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Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a
Jeroen Jaspers Focks1, Marc A Brouwer, Martijn G H van Oijen
1Radboud University Nijmegen Medical Center, Department of Cardiology, Nijmegen, The Netherlands. j.jaspersfocks@gmail.com
Insights
Proton pump inhibitors (PPIs) may reduce clopidogrel's antiplatelet effect in lab studies, but clinical data remain controversial. Better designed studies show no substantiated adverse cardiovascular events with PPI use in clopidogrel patients.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Clopidogrel combined with aspirin improves outcomes in acute coronary syndromes.
- Laboratory studies suggest proton pump inhibitors (PPIs) may reduce clopidogrel's antiplatelet effect.
- Controversy exists regarding PPIs' impact on clopidogrel efficacy due to conflicting clinical data.
Purpose of the Study:
- To systematically review the impact of PPIs on platelet function and cardiovascular outcomes when used with clopidogrel.
Main Methods:
- Systematic review of studies from PubMed, Web-of-Science, and Cochrane Database.
- Inclusion of controlled studies on PPIs added to clopidogrel, including platelet function and clinical outcome studies.
- Data extraction by one author after independent review by two investigators.
Main Results:
- 70% of laboratory studies showed reduced platelet inhibition with PPIs and clopidogrel in healthy volunteers.
- 61% of studies in patients also indicated reduced platelet inhibition.
- Clinical studies (33) exhibited significant outcome heterogeneity (MACE risk ratios 0.64-4.58), with limited randomization and potential bias.
Conclusions:
- While ex vivo data suggest reduced antiplatelet activity, clinical consequences of PPIs with clopidogrel are controversial.
- Accumulating evidence from prospective studies does not substantiate an adverse clinical outcome from PPI use in clopidogrel patients.
- Conclusions from non-randomized data analyses may be unreliable.
Background:
Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel the controversy on this issue.
Purpose:
Systematic review of the impact of the addition of PPIs to clopidogrel on platelet function and cardiovascular outcome.
Data Sources:
PubMed, Web-of-Science, Cochrane Database and reference lists of related articles.
Study Selection:
Published articles on controlled studies addressing the addition of PPIs to clopidogrel. Platelet function studies describe patients as well as healthy volunteers. Clinical studies concern patients using clopidogrel for acute coronary syndromes or because of stent implantation for stable coronary disease.
Data Extraction:
Two investigators independently reviewed the identified articles for eligibility, and one author extracted the data.
Data Synthesis:
In 70% (7/10) of the laboratory studies examining healthy volunteers on clopidogrel, addition of PPIs resulted in a significant reduction in platelet inhibition. For patients, this was observed in 11/18 (61%) studies. The 33 clinical studies showed significant heterogeneity in observed outcomes, with risk ratios for major adverse cardiovascular events varying from 0.64 to 4.58 in the case of PPI use, which was randomly allocated in only two studies. Consequently, imbalances between prognosticators at baseline and PPI prescription bias markedly contributed to the variability in results.
Conclusions:
Despite indications of reduced antiplatelet activity ex vivo in the case of PPI administration in clopidogrel users, data on the clinical consequences are controversial. With the accumulating evidence from better designed, prospective clinical studies, an adverse effect of PPI use on clinical outcome in patients on clopidogrel cannot be substantiated. This review challenges the validity of conclusions based on quantitative analyses of predominantly non-randomised data.
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