CMAJ • March 31, 2009; 180 (7). First published January 28, 2009; doi:10.1503/cmaj.082001
© 2009 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

David N. Juurlink, MD PhD, Tara Gomes, MHSc, Dennis T. Ko, MD MSc, Paul E. Szmitko, MD, Peter C. Austin, PhD, Jack V. Tu, MD PhD, David A. Henry, MD, Alex Kopp, BA and Muhammad M. Mamdani, PharmD MPH

From the Department of Medicine (Juurlink, Ko, Tu), Sunnybrook Health Sciences Centre, Toronto, Ont.; the Institute for Clinical Evaluative Sciences (Juurlink, Gomes, Ko, Austin, Tu, Henry, Kopp, Mamdani), Toronto, Ont.; the Department of Medicine (Szmitko, Mamdani), St. Michael's Hospital, Toronto, Ont.; and the Department of Medicine (Juurlink, Ko, Tu, Henry, Mamdani), the Department of Health Policy, Management and Evaluation (Austin, Henry) and the Dalla Lana School of Public Health (Austin), University of Toronto, Toronto, Ont.


Figure 118
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  		Figure 1: Study design. The solid black line indicates the period following hospital discharge after treatment of acute myocardial infarction. We excluded patients who did not receive a prescription for clopidogrel within 3 days of the discharge date (upward arrow). Among the remaining patients, cases were those readmitted because of myocardial infarction within 90 days after discharge. We attempted to identify 3 matched controls, with no myocardial infarction before the same date (the index date, indicated by downward arrow) for each case. Use of proton pump inhibitors before the index date was categorized as current (within 30 days), previous (31–90 days) or remote (91–180 days).

 

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  		Table 1.

 

Figure 218
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  		Figure 2: Association between acid-reducing therapies and adverse outcomes. Current use of proton pump inhibitors (within 30 days before the index date) was associated with recurrent infarction within 90 days and 1 year following hospital discharge after treatment of acute myocardial infarction (MI) among patients who were receiving clopidogrel. No such association was apparent with earlier therapy or among patients who were not receiving clopidogrel following acute MI. Treatment with histamine H2-receptor antagonists or pantoprazole, neither of which inhibits cytochrome P450 2C19, was not associated with recurrent infarction, whereas treatment with other proton pump inhibitors (omeprazole, lansoprazole and rabeprazole) was associated with reinfarction. Risk of death was not increased during therapy with proton pump inhibitors. *Data are for current proton pump inhibitor use unless stated otherwise.

 

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  		Table 2.