Associations of CYP2C19 and F2R genetic polymorphisms with platelet reactivity in Chinese ischemic stroke patients receiving clopidogrel therapy

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Suli Zhang ◽  
Jinhang Zhu ◽  
Hua Li ◽  
Fengzhen Li ◽  
Bin Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Genetic Polymorphisms ◽  
Platelet Reactivity ◽  
Stroke Patients ◽  
Clopidogrel Therapy

Risk Factors of Recurrent Ischemic Events after Acute Noncardiogenic Ischemic Stroke

2020 ◽  
Vol 25 (45) ◽  
pp. 4827-4834 ◽  
Author(s):  
Limin Zhang ◽  
Xingang Li ◽  
Dongzhi Wang ◽  
Hong Lv ◽  
Xuezhong Si ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Operating Characteristic ◽  
Control Group ◽  
Case Group ◽  
Stroke Patients ◽  
Clopidogrel Therapy ◽  
Ischemic Events

Background: A considerable proportion of acute noncardiogenic ischemic stroke patients continue to experience recurrent ischemic events after standard therapy. Aim: We aimed to identify risk factors for recurrent ischemic event prediction at an early stage. Methods : 286 non-cardioembolic ischemic stroke patients with the onset of symptoms within 24 hours were enrolled. Vascular risk factors, routine laboratory data on admission, thromboelastography test seven days after clopidogrel therapy and any recurrent events within one year were assessed. Patients were divided into case group (patients with clinical adverse events, including ischemic stokes, transient ischemic attack, myocardial infarction and vascular related mortality) and control group (events-free patients). The risk of the recurrent ischemic events was determined by the receiver operating characteristic curve and multivariable logistic regression analysis. Results: Clinical adverse events were observed in 43 patients (case group). The mean levels of Mean Platelet Volume (MPV), Platelet/Lymphocyte Ratio (PLR), Lymphocyte Count (LY) and Fibrinogen (Fib) on admission were significantly higher in the case group as compared to the control group (P<0.001). Seven days after clopidogrel therapy, the ADP-induced platelet inhibition rate (ADP%) level was lower in the case group, while the Maximum Amplitude (MA) level was higher in the case group as compared to the control group (P<0.01). The Area Under the Curve (AUC) of receiver operating characteristic(ROC) curve of LY, PLR, , Fib, MA, ADP% and MPV were 0.602, 0.614, 0.629, 0.770, 0.800 and 0.808, respectively. The logistic regression analysis showed that MPV, ADP% and MA were indeed predictive factors. Conclusion: MPV, ADP% and MA were risk factors of recurrent ischemic events after acute noncardiogenic ischemic stroke. Urgent assessment and individual drug therapy should be offered to these patients as soon as possible.

scholarly journals Triglyceride glucose index influences platelet reactivity in acute ischemic stroke patients

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yinping Guo ◽  
Jing Zhao ◽  
Yi Zhang ◽  
Lingshan Wu ◽  
Zhiyuan Yu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Platelet Reactivity ◽  
Multivariate Logistic Regression Analysis ◽  
Platelet Inhibition ◽  
Inhibition Rate ◽  
Stroke Patients ◽  
Tyg Index ◽  
Significant Difference

Abstract Aim Insulin resistance was reported to increase the risk of ischemic stroke, which can be assessed by the triglyceride glucose (TyG) index. However, it remains unclear whether the TyG index influences the platelet reactivity during the treatment of ischemic patients. Methods Ischemic stroke patients receiving dual antiplatelet therapy (DAPT) within 48 h onset were consecutively included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The top quartile of TyG index was defined as insulin resistance. The platelet reactivity was assessed by thromboelastography. The platelet inhibition rate induced by arachidonic acid (AA) or adenosine diphosphate (ADP) was used to confirm the high residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel, respectively. The association between TyG index and platelet reactivity was assessed by Kruskal–Wallis test. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. Results A total of 1002 patients were included and divided into 4 groups by quartiles of the TyG index (< 2.02; 2.02–2.27; 2.27–2.52; ≥2.52). The findings demonstrated that the maximum intensity of the clot increased, but the AA-induced platelet inhibition rate decreased, depending on the TyG index quartiles. No significant difference was found in the ADP-induced platelet inhibition rate among groups. The prevalence of aspirin HRPR increased depending on the TyG index quartile. Unlike the non-insulin resistance group, the insulin resistance group was independently associated with aspirin HRPR (OR = 1.689, 95% CI 1.14 to 2.51, P = 0.009). Conclusions In acute ischemic stroke patients taking DAPT, the elevation of the TyG index is associated with enhanced platelet reactivity and higher prevalence of aspirin HRPR. Insulin resistance assessed by the TyG index could be an independent risk factor for aspirin HRPR.

