Has CEME solved the problem of variability in response to clopidogrel?
Cutting-edge science and differentiation
A high variability of response to clopidogrel exists among patients who have undergone percutaneous coronary intervention; a common genetic variant within the CYP2C19 gene has been shown to be associated with a worse clinical outcome in patients undergoing coronary stenting.
However, in one analysis CYP2C19 polymorphism accounted for only 12% of the variation in response. McCormack’s powerful probes show unequivocally that under certain well-defined conditions, blockade of the P2Y12 receptor by clopidogrel can be bypassed. These new teachings suggest that under these conditions there is a reversal of blockade by clopidogrel and an increase in platelet aggregatability; in other words, clopidogrel non-responsiveness.
Clinical implications of new teachings
From this analysis McCormack also shows how a simple assay can rapidly identify those patients in whom this aberrant pathway operates. Importantly, measures to restore clopidogrel efficacy can be affordably implemented. Moreover, there is the prospect for the novel development of bedside/office assays and reformulation of clopidogrel as an admixture. Given that clinician-directed measures to restore clopidogrel efficacy will be remarkably inexpensive and safe, an alternative strategy is to offer the reformulated admixture, or the prescription of the additional agent, to all patients for whom anti-platelet therapy is warranted, without assay.
Since Plavix patents have now expired there is little incentive for further investment. However, real world and point-of-care data could easily be searched for individual plasma levels of a routinely-assayed molecule. Covariate effects of this marker upon efficacy could then be demonstrated within subgroups providing a convincing demonstration of value-differentiation.
- Expansion of use within an approved indication
- Prospect of new IP with expansion of use within the existing indications
- Prospect of additional ancillary IP