CORRESPONDENCE: LETTER TO THE EDITOR
Initial Assessment of Clinical Impact of a Drug Interaction Between Clopidogrel and Proton Pump Inhibitors
Edmund Pezalla, MD, MPH,
David Day, MS, RPh* and
Indira Pulliadath, MBA
* Aetna, Pharmacy Management, 151 Farmington Avenue, Hartford, Connecticut 06156 (Email: dayd{at}aetna.com).
After reading the article by Gilard et al. (1) regarding the influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin, we examined our medical and pharmacy databases for acute myocardial infarction (MI) rates in members receiving clopidogrel with or without concurrent proton pump inhibitor (PPI) therapy.
Our analysis included members younger than age 65 years who were determined to be adherent to clopidogrel therapy. Members were assigned to a no PPI exposure group (control), low PPI exposure group, or high PPI exposure group based on adherence rates to PPIs. Members were studied for a period of 1 year for claims with International Classification of Diseases-9th Revision diagnoses indicative of MI after starting clopidogrel therapy. We also examined comorbidities and severity of illness at the time of first clopidogrel use.
Our findings revealed 1-year acute MI rates of 1.38% (66 of 4,800 patients) in the control group, 3.08% (22 of 712 patients) in the low PPI exposure group, and 5.03% in the high PPI exposure group. Using the control group MI incidence as the expected MI rate, the difference in MI rates between the control and high exposure groups was significant (p < 0.05). Subsequent analysis identified small but significant comorbidity differences between the groups that could account for the findings. The high PPI exposure group had a slightly greater number of individuals with pre-existing hypertension, diabetes, and a slightly elevated overall severity of illness when clopidogrel was first prescribed.
To adjust for these differences, a subset of members was constructed within each group who all had diagnoses of ischemic heart disease, congestive heart failure, hypertension, hyperlipidemia, and diabetes before the start of clopidogrel therapy. Table 1
shows that differences in acute MI rates between the control and high PPI groups remained significant (p < 0.05) when these comorbidity differences were adjusted out of the analysis. Relative risk for acute MI in the high PPI exposure group was 337% greater than in the control group.
View this table:
[in this window]
[in a new window]
|
Table 1 Comparison of 1-Year Acute Myocardial Event Rates in Risk-Adjusted Members Receiving Clopidogrel With and Without Concomitant PPI Use
|
|
Although claims-based analyses are limited and cannot control for variables such as years of risk factor presence, weight gain, smoking history, and family history of coronary heart disease, we feel that evidence is pointing toward a potentially significant interaction between PPIs and clopidogrel that may decrease the ability of clopidogrel to prevent acute MI events.
 |
Footnotes
|
|---|
Please note: The authors of this letter are all employees of Aetna and received no external funding from any sources for this work.
|
References
|
|---|
1. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study J Am Coll Cardiol 2008;51:256-260.[Abstract/Free Full Text]
Related Article
-
Reply
- Martine Gilard, Jean-Christophe Cornily, and Jacques Boschat
J. Am. Coll. Cardiol. 2008 52: 1039.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
K. M. Stockl, L. Le, A. Zakharyan, A. S. M. Harada, B. K. Solow, J. E. Addiego, and S. Ramsey
Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor
Arch Intern Med,
April 26, 2010;
170(8):
704 - 710.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Verstuyft, T. Simon, and R. B. Kim
Personalized medicine and antiplatelet therapy: ready for prime time?
Eur. Heart J.,
August 2, 2009;
30(16):
1943 - 1963.
[Full Text]
[PDF]
|
|
|
|
Top
References