Potential interaction between proton pump inhibitor and clopidogrel
Abstract
Clopidogrel is an anti-platelet agent commonly used in patients with atherosclerotic cardiovascular (CV) disease. Although formerly considered safe, several studies reported that the use of clopidogrel may cause a significant increase in the rate of gastrointestinal (GI) bleeding. This adverse effect could be minimized by coadministration of proton pump inhibitor (PPI). However, since PPI and clopidogrel share the same metabolic pathway, it has been hypothesized that the administration of PPI following clopidogrel therapy may cause a reduction in its anti-platelet effect, thereby increasing the risk of CV events. Recent studies found no significant inhibition in the activation of clopidogrel by CYP2C19 with administration of PPI in vitro. Pharmacokinetic and pharmacodynamic studies, as well as clinical studies, reported conflicting results regarding the potential interaction between PPI and clopidogrel. Until now, the available study investigated the PPI-clopidogrel interaction are primarily observational. The COGENT study is the only prospective, placebo-controlled trial examined the PPI-clopidogrel interaction. This study revealed no significant increase in CV events in patients receiving PPI following clopidogrel therapy, compared to the control group. Though remains controversial, current expert consensus recommended the administration of PPI in patients receiving clopidogrel, particularly in high-risk patients. (Med J Indones. 2013;22:57-62)
Keywords: Cardiovascular, clopidogrel, gastrointestinal, proton pump inhibitor
References
Laine L, Hennekens C. Proton pump inhibitor and clopidogrel interaction: fact or fiction? Am J Gastroenterol. 2010;105:34-9.
Madanick RD. Proton pump inhibitor side effects and drug interactions: much ado about nothing? Cleveland Clinical Journal of Medicine. 2011;78:39-45.
Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909-17.
Depta JP, Bhatt DL. Omeprazole and clopidogrel: should clinicians be worried? Cleveland Clinical Journal of Medicine. 2010;77:113-5.
Cryer BL. Reducing the risks of gastrointestinal bleeding with antiplatelet therapies. N Engl J Med. 2005;352:287-9.
Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. New Engl J Med. 2005;352:238-44.
Vallurupalli NG, Goldhaber SZ. Gastrointestinal complications of dual antiplatelet therapy. Circulation. 2006;113:e655-8.
Ng FH, Wong SY, Lau YK, et al. Upper gastrointestinal bleeding during anti-platelet therapy. The Hong Kong Medical Diary. 2008;13:27-9.
Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American college of cardiology foundation task force on clinical expert consensus documents. Circulation. 2008;118:1894-909.
Horn JR, Hansten PD. Clopidogrel-proton pump inhibitor interaction: an update. Pharmacy Times. 2010;02:47.
Abraham NS, Hlatky MA, Antman EL, et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American college of cardiology foundation task force on clinical expert consensus documents. Circulation. 2010;122:2619-33.
Zhang H, Ragueneau-Majlessi, Levy RH. Interaction between clopidogrel and proton pump inhibitors: hypothesis to explain multifactorial CYP2C19 inhibition. Drug Metabolism Letters. 2009;3:287-9.
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. JACC. 2008;51:256-60.
Hulot JS, Collet JP, Silvain J, et al. Cardiovascular Risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. JACC. 2010;56:135-42.
Shuldiner AR, Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849-57.
Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354-62.
Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther. 2010;31:810-23.
Lima JP, Brophy JM. Conflicting evidence: whatâs a clinician to do? Ann Intern Med. 2010;153:413-5.
Copyright (c) 2013 Indra Kurniawan, Marcellus Simadibrata
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.
