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Introduction
Ticagrelor and clopidogrel are widely used as antiplatelet aggregation therapies in patients with coronary heart disease after percutaneous coronary interventions (PCIs). Clopidogrel is a prodrug converted to a pharmacologically active anti-platelet agent after metabolism by the CYP2C19 enzyme in the liver. However, in clinical practice, some patients do not achieve the desired anti-platelet action, and some may even show complete clopidogrel resistance resulting in severe adverse events including stent thrombosis, re-myocardial infarction, or death (1). Drug resistance has been attributed to CYP2C19 mutations, which mainly comprise the CYP2C19*2 and CYP2C19*3 alleles. Both of these mutant alleles can cause a decrease or complete loss of the CYP2C19 enzyme activity, influencing the efficacy of clopidogrel (2,3). The US Food and Drug Administration advises clinicians that a detection of CYP2C19 genotype and platelet function may be carried out if poor response to clopidogrel is noted. Clinical guidelines in Europe and China have also been modified for the detection of CYP2C19 genotype and platelet function in patients undergoing coronary stent implantations. However, the actual clinical significance of the test results and of the following treatment adjustment, remain unclear (4,5). The frequency of CYP2C19*2 and CYP2C19*3 mutations in the Asian population is estimated to be 57% (6). With the incidence of coronary heart disease and PCI surgery increasing annually, a higher number of Asian patients are expected to experience major cardiac adverse events (MACE) due to mutations in the CYP2C19 gene (7).
Ticagrelor is a new type of oral anti-platelet drug that can reversibly bind to adenosine receptors and exerts its anti-platelet action without in vivo metabolism. When compared with clopidogrel, ticagrelor has stronger anti-platelet aggregation effects; however, the risk of bleeding is also relatively higher. Due to the high cost and greater risk of hemorrhage, the discontinuation rate of ticagrelor is higher than that of clopidogrel.
The aim of the present study was to determine whether the antiplatelet drug regimen can be optimized by testing patients for the CYP2C19 genotype. Thus, we compared the safety and efficacy of clopidogrel vs. ticagrelor when used in patients with coronary heart disease undergoing PCI and assessed possible associations between the CYP2C19 gene polymorphism and the clinical outcomes after each treatment.
Materials and methods
Patients
A total of 971 patients with coronary...