Do PPIs cancel Clopidogrel benefits?

A Canadian based population study looked at patients who had an MI, were given Clopidogrel +/- a PPI. They found giving a PPI (omeprazole, lansoperazole, rabeprazole ) that inhibits Cytochrome p450 2C19 is associated with a OR of 1.4 of a recurrent MI in the first 30 days following an MI. Pantoprazole did not have this association and is the single PPI that does not inhibit CYP 450 2C19. This effect was not noted with H2 antagonists.

Clopidogrel is a pro-drug converted to its active form by the enzyme CYP 450 2C19. This enzyme which sits inside hepatic cells in the mitochondira and the endoplasmic reticulum busily adds an extra oxygen to the molecules its processes. The interesting thing is according to the wikipedia entry 15-20% of Asians have poor CYP 450 2C19 activity! So will it change my practice? Probably early days yet, populations studies are open to errors, everyone will call for a RCT (especially the companies that make PPIs), and pantoprazole is a sensible choce at least for the first 30 days while we try and work out whether this study is replicated by others. The other important question is: are 15-20% of Asians with poor CYP 450 2C19 activity benefiting from Clopidogrel?

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