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Original Research

Incidence of Cardiovascular Outcomes and Diabetes Mellitus Among Users of Second-Generation Antipsychotics

Leslie Citrome, MD, MPH; Jenna M. Collins, MPH; Beth L. Nordstrom, PhD, MPH; Edward J. Rosen, BS; Ross Baker, PhD, MBA; Anagha Nadkarni, PhD; and Iftekhar Kalsekar, PhD

Published: December 15, 2013

Article Abstract

Objective: To examine the risk of cardiovascular outcomes and diabetes mellitus in patients prescribed second-generation antipsychotics.

Method: From the MarketScan claims database, nondiabetic adults prescribed aripiprazole between July 2003 and March 2010 were propensity score-matched with patients prescribed olanzapine, quetiapine, risperidone, and ziprasidone. Patients were followed through the claims for International Classification of Diseases, Ninth Revision codes indicating myocardial infarction, stroke, heart failure, coronary bypass/angioplasty procedures, and incident diabetes. Incidence rates of each outcome were calculated and compared between aripiprazole and the other second-generation antipsychotics using Cox models.

Results: Aripiprazole initiators were matched 1:1 to 9,917 olanzapine, 14,935 quetiapine, 10,192 risperidone, and 5,696 ziprasidone initiators. Increased risk was found with olanzapine for stroke (hazard ratio = 1.43; 95% confidence interval, 1.05-1.95) and any cardiovascular event (1.28; 1.05-1.55); with quetiapine for stroke (1.58; 1.19-2.09), heart failure (1.55; 1.15-2.11), and any cardiovascular event (1.50; 1.25-1.79); and with risperidone for stroke (1.54; 1.12-2.12), heart failure (1.43; 1.02-1.99), and any cardiovascular event (1.49; 1.21-1.83). Ziprasidone showed no significant difference in risk from aripiprazole for any outcome. Incidence of diabetes ranged from 18 to 21 events per 1,000 person-years in each cohort and did not differ significantly between second-generation drugs.

Conclusions: This analysis of real-world data found lower risk of some cardiovascular events with aripiprazole than with olanzapine, quetiapine, or risperidone, but no differences were found with ziprasidone. There were no significant differences in risk of diabetes. Limitations include use of claims data and inability to adequately control for differential prescribing of second-generation antipsychotics to patients at higher risk of diabetes.

J Clin Psychiatry 2013;74(12):1199-1206

Submitted: June 13, 2013; accepted October 9, 2013 (doi:10.4088/JCP.13m08642).

Corresponding author: Leslie Citrome, MD, MPH, 11 Medical Park Dr, Ste 106, Pomona, NY 10970 (

Volume: 74

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