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.
BACKGROUND
The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump 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(TM) (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.


BACKGROUND
Clopidogrel • CYP2C19 polymorphism • Platelet aggregation • Proton pump inhibitors • TEG • VASP.
Division of Cardiology, Department of Internal Medicine; ; Department of Laboratory Medicine, National Taiwan University College of Medicine and Hospital; ; Graduate Institute of Biomedical Electronics and Bioinformatics, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan.
Jen-Kuang
JK
Lee
Division of Cardiology, Department of Internal Medicine;
Cho-Kai
CK
Wu
Division of Cardiology, Department of Internal Medicine;
Jyh-Ming
JM
Juang
Division of Cardiology, Department of Internal Medicine;
Chia-Ti
CT
Tsai
Division of Cardiology, Department of Internal Medicine;
Juey-Jen
JJ
Hwang
Division of Cardiology, Department of Internal Medicine;
Jiuun-Lee
JL
Lin
Division of Cardiology, Department of Internal Medicine; ; Department of Laboratory Medicine, National Taiwan University College of Medicine and Hospital;
Fu-Tien
FT
Chiang