Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review
Evidence Based Medicine
Focks JJ et al. – Despite indications of reduced antiplatelet activity ex vivo in the case of proton pump inhibitors (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.Methods
- PubMed, Web–of–Science, Cochrane Database and reference lists of related articles.
- 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.
- Two investigators independently reviewed the identified articles for eligibility, and one author extracted the data.
- 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.