Personalized antiplatelet therapy based on clopidogrel/aspirin resistance tests in acute ischemic stroke and transient ischemic attack: Study protocol of a multi-center, single-blinded and randomized controlled trial

Wang, Jiajing; Han, Mengqi; Kuang, Jie; Tu, Jiyuan; Starcevich, Katherine; Chen, Peng; Yin, Shujuan; Chen, Jibiao; Zhang, Xiaolin; Jia, Weijie; Wu, Yifan; Yi, Yingping

doi:10.1016/j.cct.2021.106507

Cited by 4 publications

(4 citation statements)

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“…Patients in the control group underwent neither CYP2C19 genotyping nor 11‐dhTxB2 testing 17 . In the control group, doctors prescribed aspirin (100 mg/day) or clopidogrel (75 mg/day) in accordance with the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2014 and patient conditions 6,17 …”

Section: Methodsmentioning

confidence: 99%

“…If the patients had dual resistance to clopidogrel and aspirin, we recommended that the doctors use alternative medicines (ticagrelor 180 mg/day or cilostazol 200 mg/day). Patients in the control group underwent neither CYP2C19 genotyping nor 11‐dhTxB2 testing 17 . In the control group, doctors prescribed aspirin (100 mg/day) or clopidogrel (75 mg/day) in accordance with the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2014 and patient conditions 6,17 …”

Section: Methodsmentioning

confidence: 99%

“…The design and results of the trial have been published previously. 17 In brief, this was a multicentre, single-blinded, randomized controlled study conducted at 14 centres in Jiangxi Province, China, from 2019 to 2021. Patients were followed up for 90 days after randomization.…”

Section: Trial Design and Participantsmentioning

confidence: 99%

“…Details of the CYP2C19 genotyping and urinary 11-dhTxB2 measurement techniques have been described elsewhere. 17 Participants in the intervention group were genotyped for three single-nucleotide polymorphisms (SNPs) for CYP2C19 (National Center for Biotechnology Information NCBI Genome build 37.1, GenBank NG_008384), including CYP2C19*2 (681G>A, dbSNP rs4244285), CYP2C19*3 (636G >A, dbSNP rs4986893) and CYP2C19*17 (À806C>T, dbSNP rs12248560). 19,20 Genotyping of the three SNPs was performed using PCR + MassARRAY (flight mass spectrometry).…”

Section: Randomization and Interventionmentioning

confidence: 99%

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Short‐term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial

Han,

Jia,

et al. 2023

Brit J Clinical Pharma

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AimsThe aim of this study was to determine whether the testing strategy for clopidogrel and/or aspirin resistance using CYP2C19 genotyping or urinary 11‐dhTxB2 testing has an impact on clinical outcomes.MethodsA multicentre, randomized, controlled trial was conducted at 14 centres in China from 2019 to 2021. For the intervention group, a specific antiplatelet strategy was assigned based on the CYP2C19 genotype and 11‐dhTxB2, a urinary metabolite of aspirin, and the control group received nonguided (ie, standard of care) treatment. 11‐dhTXB2 is a thromboxane A2 metabolite that can help quantify the effects of resistance to aspirin in individuals after ingestion. The primary efficacy outcome was new stroke, the secondary efficacy outcome was a poor functional prognosis (a modified Rankin scale score ≥3), and the primary safety outcome was bleeding, all within the 90‐day follow‐up period.ResultsA total of 2815 patients were screened and 2663 patients were enrolled in the trial, with 1344 subjects assigned to the intervention group and 1319 subjects assigned to the control group. A total of 60.1% were carriers of the CYP2C19 loss‐of‐function allele (*2, *3) and 8.71% tested positive for urinary 11‐dhTxB2‐ indicating aspirin resistance in the intervention group. The primary outcome was not different between the intervention and control groups (P = .842). A total of 200 patients (14.88%) in the intervention group and 240 patients (18.20%) in the control group had a poor functional prognosis (hazard ratio 0.77, 95% confidence interval [CI] 0.63 to 0.95, P = .012). Bleeding events occurred in 49 patients (3.65%) in the intervention group and 72 patients (5.46%) in the control group (hazard ratio 0.66, 95% CI 0.45 to 0.95, P = .025).ConclusionsPersonalized antiplatelet therapy based on the CYP2C19 genotype and 11‐dhTxB2 levels was associated with favourable neurological function and reduced bleeding risk in acute ischaemic stroke and transient ischaemic attack patients. The results may help support the role of CYP2C19 genotyping and urinary 11‐dhTxB2 testing in the provision of precise clinical treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Trial Design and Participantsmentioning

confidence: 99%

Section: Randomization and Interventionmentioning

confidence: 99%

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Short‐term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial

