IPP et clopidogrel (7)

Theheart.org consacre un article à un papier et son éditorial, non encore publiés dans Circulation.

Le papier constate dans une population de 18565 patients extraits de 3 cohortes rétrospectives une augmentation non significative du critère combiné décès et infarctus du myocarde dans le groupe de patients prenant des IPP et du clopidogrel, par rapport au groupe uniquement sous clopidogrel.

L’éditorial, écrit par David N Juurlink (l’auteur du papier du CMAJ de mars 2009) résume très bien la situation, la met en perspective et propose une conduite à tenir aux cliniciens:

« 1. Evaluate the necessity of PPI therapy. Although PPIs are necessary for some patients, many others take the drugs for dubious indications. In these patients, treatment with a histamine H2 antagonist or antacid may suffice.

2. Consider using pantoprazole when a PPI is indicated. This suggestion stems from the observation that pantoprazole is less likely than omeprazole to inhibit CYP2C19,21 does not appear to attenuate the pharmacodynamic response to clopidogrel, and displayed no association with recurrent myocardial infarction in a large observational study of patients receiving clopidogrel. Other PPIs may also be relatively safe, but more data are needed. Lansoprazole is the most potent CYP2C19 inhibitor and is probably best avoided.

[NDLR: ce point est en contradiction avec la modification des RCP du clopidogrel qui déconseille la coprescription de ce dernier et de tous les IPP (pantoprazole compris), « sauf en cas de nécessité absolue ».]

3. Stagger the dosing of medications. This is perhaps the most important strategy and exploits the rapid metabolism of clopidogrel and the transient nature of PPI-mediated CYP2C19 inhibition. When dual therapy is necessary, taking a PPI at least 4 hours after clopidogrel should minimize the risk of interaction. »

Enfin, c’est une vision plutôt optimiste de l’éditorial, car en fait le doute persiste.

Il persiste d’autant plus que Juurlink revient carrément sur sa troisième proposition de conduite à tenir dans son entretien avec theheart.org:

« Juurlink said he has changed his stance somewhat on one particular issue following last week’s FDA alert. « In my editorial, I suggest—as have many others—that staggering of the doses of clopidogrel and PPIs would mitigate the effect of the interaction. » But he now maintains there are unpublished data that « I can’t speak to the source of, » to suggest that this approach is not correct. »

Il existe des données « cachées » qui sont en cours d’analyse, et qui vont sensiblement changer la donne dans les prochains mois:

« People sometimes have the reflex belief that the FDA are behind the curve, or that they are wrong. In this instance, they are not. I think we are going to see a lot more on this interaction in the next six to 12 months, and hear more from the FDA. They have a lot better handle on this than most people appreciate, » he said.

Donc, comme toujours dans cette histoire, wait and see there’s more to come.

°0°0°0°0°0°0°0°0°0°0°0°0°

Lisa Nainggolan. Keep clopidogrel/PPI interaction in perspective; expert predicts more to come from FDA. theheart.org. [Clinical Conditions > Clinical cardiology > Clinical cardiology]; Nov 26, 2009. Accessed at http://www.theheart.org/article/1029183.do on Nov 27, 2009.

Rassen JA, Choudhry NK, Avorn J, et al. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation 2009; 120:2322-2329.

Juurlink DN. Proton pump inhibitors and clopidogrel. Putting the interaction into perspective. Circulation 2009; 120:2310-2312.