Non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel by proton-pump inhibitors: A pilot study
Journal
Acta Cardiologica Sinica
Journal Volume
32
Journal Issue
2
Pages
215-222
Date Issued
2016
Abstract
Background: The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and protonpump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods: Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping? (TEG?) and vasodilator-stimulated phosphoprotein (VASP) assays. Results: Both TEG? and VASP tests showed the same general qualitative trend, but TEG? detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG? results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions: Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome. ? 2016, Republic of China Society of Cardiology. All rights reserved.
SDGs
Other Subjects
batroxobin; blood clotting factor 13; clopidogrel; cytochrome P450 2C19; esomeprazole; heparin; pantoprazole; rabeprazole; vasodilator stimulated phosphoprotein; adult; Article; blood sampling; clinical trial; coronary artery disease; enzyme metabolism; female; fibrin clot; genotyping technique; human; loading drug dose; male; normal human; pilot study; platelet reactivity; sample size; single blind procedure; single nucleotide polymorphism; thrombocyte aggregation; thrombocyte function; thromboelastography
Publisher
Republic of China Society of Cardiology
Type
journal article