Response to Letter by Tho

Article Outline

• References
• Copyright

We thank Dr Tho and colleagues for their interest regarding our recent article.¹ As proposed by the authors, we have tested the assumption whether the concomitant use of proton pump inhibitors (PPIs) and lipophilic statins reduces the antiplatelet effect of clopidogrel (n = 364). All patients in our study were on clopidogrel treatment. There was no difference in the platelet reactivity index in patients receiving concomitant PPI and lipophilic statin (atorvastatin, simvastatin, or fluvastatin) compared with patients without any of these drugs (median 51%, interquartile range [IQ] 34%-63%, vs 51%, IQ 31%-65%; P = .68). The platelet reactivity index was in the same range in patients on pantoprazole and lipophilic statin (48%, IQ 32%-65%), esomeprazole and lipophilic statin (56%, IQ 35%-65%), lipophilic statin without PPI (48%, IQ 24%-65%), pantoprazole without statin (54%, IQ 36%-73%), or esomeprazole without statin (51%, IQ 25%-69%; P = .26). Similarly, the concomitant PPI and statin treatment did not reduce the antiplatelet effect of clopidogrel as assessed by impedance aggregometry. The adenosine diphosphate–induced platelet aggregation in patients on both PPI and lipophilic statin as well as in patients without either drug class was similar (36 U, IQ 19-58, vs 29 U, IQ 14-60 U; P = .37). The adenosine diphosphate–induced platelet aggregation was in the same range in patients on pantoprazole and lipophilic statin (35 U, IQ 18-57 U), esomeprazole and lipophilic statin (43 U, IQ 22-63 U), lipophilic statin without PPI (29 U, IQ 17-50 U), pantoprazole without statin (44 U, IQ 20-75 U), or esomeprazole without statin (32 U, IQ 16-55 U; P = .34).

Data are controversial whether PPIs alter the antiplatelet effect of clopidogrel. Three retrospective analyses have shown that patients on concomitant PPI treatment have an increased risk of adverse clinical outcomes,², ³, ⁴ whereas the subgroup analysis of the CREDO trial could not confirm these results.⁵ Two studies indicate that clopidogrel-PPI drug-drug interaction might not be a class effect: a case-control study, which has reported that concomitant treatment with PPIs other than pantoprazole increased the risk of reinfarction,⁶ and our study, which has shown that pantoprazole and esomeprazole had no influence on the antiplatelet effect of clopidogrel.¹

Back to Article Outline

References 

1. Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009;157:148.e1–148.e5
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (181 KB)
   • CrossRef
2. Pezalla E, Day D, Pulliadath I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol. 2008;52:1038–1039
   • View In Article
   • Full Text
   • Full-Text PDF (47 KB)
   • CrossRef
3. 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
   • View In Article
   • CrossRef
4. Aubert R, Epstein R, Teagarden J, et al. Proton pump inhibitors effect on clopidogrel effectiveness: the Clopidogrel Medco Outcomes Study. Circulation. 2008;118:S815
   • View In Article
5. Dunn SP, Macaulay TE, Brennan DM, et al. Baseline proton pump inhibitor use is associated with increased cardiovascular events with and without the use of clopidogrel in the CREDO trial. Circulation. 2008;118:S815
   • View In Article
6. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;
   • View In Article