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The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?

The potential interaction between clopidogrel and proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) raises serious concerns for cardiologists. However, in patients on this combination of drugs, there is no conclusive evidence of an increase in adverse cardiovascular events....

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Autores principales: Sharma, Rakesh K, Reddy, Hanumanth K, Sharma, Rohit K, Moazazi, Mathilde, Elango, Lovett, Singh, Vibhuti N, Williams, D Keith, Voelker, Donald J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262372/
https://www.ncbi.nlm.nih.gov/pubmed/22291500
http://dx.doi.org/10.2147/CPAA.S9807
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author Sharma, Rakesh K
Reddy, Hanumanth K
Sharma, Rohit K
Moazazi, Mathilde
Elango, Lovett
Singh, Vibhuti N
Williams, D Keith
Voelker, Donald J
author_facet Sharma, Rakesh K
Reddy, Hanumanth K
Sharma, Rohit K
Moazazi, Mathilde
Elango, Lovett
Singh, Vibhuti N
Williams, D Keith
Voelker, Donald J
author_sort Sharma, Rakesh K
collection PubMed
description The potential interaction between clopidogrel and proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) raises serious concerns for cardiologists. However, in patients on this combination of drugs, there is no conclusive evidence of an increase in adverse cardiovascular events. From pharmacologic and pharmacodynamic perspectives, there is a real interaction between clopidogrel and PPIs because of the competitive inhibition of CYP2C19 isoenzyme which is required for biotransformation of clopidogrel to its active metabolite. The consequent decrease in the availability of this active metabolite leads to attenuation of antiplatelet efficacy of clopidogrel. In several observational trials, it was shown that decreased antiplatelet effect of clopidogrel due to PPIs may translate into poor cardiovascular outcomes. However, an incomplete RCT (COGENT) and a post hoc analysis of two large trials (PRINCIPLE-TIMI 44 and TRITON-TIMI 38 trial) showed no significant adverse cardiovascular events with this combination. Caution is however needed in patients who are hypometabolizers of clopidogrel putting them at a higher risk of adverse coronary events. Since 3% of patients are likely to be hypometabolizers of clopidogrel, routine combination of clopidogrel and PPIs should be avoided. There is a heightened awareness of this interaction following multiple advisory warnings. At the same time, one should not withhold PPIs in patients who are at a high risk of developing gastrointestinal (GI) bleeding. In these patients, selected choices of PPI such as pantoprazole may be helpful and for low risk patients, serious consideration should be given to H(2) receptor antagonists or antacids. Therefore, while not compromising the cardioprotective effect of antiplatelet agents, the gastroprotective benefit of PPI should be strongly considered in patients who need both. Health care providers should remain alert to more outcome data. Future researchers will need to demonstrate the safety of coadministration of PPIs and clopidogrel and trials should be powered to detect major adverse cardiovascular events and facilitate risk stratification based on genetic polymorphism.
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spelling pubmed-32623722012-01-30 The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance? Sharma, Rakesh K Reddy, Hanumanth K Sharma, Rohit K Moazazi, Mathilde Elango, Lovett Singh, Vibhuti N Williams, D Keith Voelker, Donald J Clin Pharmacol Review The potential interaction between clopidogrel and proton pump inhibitors (PPI) in patients with acute coronary syndrome (ACS) raises serious concerns for cardiologists. However, in patients on this combination of drugs, there is no conclusive evidence of an increase in adverse cardiovascular events. From pharmacologic and pharmacodynamic perspectives, there is a real interaction between clopidogrel and PPIs because of the competitive inhibition of CYP2C19 isoenzyme which is required for biotransformation of clopidogrel to its active metabolite. The consequent decrease in the availability of this active metabolite leads to attenuation of antiplatelet efficacy of clopidogrel. In several observational trials, it was shown that decreased antiplatelet effect of clopidogrel due to PPIs may translate into poor cardiovascular outcomes. However, an incomplete RCT (COGENT) and a post hoc analysis of two large trials (PRINCIPLE-TIMI 44 and TRITON-TIMI 38 trial) showed no significant adverse cardiovascular events with this combination. Caution is however needed in patients who are hypometabolizers of clopidogrel putting them at a higher risk of adverse coronary events. Since 3% of patients are likely to be hypometabolizers of clopidogrel, routine combination of clopidogrel and PPIs should be avoided. There is a heightened awareness of this interaction following multiple advisory warnings. At the same time, one should not withhold PPIs in patients who are at a high risk of developing gastrointestinal (GI) bleeding. In these patients, selected choices of PPI such as pantoprazole may be helpful and for low risk patients, serious consideration should be given to H(2) receptor antagonists or antacids. Therefore, while not compromising the cardioprotective effect of antiplatelet agents, the gastroprotective benefit of PPI should be strongly considered in patients who need both. Health care providers should remain alert to more outcome data. Future researchers will need to demonstrate the safety of coadministration of PPIs and clopidogrel and trials should be powered to detect major adverse cardiovascular events and facilitate risk stratification based on genetic polymorphism. Dove Medical Press 2010-09-06 /pmc/articles/PMC3262372/ /pubmed/22291500 http://dx.doi.org/10.2147/CPAA.S9807 Text en © 2010 Sharma et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Sharma, Rakesh K
Reddy, Hanumanth K
Sharma, Rohit K
Moazazi, Mathilde
Elango, Lovett
Singh, Vibhuti N
Williams, D Keith
Voelker, Donald J
The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?
title The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?
title_full The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?
title_fullStr The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?
title_full_unstemmed The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?
title_short The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?
title_sort interaction between clopidogrel and proton pump inhibitors (ppi): is there any clinical relevance?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262372/
https://www.ncbi.nlm.nih.gov/pubmed/22291500
http://dx.doi.org/10.2147/CPAA.S9807
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