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Warnings Without Guidance: Patient Responses to an FDA Warning About Ezetimibe

Shrank, William H. MD, MSHS*,†; Choudhry, Niteesh K. MD, PhD*; Tong, Angela MS; Myers, Jessica PhD; Fischer, Michael A. MD, MPH*; Swanton, Kellie BA; Slezak, Julie MPH; Brennan, Troyen A. MD, JD; Liberman, Joshua N. PhD; Moffit, Susan MPP, PhD§; Avorn, Jerry MD*; Carpenter, Daniel PhD

doi: 10.1097/MLR.0b013e31825517b6
Original Articles

Background: In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication.

Methods: Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication.

Results: Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (P<0.0001). Younger patients, those who lived in low-income zip codes, and female patients were less likely to discontinue therapy (P<0.0001 for all). Among nonpersistent patients, rates of clinically appropriate switching increased from 10.8% before to 16.5% after the FDA warning (P=0.004).

Conclusions: A substantial increase in ezetimibe nonpersistence rates was seen after an FDA communication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.

*Department of Medicine, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston

Center for American Political Studies, Faculty of Arts and Sciences, Harvard University, Cambridge, MA

CVS Caremark, Woonsocket

§Department of Political Science, Taubman Center for Public Policy, Brown University, Providence, RI

Supported by a research grant from CVS Caremark. W.H.S. is supported by a career development award from the National Heart, Lung and Blood Institute (HL-090505).

J.S., and T.B. are employees of CVS Caremark, a company whose profits are related to medication choices. J.L. was an employee of CVS Caremark at the time of this work and is now an employee of Geisinger Healthcare. The authors from Brigham and Women’s Hospital, Harvard Medical School and Harvard University have received research funding from CVS Caremark, Express Scripts and Aetna, companies whose profits are related to medication choices.

Each of the authors had full access to all of the data in this study and contributed to the writing of this manuscript.

Reprints: William H. Shrank, MD, MSHS, Department of Medicine, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.