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New Analysis Evaluated Impact of Genetic Variation on Response to Prasugrel
Date:5/5/2009

TOKYO and INDIANAPOLIS, Ind., May 5 /PRNewswire-FirstCall/ -- A new substudy from 1,466 patients from the Phase III TRITON-TIMI 38 clinical trial showed that patients who took prasugrel and had a reduced function of the CYP2C19 gene did not have an increased risk of cardiovascular death, heart attack or stroke compared with those patients who had normal function. The substudy results were published online in Circulation on May 4, 2009(1).

Prasugrel is a "prodrug" that requires the use of cytochrome P450 (CYP) enzymes to convert the drug into the active metabolite. Approximately 30 percent of Caucasians and 60 percent of Asians have reduced function in the CYP2C19 gene, which is part of the CYP system and encodes the enzymes that are responsible for converting prasugrel into its active form(2).

In the substudy, researchers examined how variation in cytochrome P450 (CYP) genes affected the response to prasugrel. In prasugrel-treated patients with acute coronary syndromes (ACS) who underwent an artery-opening procedure known as percutaneous coronary intervention (PCI), the incidence of the combined endpoint of cardiovascular death, heart attack or stroke was 8.5 percent (N=407) in those who carried at least one variant in the CYP2C19 gene that reduced its function versus 9.8 percent (N=1048) in patients without a genetic variant (P=0.27). In addition, the rate of stent thrombosis in carriers of the reduced-function variant in the CYP2C19 gene compared with non-carriers treated with prasugrel was 0.5 percent vs. 1.0 percent, respectively (P=0.48). The results also showed that rates on non-CABG-related TIMI major or minor bleeding did not significantly differ by genetic variant among those treated with prasugrel.

"It is well documented in the medical literature that particular genetic variants in the CYP2C19 gene are associated with an increased risk of cardiovascular outcomes in patients treated with c
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SOURCE Eli Lilly and Company
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