Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3

The platelet P2Y12 receptor is the target of clopidogrel therapy, which has been shown to reduce thromboembolic complications of atherosclerotic disease but has limitations in terms of variability of response and irreversibility of effect. This receptor is also a target for ticagrelor (AZD6140), the first reversibly binding oral P2Y12 receptor antagonist that does not require metabolic activation and yields more consistent inhibition of platelet aggregation than clopidogrel therapy. Single nucleotide polymorphisms (SNPs) have been described in the gene for this receptor (P2RY12), some of which have been associated with variability in platelet reactivity. SNPs in P2RY1 and ITGB3 have also been reported by some groups to affect platelet reactivity to adenosine diphosphate (ADP). We assessed whether SNPs in these genes influenced the pharmacodynamic response to ticagrelor in patients enrolled in both the DISPERSE study (stable atherosclerotic disease) and the DISPERSE2 study (non-ST-segment elevation acute c...