Is the "interaction" between Clopidogrel and Omeprazole clinically relevant - yes I know the warnings but what does it actually mean to an individual?
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- Answered 16 Jun 2019 Conflict of interest declaration: None It’s difficult, from the literature, to be particularly certain! A 2015 paper “Clinical relevance of clopidogrel-proton pump inhibitors interaction”  reports: “Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination.” A small 2018 study , in health volunteers, concluded: “These data do not demonstrate a significant interaction between common individual PPIs and clopidogrel in healthy volunteers who respond to clopidogrel alone. This adds data to a growing body of evidence indicating that the addition of a PPI may have a weak effect on clopidogrel's antiplatelet properties, and may only be relevant in specific clinical circumstances.” A systematic review looked at outcomes for patients after PCI  and they found, in the population studied: “The combined use of clopidogrel with PPIs is still associated with significantly higher adverse cardiovascular events such as MACEs, ST and MI following PCI supporting results of the previously published meta-analysis. However, long-term mortality is not statistically significant warranting further analysis with randomized patients.” Finally, in 2012 the UK Medicine’s Information looked at this  and reported the following: “There have been no randomised trials to date which have been specifically designed to assess the effect of PPIs on clinical outcomes in patients taking clopidogrel. Secondary analyses of the COGENT, TRITON-TIMI 38 and PLATO trials have not shown an increased risk of major adverse cardiovascular events in patients taking PPIs and clopidogrel together. Treatment decisions regarding concomitant use of clopidogrel and PPIs must balance the overall risks and benefits and consider the risk of cardiovascular and gastrointestinal complications in individual patients. In some patients the benefits of PPI may outweigh the risk of reduced clopidogrel efficacy. Separate guidance produced by the AAC/ACG/AHA and ESC suggests that there is not enough evidence for a clinically meaningful interaction and that PPIs should not be withheld in patients on clopidogrel if they are clinically needed.” References 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419089/ 2. https://www.sciencedirect.com/science/article/abs/pii/S1052305718300168 3. https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-016-0453-6 4. https://www.surreyandsussex.nhs.uk/wp-content/uploads/2013/04/UKMi-PPIs-Clopidogrel-Interaction.pdf