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Pantoprazole and rabeprazole would appear to be the least likely to inhibit 2C19, thereby potentially causing the least interference with clopidogrel activation. The clinical impact on this should be taken into consideration. Editor-in-Chief: Anthony J. Explanation It is now known that the proton pump inhibitor PPI class of medications can have a potential negative impact on the ability of clopidogrel to adequately inhibit platelet aggregation for the purposes of preventing stent thrombosis.
A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ ; The Clopidogrel Medco Outcomes Study. A national study of the effect of individual proton pump inhibitors on cardiovascular outcomes in patients treated with clopidogrel following coronary stenting: The Clopidogrel Outcomes Study. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA ; Abstract ; Baseline proton pump inhibitor use is associated with increased cardiovascular events with and without the use of clopidogrel in the CREDO trial.
Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. J Am Coll Cardiol ; Takeda Pharmaceuticals America, Inc. Deerfield, IL January AstraZeneca Pharmaceuticals LP. Wilmington, DE. Dig Dis Sci. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor.
Arch Intern Med. Relation of proton pump inhibitor use after percutaneous coronary intervention with drug-eluting stents to outcomes. Am J Cardiol. Recurrence of acute myocardial infarction in patients discharged on clopidogrel and a proton pump inhibitor after stent placement for acute myocardial infarction.
Clin Cardiol. United states Food and Drug Administration. European Medecines Agency. Accessed July 7, Clopidogrel with or without omeprazole in coronary artery disease. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med. Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study.
Clinical outcomes in patients with the concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention: an analysis from the Guthrie Health Off-Label Stent GHOST investigators. Circ Cardiovasc Interv. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome.
Effect of concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention. Proton pump inhibitors in patients treated with aspirin and clopidogrel after acute coronary syndrome. Rev Port Cardiol. The impact of treatment with omeprazole on the effectiveness of clopidogrel drug therapy during the first year after successful coronary stenting. Can J Cardiol. Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation.
Coron Artery Dis. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. The potential interaction between clopidogrel and proton pump inhibitors: a systematic review.
BMC Med. Identification of the human cytochrome P enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos. Cytochrome p polymorphisms and response to clopidogrel. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.
Genetic determinants of response to clopidogrel and cardiovascular events. Proton pump inhibitors, genetic polymorphisms and response to clopidogrel therapy. Thromb Haemost.
Br J Clin Pharmacol. Risk of adverse outcomes in Taiwan associated with concomitant use of clopidogrel and proton pump inhibitors in patients who received percutaneous coronary intervention. Clinical evidence of interaction between clopidogrel and proton pump inhibitors. World J Cardiol. Lettino M. Inhibition of the antithrombotic effects of clopidogrel by proton pump inhibitors: facts or fancies?
Eur J Intern Med. Clopidogrel and proton pump inhibitors: influence of pharmacological interactions on clinical outcomes and mechanistic explanations.
Shi S, Klotz U. Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol. Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet. Review article: the clinical pharmacology of proton pump inhibitors. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P activities.
Proton pump inhibitors: do differences in pharmacokinetics translate into differences in clinical outcomes? Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study.
Pharmacodynamic evaluation of pantoprazole therapy on clopidogrel effects: results of a prospective, randomized, crossover study. Adjusting effect estimates for unmeasured confounding with validation data using propensity score calibration. Am J Epidemiol. The bias due to incomplete matching. Indications for propensity scores and review of their use in pharmacoepidemiology.
Basic Clin Pharmacol Toxicol. Performance of propensity score calibration--a simulation study. Applying propensity scores estimated in a full cohort to adjust for confounding in subgroup analyses. Pharmacoepidemiol Drug Saf. The current warnings pertain only to omeprazole and esomeprazole the S-enantiomer of omeprazole and other inhibitors of CYP2C At this time, there is insufficient data to conclude that other proton pump inhibitors interact with clopidogrel.
These agents can be used as alternatives for acid reduction. Health care providers are highly encouraged to ask patients about over-the-counter medications because both omeprazole and cimetidine are available commercially without a prescription.
During the publication of this manuscript, two additional studies were published in the medical literature. The first was a retrospective cohort study using automated data from 20, patients hospitalized for myocardial infarction, coronary artery revascularization or unstable angina.
The second was an observational, retrospective study that included consecutive patients undergoing coronary stenting. Primary outcomes of cardiac death or nonfatal myocardial infarction were not significantly different in clopidogrel plus omeprazole group and in clopidogrel only group after 1 year.
Accessed on November 20, 2. J Am Coll Cardiology ; 3. CMAJ ; 4. JAMA ; 5. Lancet ; 6. J Am Coll Cardiol Jan 22;51 3 7. Circulation ; 8. Ann Intern Med ; 9.
On the other hand, the United States Food and Drug Administration and the European Medicines Agency revised the labelling of clopidogrel, which now mentions that omeprazole and esomeprazole should be avoided in patients treated with clopidogrel, that other acid-lowering agents with minimal or no inhibitory effects on CYP2C19 should be considered and that lansoprazole and pantoprazole have less inhibitory effect on the antiplatelet action of clopidogrel than omeprazole and esomeprazole[ 39 , 40 ].
In conclusion, even though pharmacodynamic studies suggest that omeprazole can attenuate the antiplatelet effect of clopidogrel, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Other PPIs also do not appear to interact with clopidogrel. Conflict-of-interest: We have no conflict of interest to declare. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers.
Peer-review started: January 15, First decision: March 6, Article in press: April 20, National Center for Biotechnology Information , U. World J Gastrointest Pharmacol Ther. Published online May 6. Stella D Bouziana and Konstantinos Tziomalos.
Author information Article notes Copyright and License information Disclaimer. Author contributions: Bouziana SD drafted the paper; Tziomalos K revised the draft critically for important intellectual content. Published by Baishideng Publishing Group Inc. All rights reserved. This article has been cited by other articles in PMC. Abstract Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke.
Table 1 Major observational studies that evaluated the effects of coadministration of clopidogrel and proton pump inhibitors on cardiovascular events. Population n Hazard ratio in patients who received clopidogrel and proton pump inhibitors vs patients treated with clopidogrel alone [10] Patients hospitalized for ACS or coronary revascularization 0.
Open in a separate window. Table 2 Polymorphisms that potentially affect the antiplatelet effect of clopidogrel. References 1. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients MATCH : randomised, double-blind, placebo-controlled trial.
Upper gastrointestinal bleeding in patients with acute coronary syndromes: clinical predictors and prophylactic role of proton pump inhibitors.
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