Clopidogrel and proton pump inhibitors--where do we stand in 2012?

Hdl Handle:
http://hdl.handle.net/10147/253649
Title:
Clopidogrel and proton pump inhibitors--where do we stand in 2012?
Authors:
Drepper, Michael D; Spahr, Laurent; Frossard, Jean Louis
Affiliation:
Division of Gastroenterology, Department of Internal Medicine, Geneva University Hospital, 14 Geneva CH-1211, Switzerland.
Citation:
Clopidogrel and proton pump inhibitors--where do we stand in 2012? 2012, 18 (18):2161-71 World J. Gastroenterol.
Publisher:
World journal of gastroenterology : WJG
Journal:
World journal of gastroenterology : WJG
Issue Date:
14-May-2012
URI:
http://hdl.handle.net/10147/253649
DOI:
10.3748/wjg.v18.i18.2161
PubMed ID:
22611308
Abstract:
Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.
Item Type:
Article
Language:
en
MeSH:
Animals; Aryl Hydrocarbon Hydroxylases; Aspirin; Biotransformation; Cardiovascular Diseases; Drug Interactions; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Ticlopidine
ISSN:
1007-9327

Full metadata record

DC FieldValue Language
dc.contributor.authorDrepper, Michael Den_GB
dc.contributor.authorSpahr, Laurenten_GB
dc.contributor.authorFrossard, Jean Louisen_GB
dc.date.accessioned2012-11-28T12:25:30Z-
dc.date.available2012-11-28T12:25:30Z-
dc.date.issued2012-05-14-
dc.identifier.citationClopidogrel and proton pump inhibitors--where do we stand in 2012? 2012, 18 (18):2161-71 World J. Gastroenterol.en_GB
dc.identifier.issn1007-9327-
dc.identifier.pmid22611308-
dc.identifier.doi10.3748/wjg.v18.i18.2161-
dc.identifier.urihttp://hdl.handle.net/10147/253649-
dc.description.abstractClopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.en_GB
dc.language.isoenen
dc.publisherWorld journal of gastroenterology : WJGen_GB
dc.rightsArchived with thanks to World journal of gastroenterology : WJGen_GB
dc.subject.meshAnimals-
dc.subject.meshAryl Hydrocarbon Hydroxylases-
dc.subject.meshAspirin-
dc.subject.meshBiotransformation-
dc.subject.meshCardiovascular Diseases-
dc.subject.meshDrug Interactions-
dc.subject.meshDrug Therapy, Combination-
dc.subject.meshGastrointestinal Hemorrhage-
dc.subject.meshHumans-
dc.subject.meshPlatelet Aggregation Inhibitors-
dc.subject.meshProton Pump Inhibitors-
dc.subject.meshRisk Assessment-
dc.subject.meshRisk Factors-
dc.subject.meshTiclopidine-
dc.titleClopidogrel and proton pump inhibitors--where do we stand in 2012?en_GB
dc.typeArticleen
dc.contributor.departmentDivision of Gastroenterology, Department of Internal Medicine, Geneva University Hospital, 14 Geneva CH-1211, Switzerland.en_GB
dc.identifier.journalWorld journal of gastroenterology : WJGen_GB
dc.description.provinceLeinsteren
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