at greater risk than nonwhites (HR = 2.1, P = .046); however, SGA treatment (HR = 1.2; 95% CI, 0.6-2.4; P = .61) and sex (HR = 0.9, P = .69) were not statistically significant predictors of CVD, nor was there a significant age x clozapine interaction (chi(2)(1) = 1.52, P = .22). Age-, race-, and gender-adjusted standardized mortality ratios 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 (chi(2)(1) = 1.42, P = .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 CVD mortality among those starting treatment at ages 55 years or older.
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Box 21247, Baltimore, MD 21228, USA. dkelly@mprc.umaryland.edu
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kelly
authors.forename: Robert P
authors.initials: RP
authors.lastname: McMahon
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Love
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Wehring
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Shim
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Warren
authors.forename: Robert R
authors.initials: RR
authors.lastname: Conley
mesh_terms: D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality*; D002908:Chronic Disease; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D015995:Prevalence; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D014481:United States / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine