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New Problems With Plavix Effects

Plavix May Not Be Sufficiently Effective in Many

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Updated June 15, 2014

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

Two new problems have emerged that concern many patients taking the commonly-prescribed drug Plavix.

Plavix (clopidogrel) is an important anti-platelet drug that is used extensively in the treatment of heart disease to help prevent blood clotting (thrombosis) in the coronary arteries. Plavix is most often used in treating acute coronary syndrome (ACS), which encompasses conditions like acute heart attack and unstable angina, and after the placement of stents in order to prevent stent thrombosis. Plavix is the second most-prescribed drug in the United States.

New concerns have now been raised, however, regarding two common risk factors that appear to substantially reduce the effectiveness of Plavix. Patients with either of these risk factors who are taking Plavix appear to have a significantly higher risk of coronary artery thrombosis than those treated with Plavix who do not have the risk factors.

The first risk factor is a genetic variant (specifically, having one of the CYP2C19 alleles). As it turns out, this is quite a common genetic variant, occurring in 30% of individuals of European ancestry, 40% of African ancestry, and more than 50% of Asian ancestry. Studies have now suggested that patients with this genetic variant have a significantly higher risk of stent thrombosis and heart attack (despite Plavix therapy) than people without it.

The second risk factor is the use of proton-pump inhibitor (PPIs) -- drugs that reduce stomach acid -- along with Plavix. Plavix often causes heartburn symptoms, so PPIs have been prescribed commonly in people taking this drug. PPIs available by prescription include Prilosec and Zegerid (omeprazole), Prevacid (lansoprazole), Protonix (pantoprazole), Aciphex (rabeprazole), and Nexium (esomeprazole). Prilosec is also sold over-the-counter for heartburn.

In a study of 8205 patients with ACS, those who were discharged on both Plavix and a PPI had a 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.

Plavix is a "pro-drug." That is, before it can be used by the body, the drug needs to be metabolized to its active form. Both the genetic variant and the PPIs appear to interfere with the activation of Plavix, thus reducing its effectiveness.

The FDA has expressed concern about these new findings, and is working with the makers of Plavix (Sanofi-Aventis and Bristol-Myers Squibb) to gather as much information as they can, so that formal recommendations can be made to doctors and patients about the use of Plavix. Possible forthcoming recommendations may include routine genetic testing in patients receiving Plavix, then using higher doses of Plavix (or the now-investigational drug prasugrel instead of Plavix) in patients who have CYP2C19 variant; and avoiding PPIs whenever possible.

In the meantime, if you are taking Plavix you should talk to your doctor about these new findings. You should avoid taking over-the-counter PPIs (specifically, Prilosec) without your doctor's permission, and should only take prescription PPIs after carefully discussing the risks and benefits. Some doctors will want their patients taking Plavix to have genetic testing.

Furthermore, if your doctor is talking to you about elective (i.e., non-emergency) stent placement, you may want to discuss the possibility of having genetic testing before agreeing to the procedure. Plavix is needed to help prevent clotting of the stent, and knowing whether Plavix is likely to be fully useful in your case may be important in deciding whether to have the procedure done.

Sources:

Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2008; DOI:10.1016/S0140-6736(08)61845-0.

FDA. Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix). available at: http://www.fda.gov/cder/drug/early_comm/clopidogrel_bisulfate.htm

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.

Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009; DOI 10.1056/NEJMoa0808227.

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