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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

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,

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Page 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,

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 Williams2012 PharmD CandidateMercer University COPHS

July 7, 2011

Page 2: 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,

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

Page 3: 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,

Atypical Antipsychotics

clozapine olanzapine risperidone quetiapine ziprasidone aripiprazole

Page 4: 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,

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

Page 5: 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,

Background

Page 6: 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,

Background

Page 7: 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,

Background

Page 8: 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,

Background

Page 9: 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,

Objective

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

Page 10: 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,

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.

Page 11: 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,

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

Page 12: 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,

Patient Demographics

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

Page 13: 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,

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.

Page 14: 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,

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

Page 15: 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,

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

Page 16: 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,

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.

Page 17: 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,

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.

Page 18: 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,

Level of Evidence

Page 19: 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,

Questions