Impact of CYP2C19 Polymorphism on Platelet Function Tests and Coagulation and Inflammatory Biomarkers in Patients Undergoing Percutaneous Coronary Intervention

Abstract

Aim:Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous coronary intervention (PCI). Methods: This prospective, observational, multicenter study enrolled 104 consecutive Japanese patients undergoing elective PCI. We examined the CYP2C19 genotype, platelet function tests, the levels of coagulation and inflammatory biomarkers and the serum levels of high-sensitivity troponin T (hsTnT) before, immediately after and one, two and 28 days after PCI. Results: A total of 68 (65%) of the 104 enrolled patients were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet aggregation (PA), measured using light transmittance aggregometry and the VerifyNow ® P2Y12 system, and the platelet reactivity index (PRI) were significantly higher at all time points in the carriers than in the noncarriers (p＜0.05), whereas there were no differences in the levels of the coagulation and inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression analyses identified on-clopidogrel PA and PRI as being significant predictors of carriers of the CYP2C19 reduced-function allele. Conclusions: The present study suggests that platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of DAPT in patients undergoing elective PCI. J Atheroscler Thromb, 2014; 21:64-76.

Comparison between the Outcomes of Intracoronary and Intravenous Administration of Eptifibatide during Primary Percutaneous Coronary Intervention in Patients with Acute ST-Elevation Myocardial Infarction

“…These results can be explained by the high local concentrations of eptifibatide achieved in IC administration in comparison to the IV route. Similar to abciximab and tirofiban, eptifibatide is a GPI that blocks the final common pathway of platelet aggregation by binding to platelet GP b/ a receptors, which bind to fibrinogen and other adhesive proteins that crosslink adjacent platelets 4,[33][34][35] . It also has dose-dependent antiplatelet, dethrombotic, and anti-inflammatory features [6][7][8][34][35][36] .…”

Tailored Adjunctive Cilostazol Therapy Based on CYP2C19 Genotyping in Patients With Acute Myocardial Infarction ― The CALDERA-GENE Study ―

“…In the present study, the frequency of the carriers of at least 1 CYP2C19 reducedfunction allele was almost similar to that reported earlier by our group in different population samples. 14, 15 We could not find CYP2C19 gain-of-function alleles (*17) in the present study, so clinical studies that include large numbers of subjects are needed to determine the true frequency of CYP2C19 gain-of-function alleles (*17) in Japanese AMI patients.…”

“…14 We also reported that the platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, seem to be useful for identifying carriers of CYP2C19 reducedfunction gene variants and for monitoring the efficacy of DAPT in patients undergoing elective PCI. 15 However, it is unclear whether CYP2C19 genotype-tailored antiplatelet therapy with adjunctive cilostazol is effective in inhibiting platelet aggregation in AMI patients with CYP2C19 reduced-function alleles. We conducted the present CALDERA-GENE (Controlled Anti-pLatelet meDical thErapy based on RApid CYP2C19 GENe Evaluation in acute myocardial infarction; UMIN000008151) study, an open-label, prospective multicenter study that enrolled Japanese AMI patients who underwent primary PCI.…”

“…AMI patients with implanted stents on admission were treated with both aspirin (loading dose of 200 mg/day followed by 100 mg/day) and clopidogrel Effects of Cilostazol on CYP2C19 Polymorphism treated with DAPT plus cilostazol at 2 weeks after AMI was assumed to be 233±86, and the PRU for the group with CYP2C19 reduced-function alleles treated with DAPT was considered to be 290±81 (from the results of the CALDERA-PCI study). 15 The sample size of the 2 groups was determined by 2-tailed unpaired Student's t-test with significance level set at 0.0166, which was calculated by Bonferroni correction, with a power level of 0.80, a mean difference in those groups of 57.4, and the common withingroup standard deviation of 83.8, as mentioned before. The required sample size was 47 in each group.…”

Clinical and Laboratory Predictors of Major Adverse Cardiac Events in Patients with Ischemic Heart Disease Following Elective Percutaneous Coronary Intervention

“…В 2014 г. Nikolopoulos с соавт. опубликовали результаты мета-анализа 53 работ и продемонстрировали, что на-личие полиморфизма в гене PAI-1 приводит к повы-шению его активности в плазме, тем самым повышая риск развития ИМ [26]. Необходимо отметить, что уро-вень PAI-1 ассоциируется с высоким риском развития рестенозов и ТС после имплантации стентов с ле-карственным покрытием [27].…”