In this issue of the Journal, in a prospective, randomized, double-blind, placebo-controlled study, Gilard et al. (15) further support a potential drug–drug interaction at the CYP2C19 level. In their study of patients undergoing elective coronary stenting, co-administration of the proton pump inhibitor omeprazole with clopidogrel was associated with significantly higher platelet P2Y12 reactivity as measured by a flow cytometry assay employing monoclonal antibodies specific for vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) (15). The results support the researchers’ prior observational study (16). The VASP-P assay exploits coupling of P2Y12 to a G-protein that inhibits adenylyl cyclase. Vasodilator-stimulated phosphoprotein phosphorylation is phosphorylated by cyclic adenosine monophoshate (cAMP)-regulated protein kinases. In the assay, platelet VASP is first maximally phosphorylated by prostaglandin E1 stimulation. The assay is then repeated with the addition of ADP; a fall in the level of VASP-P after ADP stimulation serves as a marker of unblocked P2Y12 receptors and persistent P2Y12 reactivity. The determination of VASP-P has advantages over light-transmittance aggregometry as a measure of clopidogrel responsiveness by being a specific indicator of P2Y12 reactivity. Platelet aggregation in response to ADP is mediated by P2Y1 and P2Y12 and thus does not indicate only P2Y12 reactivity. In addition, platelet aggregation must be determined soon after blood drawing, whereas VASP-P is a stable marker lending potential applicability to multicenter investigations. However, it is also known (17) that VASP-P levels in platelets are influenced by nitric oxide, prostaglandins, and epinephrine through effects on cAMP levels. Nevertheless, analysis of VASP-P currently is the most specific P2Y12 assay available.