Han,

Jia,

et al. 2023

Brit J Clinical Pharma

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Role and Clinical Significance of Thromboelastography-Guided Individualized Antiplatelet Therapy in Non-cardiogenic Ischemic Stroke: A Retrospective Cohort Study

Zhang

Wang

2023

Preprint

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This study examined the impact of individualized antiplatelet (IA) therapy guided by Thromboelastography (TEG) in non-cardiogenic ischemic stroke patients. The patients were divided into an IA group and a control group receiving conventional treatment. A one-year follow-up tracked mortality, bleeding events, and ischemic events. 715 patients were initially enrolled, with 684 meeting the inclusion criteria (487 in IA group, 197 in control group). IA therapy significantly reduced the composite rate of death, bleeding, or ischemic events compared to conventional therapy (7.39% vs. 15.74%, P = 0.001). The IA group showed a lower incidence of combined bleeding or ischemic events (6.98% vs. 15.32%, P = 0.001). Furthermore, the IA group had lower rates of ischemic stroke (2.46% vs. 5.58%, P = 0.04) and myocardial infarction (3.08% vs. 6.6%, P = 0.035) compared to the control group. Cox regression analysis revealed that age (hazard ratio, 1.043; 95% CI, 1.01-1.078, P = 0.011) and coronary artery disease (hazard ratio, 1.902; 95% CI, 1.147-3.153, P = 0.013) were associated with increased risk of adverse events compared to the control group. A therapy guided by platelet function testing can effectively reduce adverse events, particularly the risk of ischemic events, in the clinical prognosis of ischemic stroke. However, Caution is needed in IA therapy for elderly and coronary heart disease patients due to potential risks. Further large-scale experiments are required to validate and optimize personalized antiplatelet therapy in this population. Trial Registration clinicaltrials.gov Identifier: NCT 03471169

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A Bayesian network approach for prognostic assessment in acute mild to moderate ischaemic stroke: Insights from a Multicentre Study (Preprint)

Liu,

Mo,

Liu

et al. 2024

Preprint

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BACKGROUND Mild to moderate ischaemic stroke accounts for one-half to two-thirds of all ischaemic stroke hospitalisations worldwide, yet prognostic models to assess functional outcome after stroke remain elusive. OBJECTIVE This study aimed to identify the risk factors and develop a prognostic assessment model for short-term functional outcome in patients with acute mild-to-moderate ischaemic stroke using the Bayesian Network (BN) approach. METHODS Patients participating in a multicentre randomised controlled trial were eligible for inclusion in this study. The least absolute shrinkage and selection operator (LASSO) regression was applied to reduce the dimensionality of the data, and synthetic minority oversampling technology (SMOTE) was used to correct data imbalances. The Bayesian network model was trained using a hill-climbing algorithm to determine the optimal network structure. The area under the receiver operating characteristic curve (AUROC) and the calibration plot were used to assess model performance. RESULTS A total of 2,432 patients were included for analysis, 424（17.43%）patients had unfavorable outcome in 3-month after AIS,. The BN model identified the NIH Stroke Scale (NIHSS) score, age, C-reactive protein (CRP) levels, fasting plasma glucose (FPG), and history of stroke as significant prognostic factors. The BN model outperformed the logistic regression model in accuracy, sensitivity, and F1 score in test sets, with significant differences in the AUROC as per the DeLong test (P < 0.05). The calibration plot showed good agreement between predictions and observations in both the training and test sets. CONCLUSIONS The NIHSS score, age, CRP levels, FPG, and history of stroke are significant predictors of functional outcome in AIS patients. The BN model demonstrates superior predictive performance compared to traditional logistic regression, suggesting its potential as a valuable tool for assessing short-term prognosis in mild-moderate ischaemic stroke patients. CLINICALTRIAL The trial is registered in the Chinese Clinical Trial Registry (http://www. chictr.org.cn/, ChiCTR1900026492) on 12 October 2019.

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Personalized antiplatelet therapy based on clopidogrel/aspirin resistance tests in acute ischemic stroke and transient ischemic attack: Study protocol of a multi-center, single-blinded and randomized controlled trial

Cited by 4 publications

References 24 publications

Short‐term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial

Short‐term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial

Role and Clinical Significance of Thromboelastography-Guided Individualized Antiplatelet Therapy in Non-cardiogenic Ischemic Stroke: A Retrospective Cohort Study

A Bayesian network approach for prognostic assessment in acute mild to moderate ischaemic stroke: Insights from a Multicentre Study (Preprint)

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