title: Prevalence of cardiovascular and metabolic events in patients prescribed clozapine: a retrospective observational, clinical cohort study.
abstract: BACKGROUND
  The efficacy of clozapine for the treatment of schizophrenia has been demonstrated. However, a range of adverse events have been associated with its use. To date, there remains a paucity of data regarding the prevalence of clozapine-induced cardiovascular (CV) and parameters associated with the development of metabolic syndrome, alongside associated risk factors for their development.
  
  
  METHODS
  An observational, clinical cohort study design of 355 clozapine patients who were enrolled in the Barwon Health Clozapine Program at Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were accessed retrospectively. Multivariate logistic regression was used to determine associations with adverse event(s).
  
  
  RESULTS
  Older age of commencement with clozapine was consistently associated with increased risk of CV abnormalities, with the exception of tachycardia where older age was protective (Odds Ratio [OR]: 0.97; 95% Confidence Intervals [CI]: 0.95, 0.99). Males had significantly greater odds of most metabolic disturbances with the exception of being obese (BMI: ≥30 OR: 0.45; 95% CIs: 0.24, 0.85). Older age of commencement was a significantly associated variable with High- Density Lipoprotein-cholesterol (OR: 1.03; 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04; 95% CIs: 1.02, 1.07). An increase in BMI was consistently and significantly associated with all metabolic events.
  
  
  CONCLUSIONS
  Male patients who are obese at any point during treatment and older at treatment commencement may be the most vulnerable to adverse CV and metabolic events. While future studies using a matched case-control design may be required to verify these findings, we recommend that treating clinicians consider these risks when assessing patient suitability to clozapine therapy.
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Kitchener House, Geelong Hospital, Ryrie St, Geelong, Victoria, 3220, Australia. nhyde@barwonhealth.org.au.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hyde
authors.forename: Seetal
authors.initials: S
authors.lastname: Dodd
authors.forename: Kamalesh
authors.initials: K
authors.lastname: Venugopal
authors.forename: Christa
authors.initials: C
authors.lastname: Purdie
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Adrienne
authors.initials: A
authors.lastname: O'Neil
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D008076:Cholesterol, HDL / Q000097:blood; D003024:Clozapine / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000150:complications; D014739:Victoria / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D003024:Clozapine