A comparison of three platelet function tests in ischemic stroke patients with antiplatelet therapy

Leng

et al. 2020

PGPM

Background: There have been few studies on CYP2C19 genotypes and clopidogrel response associated with ischemic stroke (IS), especially IS complicated by type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association between CYP2C19 polymorphisms and high on-treatment platelet reactivity (HTPR) in IS patients with T2DM in China. Patients and Methods: A total of 426 consecutive IS patients with T2DM were enrolled in this case-control study and they were divided into HTPR group and non-HTPR group according to the ADP-induced platelet inhibition (PIADP) assessed by thromboelastography (TEG). Genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Various clinical and demographic data were also recorded. The association between CYP2C19 genetic variants and platelet function was assessed. Results: Carriers of CYP2C19*2 heterozygous and mutant homozygous genotypes showed significantly lower PIADP than non-carriers (27.2% vs 38.3%, p < 0.001; 27.41% vs 38.3%, p = 0.012, respectively). Compared with the control group, the CYP2C19*2 A allele was more frequent in the HTPR group (34.51% vs 25.82%, p = 0.002). The carriage of CYP2C19*2 mutant allele was significantly associated with increased risk of HTPR (odds ratio (OR) = 1.94, 95% confidence interval (CI) = 1.32-2.85). There was no significant correlation between CYP2C19*3 or *17 genotypes and HTPR risk. Conclusion: CYP2C19*2 mutant allele was associated with attenuated platelet response to clopidogrel and increased risk of HTPR in IS patients with T2DM, suggesting that CYP2C19*2 polymorphism might be an important predictor of HTPR in this high-risk population.

Section: Discussioncontrasting

confidence: 67%

Should CYP2C19 Genotyping Be Recommended as a Straight Forward Approach to Optimize Clopidogrel Utilization in Patients with Ischemic Stroke Complicated by Type 2 Diabetes Mellitus?

Leng

et al. 2020

PGPM

“…However, guidelines on PFT- or genotype-guided antiplatelet treatment are not well established given the ambiguity in studies ( 151 , 152 ). A recent comparative study on PFTs on ischemic stroke patients has demonstrated that light transmittance aggregometry arachidonic acid platelet agonist (LTA-AA) and thromboelastographic arachidonic acid platelet agonist (TEG-AA) are effective in monitoring aspirin efficacy and response ( 78 ). Dual antiplatelet therapy (DAPT), comprising clopidogrel and aspirin is an effective strategy in managing the recurrence of stroke-related events.…”

Section: Discussionmentioning

confidence: 99%

“…TEG-ADP may not be appropriate for assessing platelet function in clopidogrel users. CYP2C19 genotyping will be the better option for the detection of platelet function ( 78 ). Nevertheless, different studies showed different results: a systematic review and meta-analysis of 1,136 participants included two retrospective studies based on platelet function analysis (PFA)-guided antiplatelet therapy in recurrent stroke with or without antiplatelet therapy modified (ATM) actions ( 79 – 81 ).…”

Section: Antiplatelet Resistancementioning

confidence: 99%

Biomarkers for Antiplatelet Therapies in Acute Ischemic Stroke: A Clinical Review

et al. 2021

Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy.

“…Shao et al [13] compared three platelet function tests such as LTA (AA and ADP), TEG (AA and ADP), and PFA (EPI and P2Y) among themselves in the context of IS patients receiving antiplatelet therapy. After treatment with ASA 100 mg daily or clopidogrel 75 mg once daily or a combination of both drugs for at least 5 days.…”

Section: Monitoring Of Platelet Function During Dual Antiplatelet The...mentioning

confidence: 99%

“…For clopidogrel therapy, it is better to use a different method than TEG-ADP. In order to adjust antiplatelet therapy, it is worth combining CYP2C19 genotyping with the LTA-ADP or PFA-P2Y test [13].…”

Section: Monitoring Of Platelet Function During Dual Antiplatelet The...mentioning

confidence: 99%

The Importance of Platelets Response during Antiplatelet Treatment after Ischemic Stroke—Between Benefit and Risk: A Systematic Review

Sikora

Karczmarska-Wódzka

Bugieda

et al. 2022

IJMS

Ischemic stroke is a disease related to abnormal blood flow that leads to brain dysfunction. The early and late phases of the disease are distinguished. A distinction is made between the early and late stages of the disease, and the best effect in treating an ischemic stroke is usually achieved within the first hours after the onset of symptoms. This review looked at studies platelet activity monitoring studies to determine the risks and benefits of various approaches including antiplatelet therapy. A study was conducted on recently published literature based on PRISMA. This review includes 32 research articles directly addressing the importance of monitoring platelet function during antiplatelet therapy (dual or monotherapy) after ischemic stroke. In patients with transient ischemic attack or ischemic stroke, antiplatelet therapy can reduce the risk of stroke by 11–15%, assuming that patients respond well. Secondary prevention results are dependent on platelet reactivity, meaning that patients do not respond equally to antiplatelet therapy. It is very important that aspirin-resistant patients can benefit from the use of dual antiplatelet therapy. The individualized approach to secondary stroke prevention is to administer the most appropriate drug at the correct dose and apply the optimal therapeutic procedure to the individual patient.