Effect of cytochrome P450 3A5 polymorphism on platelet reactivity after treatment with clopidogrel in patients scheduled for percutaneous coronary intervention

Abstract

Purpose: The aim of the present work is to study the effect of CYP3A5 polymorphism on clopidogrel response and post-stent complications among Egyptian patients scheduled for PCI. In addition, to assess post-clopidogrel platelet reactivity (PPR) as a predictor of post-stent complications. Subjects and methods: This study included 45 patients scheduled for elective PCI at Ain Shams University Hospital. All the studied patients were subjected to detection of CYP3A5 A6986G polymorphism and assessment of clopidogrel response using adenosine diphosphate (ADP)-induced platelet aggregation. Results: Wild, heterozygous and homozygous genotypes were detected in 2.2%, 31.1% and 66.7% of the patients, respectively. A trend for lower PPR in expressor genotype group was found (p = 0.08). No influence of the CYP3A5 genotypes on post-stent complications was found (p = 1.0). Clinical presentation, smoking, previous acute coronary syndrome (p < 0.05) were the main influencing factors of the PPR. Logistic regression analysis demonstrated that the stent length and PPR are the main predictors for post-stent complications (95% CI = 1.014–1.950 and 0.999–1.181; p = 0.04 and 0.05, respectively). Conclusion: CYP3A5 genetic polymorphism does not contribute to the observed variability in the inhibitory effect of clopidogrel. Low response to clopidogrel is a novel risk factor for ischemic events after PCI. The evaluation of low response to clopidogrel may help to identify patients at increased risk that may benefit from intensified antiplatelet strategy.

Keywords

• Cytochrome P450 3A5 polymorphism
• Platelet resistance
• Clopidogrel
• Percutaneous coronary intervention