Effects of the rs2244613 polymorphism of the CES1 gene on the antiplatelet effect of the receptor P2Y12 blocker clopidogrel

2019 ◽  
Vol 34 (3) ◽  
Author(s):  
Karin B. Mirzaev ◽  
Darya V. Osipova ◽  
Elena J. Kitaeva ◽  
Vladimir V. Shprakh ◽  
Sherzod P. Abdullaev ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Carrier Rate ◽  
Chain Reaction ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
Polymerase Chain ◽  
Healthy Participants ◽  
Ces1 Gene

Abstract Background The aim of this study was to evaluate the association of the carriage of the rs2244613 polymorphism of the CES1 gene with clopidogrel resistance as well as to evaluate the effectiveness of antiplatelet therapy in the carriers of this marker who have had acute coronary syndrome (ACS). This study also analyzes the procedure of percutaneous coronary intervention and compares the rs2244613 carrier rate between patients with ACS and healthy participants. Methods The study involved 81 patients diagnosed with ACS and 136 conditionally healthy participants. The optical detection of platelet agglutination by VerifyNow was employed to measure residual platelet reactivity in patients with ACS. The rs2244613 polymorphism was determined using real-time polymerase chain reaction. Results According to the results, the AA genotype of the rs2244613 polymorphism of the CES1 gene was detected in 37 patients (45.6%), the CA genotype in 42 patients (51.8%) and the CC genotype in 2 patients (2.6%). The level of residual platelet reactivity in rs2244613 carriers was higher compared with patients who did not have this allelic variant: 183.23 PRU ± 37.24 vs. 154.3 PRU ± 60.36 (p = 0.01). The frequencies of the minor allele C were 28.4% and 28.3% in patients with ACS and healthy participants, respectively. The results of the linear statistical model PRU due to CES1 genotype were as follows: df = 1, F = 6.96, p = 0.01). The standardized beta was 0.285 (p = 0.01) and R2 was 0.081. However, we also added CYP2C19*2 and *17 into the linear regression model. The results of the model were as follows: df = 3, F = 5.1, p = 0.003) and R2 was 0.166. Conclusions We identified a statistically significant correlation between the carriage of the rs2244613 polymorphism of the CES1 gene and the level of residual platelet aggregation among patients with ACS and the procedure of percutaneous coronary intervention.

scholarly journals Does Baseline On-treatment Platelet Reactivity Impact Long-term Prognosis in Patients with Acute Coronary Syndrome and Thrombocytopenia Who Underwent Percutaneous Coronary Intervention?

2021 ◽  
Author(s):  
Ru Liu ◽  
Tianyu Li ◽  
Deshan Yuan ◽  
Yan Chen ◽  
Xiaofang Tang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Real World ◽  
Cox Regression ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
The Real ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Abstract Objectives: This study analyzed the association between on-treatment platelet reactivity and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. Methods: A total of 10724 consecutive cases with coronary artery disease who underwent percutaneous coronary intervention (PCI) were collected from January to December 2013. Cases with ACS and TP under dual anti-platelet therapy were enrolled from the total cohort. 5-year clinical outcomes were evaluated among cases with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), tested by thromboelastogram (TEG) at baseline. Results: Cases with HTPR, LTPR and NTPR accounted for 26.2%, 34.4% and 39.5%, respectively. Cases with HTPR were presented with the most male sex, lowest hemoglobin level, highest erythrocyte sedimentation rate and most LM or three-vessel disease, compared with the other two groups. The rates of 5-year all-cause death, major adverse cardiovascular and cerebrovascular events (MACCE), cardiac death, myocardial infarction (MI), revascularization, stroke and bleeding were all not significantly different among three groups. Multivariable Cox regression indicated that, compared with cases with NTPR, cases with HTPR were not independently associated with all endpoints, as well as cases with LTPR (all P>0.05). Conclusions: In patients with ACS and TP undergoing PCI, 5-year all-cause death, MACCE, MI, revascularization, stroke and bleeding risk were all similar between cases with HTPR and cases with NTPR, tested by TEG at baseline, in the real world. The comparison result was the same between cases with LTPR and NTPR.

On-ticagrelor platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome

2020 ◽  
Author(s):  
marc laine ◽  
Vassili PANAGIDES ◽  
Corinne Frère ◽  
thomas cuisset ◽  
Caroline Gouarne ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Clinical Outcome ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
The Relationship

Background: A strong association between on-thienopyridines platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting. Objectives: We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI. Methods: We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction and urgent revascularization. Results: We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥ 2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥ 2 or with MACE (p=0.12 and p=0.56, respectively). No relationship between PR and outcomes was observed, neither when PR was analyzed quantitatively nor qualitatively (low on-treatment PR (LTPR) vs no LTPR). Conclusion: On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.

scholarly journals Modern Antiplatelet Therapy for Percutaneous Coronary Intervention. How to Make the Right Choice?

2020 ◽  
Vol 16 (6) ◽  
pp. 1017-1023
Author(s):  
T. M. Uskach ◽  
A. S. Tereshchenko
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Invasive Treatment ◽  
St Segment Elevation ◽  
Coronary Syndrome ◽  
St Segment ◽  
Percutaneous Coronary

Dual antiplatelet therapy is the most important step in acute coronary syndrome (ACS) treatment. The new generation of inhibitors of P2Y12 platelet receptors (prasugrel and ticagrelor) provide more pronounced platelet inhibition than clopidogrel. The drugs differ in pharmacodynamics and platelet reactivity tests due to different mechanisms of binding to P2Y12 receptors. The antiplatelet effect of prasugrel and ticagrelor provides clinical benefit and better prognosis in patients with various forms of ACS. In patients with ST-segment elevation ACS prasugrel and ticagrelor are preferred over clopi-dogrel due to their higher efficacy and better clinical outcomes, and currently have preferential positions in guidelines compared to clopidogrel. The comparison of prasugrel versus ticagrelor (ISAR-REACT 5 trial) demonstrated superiority of prasugrel over ticagrelor in patients with ST-segment elevation ACS, for whom an invasive evaluation is planned and in early invasive treatment non-ST-segment elevation ACS. The choice of a drug for dual antiplatelet therapy in various clinical situations remains controversial. The latest ESC guidelines on non-ST elevation ACS (2020) [1] demonstrate the possible preference for prasugrel in patients with ACS without ST-segment elevation undergoing percutaneous coronary intervention. Current article demonstrates the results of recent clinical studies and the real clinical data regarding antiplatelet therapy in patients with coronary interventions. The indications for the use of P2Y12 platelet inhibitors in certain groups of patients are outlined. Treatment selection of the most effective and safe drugs in patients with ACS is highlighted according to the updated European guidelines.

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