Clopidogrel resistance and its effect on clinical outcomes in acute coronary syndrome

Abstract

Aim: The genetic polymorphism of CYP2C19 influences clopidogrel metabolism and resistance. Aim was to assess the association between CYP2C19 loss of function variation, clopidogrel resistance based on platelet reactivity units and clinical outcomes.

Methods: A total of 668 patients of Acute Coronary Sundrome (ACS) who underwent Percutaneous Coronary Intervention (PCI) were subjected to genetic screening and 143 patients undrewent platelet function test to study the association between drug metabolization and its effects based on platelet reactivity unit values.

Results: Clopidogrel resistance with CYP2C 19 loss of function variation was noted in 54.64% of patients. Clinical outcomes, such as target vessel revascularization, target lesion revascularization, in-stent restenosis, and stent thrombosis, were also studied.

Conclusion: CYP2C19 loss of function variation is strongly associated with clopidogrel resistance and adverse clinical outcomes.

Keywords: Acute coronary syndrome; CYP2C19; Clopidogrel resistance.

Fig. 1

Impact of CYP2C19 variants on enzyme activity and clopidogrel metabolism. Figure illustrates the impact of CYP2C19 genetic variants on enzyme activity and clopidogrel metabolism. The image depicts four metabolizer phenotypes: Normal (Ultra and extensive metaboliser * 1/17,*17/*17, *1/*1), Intermediate (*1/*2 or *1/*3), and Poor (*2/*2, *2/*3, or *3/*3). Enzyme activity progressively decreases from normal to poor metabolizers, represented by a color gradient from green to red. The figure demonstrates the conversion efficiency of clopidogrel to its active metabolite for each phenotype. Normal metabolizers exhibit efficient conversion and platelet inhibition, while poor metabolizers show minimal conversion and inadequate inhibition. This visual representation effectively explains why individuals with certain CYP2C19 variants may experience reduced clopidogrel efficacy, potentially increasing their risk of adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.