More Concern About Plavix and Proton-Pump-Inhibitors

A few weeks ago, we pointed out two new problematic issues that had been raised about the use of Plavix (clopidogrel) after stent placement. Both problems appear to reduce the effectiveness of the drug. (Plavix is used to prevent blood clotting - and subsequent blockage of the coronary artery - at the site of stent placement.) The first new problem was the discovery of a common genetic variant, shared by 30 - 50% of the population, that appears to interfere with Plavix. And the second is the discovery that commonly used proton-pump-inhibitors (PPIs, drugs that reduce stomach acid) also seem to interfere with the drug.

A new study has now been published that seems to confirm that there may be a problem between PPIs and Plavix. In this latest study, a retrospective analysis of 8205 patients published in the March 4 issue of the Journal of the American Medial Association, patients with acute coronary syndrome (ASC) who were discharged on both Plavix and a PPI had a statistically significant, 25% increased risk of death or rehospitalization for recurrent ACS than patients treated with Plavix alone. Notably, 64% of the patients in this study had been given both drugs.

A consensus document developed by the American College of Cardiology, the American Heart Association, and the American College of Gastroenterology published just a few months ago recommends PPIs as the "mainstay" of therapy to treat and prevent gastric ulcers and bleeding in patients on antiplatelet therapy like Plavix. This recommendation probably explains why the majority of patients receiving Plavix also appear to be getting PPIs.

The FDA is actively studying the advisability of prescribing PPIs (and other drugs) in patients taking Plavix. Until this agency releases formal recommendations, however, anyone taking both Plavix and a PPI ought to talk with their doctor about whether the PPI drug is still a good idea in light of this new information.

PPIs available by prescription include omeprazole (Prilosec, Zegerid), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and esomeprazole (Nexium). Prilosec is also sold over-the-counter for heartburn, and was the most commonly used PPI in this new study.

_Sources:

Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301:937-944.