1. Risk of Serious Cardiac Events in Older Adults Using Antipsychotic Agents Sandhya Mehta, MS; Hua Chen, MD, PhD; Michael Johnson, PhD; and Rajender R. Aparasu, MPharm, PhD Am J Geriatr Pharmacother. 2011; 9: 120-132 Alicia Williams 2012 PharmD Candidate Mercer University COPHS July 7, 2011

2. Typical Antipsychotics loxapine fluphenazine triflupromazine chlorprothixene haloperidol chlorpromazine thioridazine prochlorperazine promazine trifluperazine thiothexene molindone perphenazine acetophenazine mesoridazine paliperidone pimozide perphenazine-amitriptyline

3. Atypical Antipsychotics clozapine olanzapine risperidone quetiapine ziprasidone aripiprazole

4. Background Antipsychotic agents can cause cardiovascular events through multiple mechanisms: prolongation of the QT interval causes orthostasis and tachyarrhythmias Torsade de pointes raised lupus anticoagulant and anticardiolipin antibody levels can lead to increased risk of venous thromboembolism increased occurrence of metabolic syndrome such as type 2 diabetes, weight gain, and hypertriglyceridemia

5. Background

9. Objective To compare the risk of serious cardiac events in older adults taking typical antipsychotics with those taking atypical antipsychotics

10. Study Design A propensity-matched retrospective cohort study was conducted. The base population included all older adults aged ≥50 years old who were on antipsychotics from July 1, 2000 to December 31, 2007. No funding was received for this study.

11. Inclusion/Exclusion Criteria Participants must have been continuously eligible 6 months before and 6 months after the index date Index date: Antipsychotic initiation The first prescription fill date of antipsychotic medication after at least 6 months without a prescription fill date for these medications The minimum follow-up period was 6 months after the index date. maximum: 1 year

12. Patient Demographics A total of 5580 patients were selected in each antipsychotic users group after propensity score matching.

13. Intervention Prescription and medication information were derived from the IMS LifeLink Health Plan Claims database. The two groups were matched on a propensity score to minimize the baseline differences between the groups. Survival analysis was conducted on the matched cohort to assess the risk of serious cardiovascular events between the two groups.

14. Primary Endpoint Hospitalizations or emergency room visit due to serious cardiac events, including: thromboembolism, myocardial infarction, cardiac arrest, ventricular arrhythmias, within one year after the index date

15. Results Serious cardiac events were found in: 666 (11.9%) of atypical antipsychotic users 698 (12.4%) of typical antipsychotic users Survival analysis revealed that typical antipsychotic users were at increased risk of serious cardiovascular events hazard ratio = 1.21; 95% CI, 1.04-1.40

16. Conclusion Moderate increases in risk of serious cardiac events are associated with older adults using typical antipsychotic agents compared with atypical users. There is a strong need to assess the benefit- to-risk ratio of antipsychotics before prescribing them to a vulnerable population such as the elderly.

17. Comment The use of computer-recorded information to capture data did not allow them to ascertain whether the participants actually used their dispensed medications. The population referred to in the study comprised of community-dwelling older adults, and the results may not be generalizable to other settings.

18. Level of Evidence

19. Questions