title: Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute major cardiovascular events in young and middle-aged adults: a nationwide register-based cohort study in Denmark.
abstract: BACKGROUND
  A number of serious cardiovascular safety concerns related to the use of atypical antipsychotics, compared with no use, have emerged, but nearly all reports are from studies of older patients. We aimed to compare the risk of cardiovascular events between the three most commonly used atypical antipsychotics in young and middle-aged adults.
  
  
  METHODS
  We conducted a nationwide register-based cohort study in Denmark, 1997-2011, including adults aged 18-64 years, who started treatment with oral or intramuscular olanzapine (n = 15,774), oral quetiapine (n = 18,717), and oral or intramuscular risperidone (n = 14,134). The primary outcome was any major cardiovascular event (composite of cardiovascular mortality, acute coronary syndrome, or ischemic stroke) within 1 year following treatment initiation. Cox regression was used to estimate hazard ratios (HRs) while on current antipsychotic monotherapy in the outpatient setting, adjusting for an outcome-specific disease risk score.
  
  
  RESULTS
  The crude rate of any major cardiovascular event was 5.3 per 1,000 person-years among olanzapine users, 3.4 in quetiapine users, and 5.2 in risperidone users. Compared with risperidone, the risk of any major cardiovascular event was not significantly different in olanzapine users (HR 0.90, 95 % confidence interval [CI] 0.53-1.52) and quetiapine users (HR 0.79, 95 % CI 0.45-1.39). The absolute risk difference per 1,000 person-years on treatment was -0.5 (95 % CI -2.4 to 2.7) events for olanzapine and -1.1 (95 % CI -2.9 to 2.0) events for quetiapine.
  
  
  CONCLUSIONS
  Among young and middle-aged outpatients, the risk of acute major cardiovascular events was similar with use of olanzapine, quetiapine, and risperidone. Although moderate relative differences cannot be ruled out, any differences are small in absolute terms.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark, bjp@ssi.dk.
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.forename: Mattis F
authors.initials: MF
authors.lastname: Ranthe
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003987:Dibenzothiazepines / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D016016:Proportional Hazards Models; D000069348:Quetiapine Fumarate; D012042:Registries; D012306:Risk; D018967:Risperidone / Q000009:adverse effects*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D018967:Risperidone; D000077152:Olanzapine