Singapore, Aug 30, 2010: A new genetic sub-study of PLATO (A Study of PLATelet Inhibition and Patient Outcomes) showed that the effects on a combined primary endpoint of cardiovascular death, myocardial infarction, or stroke seen in Acute Coronary Syndromes (ACS) patients who received the investigational oral antiplatelet treatment, ticagrelor (BRILINTA), were maintained, whether or not they had the genetic variability that has been previously shown to affect a patient's response to clopidogrel. The substudy is the first to look at both efficacy and bleeding endpoints of ACS patients treated with ticagrelor who carry variations in the CYP2C19 and ABCB1 genes. The data were presented today at the European Society of Cardiology (ESC) congress in Stockholm, Sweden and simultaneously published in The Lancet.

Regardless of the CYP2C19 genotype, the primary outcome occurred less often with ticagrelor versus clopidogrel (interaction p=0.46). Ticagrelor event rates were 8.6 percent per year in carriers and 8.8 percent per year in non-carriers of CYP2C19 loss-of-function genotype. For clopidogrel patients that carried the CYP2C19 loss-of-function alleles, there was a 11.2 percent per year event rate, compared to 10.0 percent per year for patients without the loss of function allele. Similar to the overall PLATO study, total major bleeding did not significantly differ between ticagrelor and clopidogrel regardless of CYP2C19 genotype.

The genetic substudy also investigated ticagrelor and clopidogrel treatment outcomes in the three genetic groupings of the ABCB1 gene group; these were defined as high, intermediate and low expressions of ABCB1, respectively. The primary efficacy event rates for ticagrelor were: 9.5 percent per year for low, 8.5 percent per year for intermediate, and 8.8 percent per year for high expression groups. Primary efficacy event rates for clopidogrel were: 10.5 percent per year for low, 9.8 percent per year for intermediate, and 11.9 percent per year for high expression groups. There was no relationship between the ABCB1 genotype and bleeding.