CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Martine Gilard, MD*,
Jean-Christophe Cornily, MD and
Jacques Boschat, MD
* Département de Cardiologie, CHU de la Cavale Blanche, Boulevard Tanguy Prigent, 29609 Brest Cedex, France (Email: Martine.gilard{at}chu-brest.fr).
We thank Dr. Pezalla and colleagues for their interest in our article (1). We are highly interested in the strong link reported between proton pump inhibitor (PPI) use and clinical coronary artery adverse events in patients under clopidogrel therapy, according to their medical and pharmacy databases.
Our study showed that omeprazole significantly decreased the clopidogrel inhibitory effect on platelet P2Y12 as assessed by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation test. This study has opened the way to a clinical validation of this concept. A first step was reached by a report from another French team showing a sensitivity of 100% of the VASP test in predicting major adverse cardiac events (MACE) (2). Moreover, Bonello et al. (3) showed that adjusting the clopidogrel loading dose according to the VASP index, before PCI, in daily clinical practice improved the clinical outcome after coronary stenting.
Data reported in the letter by Dr. Pezalla and colleagues tend to confirm that adding PPI to an antiplatelet therapy with clopidogrel increases MACE.
A strong link seems to exist between clopidogrel–PPI interaction, VASP index, and clinical outcomes. However, some questions remain. Are all PPIs equal? When co-prescription of clopidogrel and PPI is mandatory, what is the best attitude? A VASP test may be performed and clopidogrel dose may be adjusted to obtain a VASP index higher than 50% (4–6). According to Bonello et al. (3), an additional bolus dose of clopidogrel may decrease clinical events, but how long should high doses be maintained?
Additional randomized trials with clinical end points must be performed. Nevertheless, biological data from our randomized double-blind trial, confirmed by clinical results of registries such as the one reported in the letter by Dr. Pezalla and colleagues, should lead us to avoid systematic addition of PPI when clopidogrel is prescribed.
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References
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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]2. Bonello L, Paganelli F, Arpin-Bornet M, et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events J Thromb Haemost 2007;5:1630-1636.[CrossRef][Web of Science][Medline] 3. Bonello L, Camoin-Jau L, Arques S, et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study J Am Coll Cardiol 2008;51:1404-1411.[Abstract/Free Full Text] 4. Schumacher WA, Bostwick JS, Ogletree ML, et al. Biomarker optimization to track the antithrombotic and hemostatic effects of clopidogrel in rats J Pharmacol Exp Ther 2007;322:369-377.[Abstract/Free Full Text] 5. Blindt B, Stellbrink K, de Taeye A, et al. The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis Thromb Haemost 2007;98:1329-1334.[Web of Science][Medline] 6. Barragan P, Bouvier JL, Roquebert PO, et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation Catheter Cardiovasc Interv 2003;59:295-302.[CrossRef][Web of Science][Medline]
Related Article
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Initial Assessment of Clinical Impact of a Drug Interaction Between Clopidogrel and Proton Pump Inhibitors
- Edmund Pezalla, David Day, and Indira Pulliadath
J. Am. Coll. Cardiol. 2008 52: 1038-1039.
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