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Published in: Digestive Diseases and Sciences 7/2010

01-07-2010 | Original Article

Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention

Authors: Ekta Gupta, Darpan Bansal, John Sotos, Kevin Olden

Published in: Digestive Diseases and Sciences | Issue 7/2010

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Abstract

Background

Recent studies have suggested that proton pump inhibitors (PPIs) attenuate the benefits of clopidogrel. The clinical relevance of this interaction in patients who have undergone percutaneous coronary intervention (PCI) is unknown. We hypothesized that post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used.

Aims

To determine whether post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used.

Methods

We reviewed the medical records of all the patients discharged on clopidogrel who underwent PCI from January 2003 to August 2004. The primary outcome studied was a major adverse cardiovascular event (MACE), which was defined as a composite of death, myocardial infarction, and target vessel failure.

Results

Of the 315 post-PCI patients who were discharged on clopidogrel, 72 were discharged on PPI. During a mean follow-up period of 50 months, patients discharged on concomitant clopidogrel-PPI therapy had a MACE rate of 56% (vs. 38% in the clopidogrel alone group) (P = 0.025) and had 95% excess risk of MACE.

Conclusion

Concomitant use of clopidogrel and PPI in post-PCI patients is associated with a higher risk of MACE. This suggests that PPIs may attenuate clopidogrel’s beneficial antiplatelet effect, which is crucial after PCI. Prospective randomized studies are warranted to provide definitive evidence for this interaction.
Literature
1.
go back to reference Steinhubl SR, Berger PB, Mann JT III, et al. CREDO Investigators. Clopidogrel for the reduction of events during observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411–2420.CrossRefPubMed Steinhubl SR, Berger PB, Mann JT III, et al. CREDO Investigators. Clopidogrel for the reduction of events during observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411–2420.CrossRefPubMed
2.
go back to reference Gurbel PA, Lau WC, Tantry US. Omeprazole: a possible new candidate influencing the antiplatelet effect of clopidogrel. J Am Coll Cardiol. 2008;51:261–263.CrossRefPubMed Gurbel PA, Lau WC, Tantry US. Omeprazole: a possible new candidate influencing the antiplatelet effect of clopidogrel. J Am Coll Cardiol. 2008;51:261–263.CrossRefPubMed
3.
go back to reference Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84:891–896.PubMed Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84:891–896.PubMed
4.
go back to reference Savi P, Herbert JM, Pflieger AM, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol. 1992;44:527–532.CrossRefPubMed Savi P, Herbert JM, Pflieger AM, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol. 1992;44:527–532.CrossRefPubMed
5.
go back to reference Kim KA, Park PW, Hong SJ, et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther. 2008;84:236–242.CrossRefPubMed Kim KA, Park PW, Hong SJ, et al. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther. 2008;84:236–242.CrossRefPubMed
6.
go back to reference Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. NEngl J Med. 2009;360:363–375.CrossRef Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. NEngl J Med. 2009;360:363–375.CrossRef
7.
go back to reference Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–362.CrossRefPubMed Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–362.CrossRefPubMed
8.
go back to reference Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301:937–944.CrossRefPubMed Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301:937–944.CrossRefPubMed
9.
go back to reference Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180:e1–e7. Epub CMAJ. 2009 Jan 28. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180:e1–e7. Epub CMAJ. 2009 Jan 28.
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009;157:148.e1–148.e5. Epub 2008 Nov 6.CrossRef Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009;157:148.e1–148.e5. Epub 2008 Nov 6.CrossRef
12.
go back to reference Li XQ, Andersson TB, Ahlstrom M, Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P-450 activities. Drug Metab Dispos. 2004;32:821–827.CrossRefPubMed Li XQ, Andersson TB, Ahlstrom M, Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P-450 activities. Drug Metab Dispos. 2004;32:821–827.CrossRefPubMed
Metadata
Title
Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention
Authors
Ekta Gupta
Darpan Bansal
John Sotos
Kevin Olden
Publication date
01-07-2010
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2010
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-0960-8

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