Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials

Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database

“…5) A number of recent commentaries from experts have argued that there is no evidence that this potential drug interaction has any clinical impact. 4,5,9,10,[32][33][34] The ACCF/ACG/AHA 2010 Expert Consensus Document is neutral with respect to a clinical interaction between PPIs and clopidogrel, citing the benefit/risk balance between the overall cardiovascular benefit and gastrointestinal complications. 1) Our study suggests that the combined administration of clopidogrel and aspirin with PPIs has little influence on the reporting of embolic/thrombotic events (Table 7), which supports the Expert Consensus Document guidelines.…”

“…8) In contrast, a number of observational studies and commentaries showed no interaction between clopidogrel and PPIs. 5,9,10) Significant controversy exists regarding cardiovascular adverse events that could arise from a drug interaction between clopidogrel and PPIs. Given the conflicting data, the optimal dosing for patients who require concomitant therapy with clopidogrel and PPIs is unknown.…”

Current Oral Antiplatelets: Focus Update on Prasugrel

“…In a single-center, open-label, randomized study, Small et al 23 concluded that concurrent use of lansoprazole and prasugrel did not decrease the inhibition of platelet aggregation by prasugrel, whereas lansoprazole lowered the level of inhibition of platelet aggregation when used concurrently with clopidogrel. Interestingly, an analysis of 2 randomized trials by O'Donoghue et al 24 showed that, when clinically indicated, PPIs can be used in patients taking either clopidogrel or prasugrel. Hence, conflicting evidence of the safety of the concurrent use of clopidogrel and PPIs still exists, but all available evidence about the concurrent use of prasugrel and PPIs points toward relative safety.…”

PPIs and Clopidogrel: The Band Plays On…………

“…Furthermore, where particular outcomes are infrequent, observational studies may be FUNCTIONAL GI DISORDERS ucm191169.htm ), van Boxel et al found no diff erence in apparent cardiovascular risk among the PPIs they examined -including those discouraged by the FDA. Others have similarly found no apparent diff erence among the various PPIs with respect to rates of cardiovascular events in clopidogrel users ( 3,7 ). Th erefore, a patient who requires PPI co-therapy should be prescribed the agent that he or she fi nds most accessible and aff ordable.…”

“…If one were to sample the published literature indiscriminately, one might conclude that PPI co-therapy led to worse cardiovascular outcomes among patients receiving clopidogrel ( 1,2 ). Alternatively, one might conclude that PPI co-therapy had no deleterious infl uence on cardiovascular outcomes, and that it also produced appreciable benefi ts such as a reduction in all-cause mortality ( 3 ) or at least in adverse gastrointestinal outcomes ( http://www.the heart.org/article/1007145.do ). Th at is why it is so important to have reliable and careful analyses of these apparently confl icting data, such as those by Laine and Hennekens recently published in this journal ( 4 ).…”