Plavix

Enhancing Cardiology Patient Care
Clopidogrel & CYP2C19 Testing

Clopidogrel (Plavix) is given to patients with Acute Coronary Syndrome and especially after stent placement procedures.

Up to 30% of patients treated with standard doses of Plavix respond poorly, thus increasing their risk of recurrent ischemic events.¹

To determine if you are a poor metabolizer of Plavix, and to know your risk, requires having the CYP2C19 molecular test performed. Tens of thousands of Plavix users have had the test completed, and you deserve to know how well the medication may be working for you.

Our test applies to medications you take now, or in the future, that require the CYP2C19 pathway in your liver. These other tests include Warfarin and your sensitivity to Warfarin, along with your genetic risk of "blood clotting" that can be evaluated by the Factor II and Factor V Leiden Tests.

A Plavix warning label informs patients identified as poor CYP2C19 metabolizers about increased risks of cardiovascular events.²

Plavix

PLAVIX is a pro-drug, which requires metabolism by the hepatic cytochrome CYP2C19 to form the active thiol metabolite. The function of this enzyme can be compromised, either through direct drug inhibition or dysfunctional genetic variants that lower enzyme activity, thus the effectiveness of PLAVIX could diminish correspondingly.

Pharmacogenetics – CYP2C19 Poor Metabolisers: In patients who are CYP2C19 poor metabolisers, PLAVIX at recommended doses forms less of the active metabolite of clopidogrel and has a smaller effect on platelet function. Poor metabolisers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with PLAVIX at recommended doses may exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolisers (see ACTION AND CLINICAL PHARMACOLOGY - Pharmacokinetics, Pharmacogenetics, and Dosage and Administration).
"At this moment in time in cardiovascular medicine, this is perhaps the most striking, practical pharmacogenetic relationship demonstrated (2C19 & Plavix). It has very significant practical implications for managing patients, especially since Plavix is the second most prescribed drug in the world...Genotyping could be incorporated into daily practice. If two million patients are getting stents annually, then some 700,000 individuals are at increased risk for stent thrombosis based on their genetics.
DR. ERIC TOPOL, Director - Scripps Translational Science Institute

Why do you need to know?

Cytochrome P450 Polymorphisms and Response to Clopidogrel

New England Journal of Medicine

Carriers of CYP2C19 genetic variations exhibited:

  • 53% increased risk in death from cardiovascular causes, MI and Stroke.
  • Increased risk of stent thrombosis by a factor of 3.

We have shown that genetic variation has an effect on pharmacological and clinical responses to Clopidogrel. Carriers of a reduced-function 2C19 allele have...a higher rate of major adverse cardiovascular events..."³

Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers.³

“A DNA Test 2C19 status would identify the subgroup of patients who would be resistant to Plavix. This would be actionable by giving a higher dose of the drug, or a different drug.”
LAWRENCE LESKO, FDA Director of Office of Clinical Pharmacology

September 28, 2010

Vanderbilt Launches New Genetic Screening Program to Prevent Problems Associated with Plavix, the Most Commonly Prescribed Clot-Preventing Drug for Heart Patients

Vanderbilt University Medical Center has launched a pharmacogenomics testing program..."all heart disease patients... will receive genetic testing to determine their response to antiplatelet drug Plavix." Read more

  • (1.) Simon T. et al., "Genetic Determinants of Response to Clopidogrel and Cardiovascular Events", N Engl J Med 2009; 360: 363-375
  • (2.) Bristol Myers Squibb Canada. Product Monograph. Plavix. Clopidogrel Tablets, Manufacturers Standard.. Sanofi-Aventis Canada Inc. 2012. 1-54.
  • (3.) Mega JL, et al., "Cytochrome P-450 Polymorphisms and Response to Clopidogrel", N Engl J Med 2009; 360: 354-362