scholarly journals Both CYP2C19 and PON1 Q192R Genotypes Influence Platelet Response to Clopidogrel by Thrombelastography in Patients with Acute Coronary Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Wenxing Peng ◽  
Xiujin Shi ◽  
Xiaoyu Xu ◽  
Yang Lin
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Inhibition ◽  
Loss Of Function ◽  
Wild Type ◽  
Platelet Response ◽  
Coronary Syndrome ◽  
Normal Platelet ◽  
Q192r Polymorphism ◽  
Independent Risk Factors ◽  
The Relationship

Objective. The objective of this study is to explore the relationships of the effects of CYP2C19 and PON1 Q192R polymorphism on the activity of clopidogrel and the risk of high platelet responsiveness (HPR) by thrombelastography in patients with acute coronary syndrome (ACS). Methods. 459 ACS patients with aspirin and clopidogrel were enrolled in this observational case control study from July 13, 2015, to November 11, 2017. The patients with <30% platelet inhibition were defined as HPR group, while the others were defined as normal platelet responsiveness (NPR) group. The genotypes distribution between the groups was assessed, and the clinical impact of genetic variants was investigated by comparing the relationship between the risk of HPR and genotypes including CYP2C19⁎2, CYP2C19⁎3, CYP2C19⁎17, ABCB1, and PON1. Results. Compared with CYP2C19⁎1/⁎1 wild type carriers, CYP2C19⁎2 and ⁎3 carriers showed a significant association with the lower platelet inhibition (P=0.048). The platelet inhibition in carriers of at least one CYP2C19 loss-of-function (LOF) alleles was obviously higher than noncarriers (P=0.031). The platelet inhibition of PON1 192R carriers was lower than PON1 192Q carriers (P=0.044). Patients with the CYP2C19⁎2 and ⁎3 alleles had a greater risk of HPR than CYP2C19 wild type carriers (adjusted P=0.018 and adjusted P=0.005). At least one PON1 192R carrier predicted a significantly higher risk of HPR than PON1 192Q carriers (adjusted P=0.021). Individual CYP2C19⁎17 and ABCB1 variants did not differ significantly between the two groups. Conclusions. CYP2C19 and PON1 Q192R variants influence ADP-induced platelet inhibition by thrombelastography (TEG) in ACS patients with clopidogrel. In addition, both LOF CYP2C19 and PON1 192R variants are independent risk factors of HPR, which is measured by the relative platelet inhibition.

scholarly journals Bone marrow-derived NGFR+ cells regulate arterial remodeling and those poor mobilizations in peripheral blood in acute coronary syndrome predicts plaque progression at the non-targeted lesion

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Takashima ◽  
S Usui ◽  
S Matsuura ◽  
C Goten ◽  
O Inoue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Coronary Syndrome ◽  
Peripheral Blood ◽  
Funding Source ◽  
Arterial Remodeling ◽  
Plaque Progression ◽  
Wild Type ◽  
Plaque Volume ◽  
Coronary Syndrome

