CNS Drugs

, Volume 28, Issue 10, pp 963–973 | Cite as

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

  • Björn Pasternak
  • Henrik Svanström
  • Mattis F. Ranthe
  • Mads Melbye
  • Anders Hviid
Original Research Article



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.


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.


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.


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.



BP, HS, MFR, MM, and AH contributed to the conception and design of the study, the analysis and interpretation of the study results, and critically revised the manuscript. BP drafted the manuscript. HS acquired the data and conducted the statistical analyses. AH and MM supervised the study. BP, HS, MFR, MM, and AH approved the final version of the manuscript for submission.


The Danish Health and Medicines Authority funded the study. The funding body had no role in the study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication. All authors are independent from the funding agency. The views and conclusions expressed in this paper are those of the authors, and may not be understood or quoted as being made on behalf of or reflecting the position of the Danish Health and Medicines Authority.

Conflicts of interest

BP, HS, MFR, MM, and AH have no conflicts of interest.

Supplementary material

40263_2014_176_MOESM1_ESM.pdf (55 kb)
Supplementary material 1 (PDF 55 kb)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Björn Pasternak
    • 1
  • Henrik Svanström
    • 1
  • Mattis F. Ranthe
    • 1
  • Mads Melbye
    • 1
    • 2
  • Anders Hviid
    • 1
  1. 1.Department of Epidemiology ResearchStatens Serum InstitutCopenhagen SDenmark
  2. 2.Department of MedicineStanford School of MedicineStanfordUSA

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