Abstract 5010: Is Impact of Proton Pump Inhibitor on Platelet Reactivity to Clopidogrel A Class Effect?
Background: Concomitant administration of clopidogrel and proton pump inhibitor (PPI) is associated with the reduced effect on platelet response to clopidogrel, and increased risk of adverse outcome after stent placement in patients with acute coronary syndrome. However, it remains unknown whether all PPIs may reduce platelet inhibitory effects of clopidogrel. The aim of this study was to examine the impact of rabeprazole, which is one of PPIs and mostly not metabolized by CYP2C19, on platelet response to clopidogrel.
Methods: Adenosine diphosphate (ADP) induced platelet aggregation (PA) using light transmission aggregometer (MCM HEMA TRACER 313) was measured as response to clopidogrel in 127 patients (male 64%, age68 years) with coronary artery disease (CAD), and CYP2C19 polymorphism, which is involved with metabolism of clopidogrel and PPI, is also examined using PCR.
Results: CYP2C19 genotypes were divided into 3 groups such as homozygous extensive metabolizer (homoEM, n=46, CYP2C19*1/*1), heterozygous EM (heteroEM, n=52, *1/*2, *1/*3), and poor metabolizer (PM, n=29, *2/*2, *2/*3, *3/*3). In contrast to distribution of CYP2C19 polymorphism in Caucasian, the rate of CYP2C19 loss of function was higher in Japanese. ADP induced PA decreased significantly in homoEM, subsequently heteroEM, and was not well inhibited in PM (PA; 3250+/−1800, 4250+/−1300, and 5010+/−1370, respectively). However, ADP induced PA was not significantly different between patients treated with (n=29; PA=4637 +/−1800) and without rabeprazole (n=98; PA=3980 +/−1159). Moreover, there were no differences in ADP induced PA between groups with and without rabeprazole, in each subgroup categorized according to the genotype of CYP2C19. As to clinical events, the intake of PPI was not associated with increased risk of mortality and stent thrombosis in patients treated with stent delivery.
Conclusion: In contrast to the reported negative PPI-clopidogrel drug interaction, the intake of rabeprazole is not associated with impaired response to clopidogrel and increased risk of mortality and stent thrombosis in patients with CAD.