Clopidogrelandpolymorphisms

1. Genetic Determinants of Response to Clopidogrel and Cardiovascular Events Nicole Cullen Noon Conference February 4, 2009

7. Absorption, mediated by intestinal efflux pump (ABCB1) Hepatic metabolization of prodrug by P450 (CYP3A5, CYP2C19) ADP receptor (P2RY12) GPIIb/IIIa receptor involved in platelet aggregation (ITGB3)

12. Results – Predictors Starting at the beginning of the study, the ABCB1 variant and two CYP2C19 LOF variants carried a significant increase in risk for an outcome event during the year (p=0.007 and p=0.003, respectively) -Remained significant after adjusting for the risk factors and treatments listed in original table ABCB1: Event rate 15.5% vs 10.7%, adjusted hazard ratio 1.72, 95% CI 1.20-2.47 For CYP2C19: Event rate 21.5% vs 13.3%, adjusted hazard ratio 1.98, 95% CI 1.10-3.58 (After propensity-score matching, risk of outcome was even higher – HR 2.14, 95% CI 1.09-4.17)

17. What our clients say... "I just wanted to call and tell you that my physician switched my medications based on my test results, and I cannot describe how much better I feel. You have made a believer out of me, my family, and my physician. I hope this testing becomes routine before anyone is placed on long term medication." - PY, Eirie , CO

23. http:// www.cardiosource.com/cvn/index.asp?videoID =826