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Clopidogrel interactions not clear cut

The implications of the research published in the Canadian Medical Association Journal on clopidogrel are not necessarily as clear as they seem.

The paper shows a 1.27-fold increased risk of readmission for those currently on clopidogrel and a PPI, but no raised risk when it is taken with pantoprazole.

The premise that PPIs affect clopidogrel is not new, though the clinical significance has not up until now been established.

The assumption is that PPIs affect the cytochrome P450 system, but pantoprazole, according to the paper, does not.

But there is literature saying the opposite.

A paper in Clinical Pharmacology and Therapeutics concluded: 'These results indicate the stereoselective metabolism of pantoprazole depends on S-mephenytoin 4'-hydroxylase (CYP2C19).' There is therefore some confusion over the theoretical advantage of pantoprazole.

It is known that reflux affects ST segments of the ECG, possibly through tachykinin release, and we could propose that current use of PPIs correlates with reflux.

But this alternative explanation for the apparent interaction between clopidogrel and PPIs loses strength if pantoprazole is innocent and there is a good theoretical basis for this innocence.

Until the pantoprazole issue is clarified, we must be cautious about drawing conclusions from this trial.

It is concerning that a statement is made in the paper relating to pantoprazole and the cytochrome system that is in direct contradiction to data provided elsewhere.

From Dr Mark Christopher Aley, Chandler's Ford, Hampshire

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