PLAVIX / PPI DRUG INTERACTION

I must begin this blog by saying that I am sadden at the sudden death of Dr Phillip Poole Wilson of the Imperial College of London on then 4th March 2009. Although I do not know Dr Wilson personally, I have attend many of his lectures. I find that he is very articulate, and a good teacher, and always being very balance in his views. He is obviously an expert in heart failure management, besides being a gentleman and teacher. We will all miss him and his contribution. My condolences to his family and loved ones.

Today, I intend to re-emphasize our concern of the Clopidogrel-proton Pump Inhibitor interactions. It is obvious that many of our CAD patients requiring drug-eluting stents, are often prescribed aspirin and clopidogrel ( standard dual anti-platelet therapy ). Of late, there have been many reports of clopidogrel-PPI interactions, that will attenuate the effects of clopidogrel. Could this be one of the causes of subacute stent thrombosis? We sometimes forget that clopidogrel is a pro-drug, and so requires CYP450 2C19 to activate. But CYP 450 2C19 is inhibited by most of the PPIs, except possibly pantozezole. As a result of this interaction, the effects of clopidogrel may be weakened. This is seen in up to 25% of the patients using clopidogrel and PPI. This was again emphasize in the latest paper by Dr Micheal Ho of Denver in the March 4th 2009. Dr Ho found that there was a 25% increase in cardiac deaths and re-hospitalisation in the patients taking the clopidogrel-PPI combination.
The exhortation is that when we start patients on dual anti-platelet therapy ( especially with aspirin ), we may have to resist the temptation of using PPI prophylactically. Otherwise we risk the higher risk of coronary thrombosis or stent thrombosis ( if stents have been used ). I understand that pantazezole, is less often used in Malaysia. Perhaps Wyeth ( now a division of Pfizer ) will consider marketing pantazezole, seeing that there is a particular niche use.
I also wish to highlight the fact that doctors and cardiologist may have to pay freater attention to drug metabolism and interactions in the pursuit of better care for their patients. Not enough is taught about the cytochrome CYP450 system, which is very important for drug metabolism.