Effect of an increased clopidogrel maintenance dose or lansoprazole co-administration on the antiplatelet response to clopidogrel in CYP2C19-genotyped healthy subjects

摘要

The loss-of-function CYP2C19*2 allele is associated with a reduced ability of clopidogrel to inhibit platelet aggregation in healthy volunteers and in patients with coronary artery disease treated with a standard maintenance dose of clopidogrel (75 mg day~(-1))[1-3], and with significantly higher rates of cardiovascular outcomes, including stent thrombosis [2,4-7]. Whether the negative impact of the CYP2C19*2 allele could be reversed by using higher maintenance doses of clopidogrel is not known. The implication of CYP2C19 in clopidogrel metabolism has also been investigated in drug-drug interaction studies using various proton pump inhibitors (PPI), some of them being CYP2C19 inhibitors [8,9]. We therefore conducted the CLOVIS study (ClinicalTrials.gov number_NCT00413608) to (i) determine whether a double clopidogrel daily dose allows poor responders carrying the CYP2C19*2 allele to reach a higher platelet inhibition, and (ii) assess the impact of lansoprazole, one of the most potent CYP2C19 inhibitors among PPIs, on the pharmacodynamics of clopidogrel.