Clopidogrel High-on-Treatment Platelet Reactivity in Acute Ischemic Stroke Patients

2014 ◽  
Vol 133 (3) ◽  
pp. 396-401 ◽  
Author(s):  
Saskia H. Meves ◽  
Kay D. Schröder ◽  
Heinz G. Endres ◽  
Christos Krogias ◽  
Jan C. Krüger ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Platelet Reactivity ◽  
Stroke Patients

scholarly journals Impact of Diabetes on Platelet Function in Acute Ischemic Stroke Patients Taking Dual Antiplatelet Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yinping Guo ◽  
Yi Zhang ◽  
Jing Zhao ◽  
Lingshan Wu ◽  
Zhiyuan Yu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Significant Risk ◽  
Maximum Amplitude ◽  
Stroke Patients ◽  
Clot Strength

Objectives: Diabetes mellitus (DM) is a significant risk factor for ischemic stroke and associated with platelet reactivity. We aim to evaluate the effect of DM on platelet function in acute ischemic stroke patients taking dual antiplatelet therapy (DAPT).Methods: We consecutively included patients with acute ischemic stroke taking DAPT. Platelet function was assessed by thromboelastography and the arachidonic acid (AA) or adenosine diphosphate (ADP) induced platelet inhibition rate were used to confirmed the high-residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel. We classified patients into DM and non-DM groups. The association between DM and platelet function was assessed and the confounding factors were adjusted by propensity score matching (PSM) analysis. The independent risk factors of HRPR were determined by multivariate logistic regression analysis.Results: A total of 1,071 acute ischemic stroke patients, 712 in the non-DM group and 359 in the DM group, were included. Patients with DM had a significantly higher maximum amplitude (63.0 vs. 62.0 mm, P &lt; 0.01), ADP-induced clot strength (34.6 vs. 30.3 mm, P &lt; 0.01) and clopidogrel HRPR rate (22.6% vs. 17.3%, P = 0.038) than those without DM. Among 662 patients after PSM, the maximum amplitude (63.1 vs. 62.5 mm, P = 0.032), ADP-induced clot strength (34.6 vs. 29.3 mm, P &lt; 0.01) and clopidogrel HRPR rate (23.0% vs. 15.7%, P = 0.018) is still higher in the DM group. DM was an independent factor of clopidogrel HRPR (OR = 1.48, 95% CI: 1.03–2.07, P &lt; 0.05).Conclusions: In acute ischemic stroke patients taking DAPT, DM is associated with increased platelet reactivity and higher prevalence of clopidogrel HRPR.

Association between silent embolic cerebral infarction and continuous increase of P2Y12 reaction units after neurovascular stenting

2014 ◽  
Vol 121 (4) ◽  
pp. 891-898 ◽  
Author(s):  
Bum Joon Kim ◽  
Joo Y. Kwon ◽  
Jin-Man Jung ◽  
Deok Hee Lee ◽  
Dong-Wha Kang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Platelet Reactivity ◽  
Treatment Options ◽  
Antiplatelet Agents ◽  
Stent Insertion ◽  
Stroke Patients ◽  
Continuous Increase ◽  
Stent Length ◽  
Serial Change

Object Endovascular procedures are one of the important treatment options for steno-occlusive arteries in ischemic stroke patients. However, embolic complications after such procedures are always a concern. The authors investigated the association between serial change of residual platelet reactivity and silent embolic cerebral infarction (SECI) after endovascular treatment. Methods Ischemic stroke patients undergoing stenting of intra- or extracranial arteries were recruited prospectively. Residual platelet reactivity, represented by aspirin reaction units (ARUs) and P2Y12 reaction units (PRUs), was measured serially (6 hours before, immediately after, and 24 hours after the procedure). A loading dosage of aspirin (500 mg) and/or clopidogrel (300 mg) was given 24 hours before the procedure to patients naïve to antiplatelet agents, whereas the usual dosage (aspirin 100 mg and clopidogrel 75 mg) was continued for patients who had previously been taking these agents for more than a week. Diffusion-weighted MRI was performed before and 24 hours after the procedure to detect new SECIs. Clinical characteristics, baseline ARU and PRU values, and the change in ARU and PRU values after stenting were compared between patients with and without SECIs. Results Among 69 consecutive patients who underwent neurovascular stent insertion, 41 patients (59.4%) had poststenting SECIs. The lesion was located only at the vascular territory of the stented vessel in 21 patients (51.2%), outside the stented vessel territory in 8 patients (19.5%), and both inside and outside in 12 patients (29.3%). The occurrence of SECIs was not associated with the baseline ARU or PRU value, but was associated with PRU increase after stenting (36 ± 73 vs -12 ± 59, p = 0.007), deployment of a longer stent (31.1 ± 16.5 mm vs 21.8 ± 9.9 mm, p = 0.01), and stent insertion in extracranial arteries (78.1% vs 45.2%, p = 0.008). Stent length (OR 1.066, p = 0.01) and PRU change (OR 1.009, p = 0.04) were independently associated with the occurrence of SECI. Conclusions Residual platelet reactivity after dual antiplatelet treatment measured before stenting did not predict poststenting SECI. However, the longer stent and the serial increase of PRU values after stenting were related to SECI. Continuous increase of platelet activation after endovascular procedure may be important in poststent cerebral infarction.

scholarly journals The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review

2020 ◽  
Vol 21 (17) ◽  
pp. 6408
Author(s):  
Adam Wiśniewski ◽  
Karolina Filipska
Keyword(s):  
Ischemic Stroke ◽  
Platelet Function ◽  
Negative Impact ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Vascular Events ◽  
Clopidogrel Resistance ◽  
Clinical Databases ◽  
Clopidogrel Therapy

Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.

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