PGxHealth, a division of Clinical Data, has established a collaboration with Deutsches Herzzentrum (DHZ), Munich, to evaluate genetic markers that can predict response to anticlotting therapy Plavix (clopidogrel). The companies will conduct retrospective case/control studies to validate genetic variants including PGxHealth proprietary markers.
“Combining our efforts with PGxHealth will allow us to further evaluate genetic variants in a very large, clopidogrel-treated patient population with coronary stent placement, which includes a substantially greater number of cases than previous studies,” says Dirk Sibbing, M.D., principal investigator of the study, Deutsches Herzzentrum. “We expect these results to be extremely valuable for guiding antiplatelet therapy in the future and for determining which genetic variants predict the clinical outcome in clopidogrel-treated patients and which do not.”
Preliminary data from the studies is anticipated in 2010. The researchers will examine samples selected from a cohort of clopidogrel-treated patients that have undergone percutaneous coronary intervention (PCI) and may be at high risk for cardiovascular events if they don’t respond appropriately to clopidogrel. Platelet-function data from a significant subset of patients will also be analyzed, providing a second, direct measure of clopidogrel response.
Several known genetic variants and PGxHealth’s markers will be evaluated for association with risk of cardiovascular events in patients taking clopidogrel. Researchers will also seek to identify novel genetic predictors of clopidogrel response.
“While the role of CYP2C19 in poor response to clopidogrel is widely known, it is clear that this gene does not account for all the variability in response,” notes Marcia Lewis, vp, biomarker development at PGxHealth. Polymorphisms in several genes including CYP2C19 and other cytochrome P450 enzymes involved in clopidogrel metabolism have been associated with inadequate response to clopidogrel. Of these, only the CYP2C19*2 association is well established.