Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcome Study (GeCCO)

The Medco Research Institute® is conducting a head-to-head study of Plavix^® (clopidogrel) and Effient^® (prasugrel) that measures how the effectiveness of these drugs in heart patients is impacted by their genetic make-up. The study will examine whether the 70 to 75 percent of patients who are “extensive metabolizers” of clopidogrel – because they were born with a normally functioning version of the CYP2C19 gene – have comparable outcomes to those patients taking prasugrel, a newer, higher cost drug with metabolism less dependent on genetic variations.

GeCCO is enrolling acute coronary syndrome patients who have been newly prescribed these drugs. The study will compare effectiveness of the two drugs by measuring the rate of cardiovascular deaths, nonfatal heart attacks and nonfatal strokes over a six-month period. Patients enrolled in the study using clopidogrel will be required to provide a saliva sample to determine if their genetic make-up allows them to metabolize the drug effectively. Patients using prasugrel will not need to use a gene test since the drug is metabolized by a different pathway that is not affected by genetic variations.

About 25 percent of people worldwide are born with a version of the CYP2C19 gene that produces a cytochrome P450 2C19 enzyme that is not fully functional. This cytochrome P450 2C19 enzyme metabolizes many prescription drugs, including clopidogrel. When Plavix is broken down in the body, it produces an active form of the drug that prevents clotting by making blood platelets less likely to stick together. However, people born with a version of the gene that cannot metabolize the medication efficiently may be less responsive to it, and as a result, are more likely at risk for a major cardiovascular event including heart attack or stroke.

The label for Plavix was revised in May 2009 to provide information to prescribers about how genes like CYP2C19 can affect the action of the drug and again in March 2010 to include a black box warning concerning diminished effectiveness of Plavix in poor metabolizers. The study will also collect new information on physician action taken and clinical outcomes in the 25 to 30 percent of patients who do not extensively metabolize clopidogrel because of their CYP2C19 genotype.