Abstract Background In our previous 5-year cohort study, we demonstrated that low gene expression of nerve growth factor receptor (NGFR) in peripheral leucocytes in acute coronary syndrome (ACS) predicted repetitive coronary interventions at the de novo lesions. An NGFR-positive cell has been demonstrated to reside in bone marrow (BM) stromal fraction and to be increased in peripheral blood mononuclear cell (MNCs) fraction in patients with ischemic heart disease. Purpose To investigate whether the BM-NGFR+ cell is associated with arterial remodeling and the relationship between the levels of peripheral NGFR+ cells after ACS and coronary plaque progression in an experimental and prospective clinical study. Methods and results In an experimental study, 8-week-old C57B6/J wild type male mice were subjected to irradiation with 9.6 Gy and transplantation with BM (BMT) isolated from GFP-transgenic NGFR wild type (WT) or knock-out (KO) mice at day 1. Four weeks after BMT, the right carotid artery was ligated for 4 weeks. Induced neointimal area was increased (p&lt;0.05), where cells under apoptosis were decreased (p&lt;0.05) in NGFR-KO-BMT group compared to WT-BMT group (n=4). NGFR+ cells were not detected in wild type sham-operated artery, whereas in the ligated artery in WT-BMT group NGFR+ cells assembled in the developed neointima and exclusively presented double positive with GFP, but absent in NGFR-KO-BMT group (p&lt;0.05, n=4). In a clinical study, thirty patients with ACS who underwent primary percutaneous coronary intervention (PCI) were enrolled. The peripheral blood sample was collected on days 0, 3 and 7, and 9 months follow-up and the number of NGFR+MNCs were measured by flowcytometric analysis. The plaque volume at non-targeted coronary lesion (non-TL:&gt;5 mm proximal or distal to the implanted stents) were quantitatively analysed using gray-scale intravascular ultrasound (IVUS) and Q-IVUS™ software at the acute phase and 9 months follow-up. The number of NGFR+MNCs in peripheral blood was 1.5-fold increased at day 3 (0.064±0.056%) compared to day 0 (0.042±0.030%) (p&lt;0.05). The change in normalized total plaque volume (TAVN) at non-TL at 9 months was negatively correlated with the number of NGFR+MNCs at day 0 (r=−0.51), day 3 (r=−0.51) and 9 months (r=−0.59) after ACS (p&lt;0.05). Multiple regression analysis showed that NGFR+MNCs at day 0 (β=−0.48, p=0.01) and CRP (β=−0.53, P&lt;0.01) are independent factors associating with TAVN change at non-TL at 9 months, regardless of LDL-cholesterol control level. ROC analysis revealed that NGFR+MNCs &lt;0.049 at day 0 predicted the increase of TAVN with AUC 0.78; sensitivity 0.82 and specificity 0.67. Conclusions Bone marrow-derived peripheral NGFR+ cells negatively regulate arterial remodeling through appropriate apoptosis of neointimal cells and the peripheral level of NGFR+ cells in ACS predicts plaque progression at the non-targeted lesion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): KAKENHI

The relationship between phobic anxiety and 2-year readmission after Acute Coronary Syndrome: What is the role of heart rate variability?

2019 ◽  
Vol 247 ◽  
pp. 73-80 ◽  
Author(s):  
Adrienne O'Neil ◽  
C. Barr Taylor ◽  
David L. Hare ◽  
Emma Thomas ◽  
Samia R. Toukhsati ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Acute Coronary Syndrome ◽  
Coronary Syndrome ◽  
Phobic Anxiety ◽  
The Relationship

A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study

Cardiology ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Cai De Jin ◽  
Moo Hyun Kim ◽  
Junghee Bang ◽  
Victor Serebruany
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Academic Research ◽  
P2y12 Receptor ◽  
Drug Eluting Stent ◽  
Platelet Response ◽  
Open Label ◽  
Korean Patients ◽  
Coronary Syndrome ◽  
Half Dose

Background: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.

scholarly journals The relationship of MicroRNA-21 and plaque stability in acute coronary syndrome

Medicine ◽  
2019 ◽  
Vol 98 (47) ◽  
pp. e18049
Author(s):  
Wangwei He ◽  
Liyuan Zhu ◽  
Yu Huang ◽  
Yinfen Zhang ◽  
Weimin Shen ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Plaque Stability ◽  
Coronary Syndrome ◽  
Relationship Of ◽  
The Relationship

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.

Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

2020 ◽  
Vol 41 (33) ◽  
pp. 3144-3152 ◽  
Author(s):  
Boris Schnorbus ◽  
Andreas Daiber ◽  
Kerstin Jurk ◽  
Silke Warnke ◽  
Jochem Koenig ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Endothelial Function ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Clinical Parameter ◽  
Mean Difference ◽  
Low Flow ◽  
Flow Mediated Dilation ◽  
Coronary Syndrome ◽  
The Impact

Abstract Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P &lt; 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73

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