Further information: Medical Treatment of Unstable Angina, Acute Non–ST-Elevation Myocardial Infarction, and Coronary Artery Spasm (see p937) and Percutaneous Coronary Intervention for Unstable Coronary Artery Disease (see p1005) from Cardiovascular Medicine, 3rd Edn*

In 2007, Eisenstein et al published “Clopidogrel Use and Long-Term Clinical Outcomes after Drug-Eluting Stent Implantation,” [1] in which the authors concluded that the use of clopidogrel reduced the risk of death or myocardial infarction (MI) in patients who had undergone percutaneous coronary intervention (PCI) and received a drug-eluting stent (DES). In addition to other studies on the use of antiplatelet therapy after PCI, the results of CURRENT-OASIS 7 should be available for presentation at the Scientific Sessions of the American Heart Association slated for November 14-17, 2009, and may define optimum dosing regimens for the use of clopidogrel. However, the use of clopidogrel in combination with a proton pump inhibitor has come under scrutiny, and at the Scientific Sessions of the American Heart Association held November 10–14, 2008, two studies [2,3] reported reduced effectiveness of clopidogrel when used in conjunction with a proton pump inhibitor. More recently, Ho et al [4] conducted a retrospective cohort study of 8205 acute coronary syndromes (ACS) patients after their discharge from 127 VA hospitals who were taking clopidogrel with or without a proton-pump inhibitor (PPI). Main outcome measures were all-cause mortality and/or rehospitalization for ACS. Of the 8205 total patients studied after discharge who were on clopidogrel, 5244 were also prescribed PPI while 2961 patients were not.

Death or hospitalization for ACS occurred in 1561 patients taking clopidogrel with PPI and in 615 patients taking only clopidogrel. Similar statistics from the paper showing adverse results when clopidogrel and PPI were used together were the result of multivariable analyses and a nested case-control study. In May 2009, the European Medicines Agency (EMEA) published an article titled, “Public statement on possible interaction between clopidogrel and proton pump inhibitors” [5]. The statement was written to reinforce the concerns as reported in studies, such as the aforementioned JAMA paper, suggesting the possibility of significant interactions that might occur between the combined use of clopidogrel and PPI that rendered clopidogrel less effective and placed patients at increased risk of thrombotic events, including MI. The resulting controversy seems to suggest that additional studies need to be conducted on the interaction between the combined use of clopidogrel and PPI in patients being treated for ACS

[1] Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 2007;297:159-168
[2] Aubert RE, Epstein RS, Teagarden JR, et al. Proton pump prohibitors effect on clopidogrel effectiveness: The medco outcomes study. Circulation 2008; 118(suppl 1):3998a
[3] Dunn SP, Macauley TE, Brennan DM, et al. Baseline proton pump inhibitor use is associated with increased cardiovascular events with and without use of clopidogrel in the CREDO trial. Circulation 2008; 118(suppl 1):3999a
[4] Ho M, 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
[5] Wathion N. European Medicines Agency. Public statement on possible interaction between clopidogrel and proton pump inhibitors. EMEA/328956/2009. May 2009 London

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