Efficacy and safety of CYP2C19 genotype in stroke or transient ischemic attack patients treated with clopidogrel monotherapy or clopidogrel plus aspirin

Yao, Jia-Chen; Cui, Min; Pan, Mang-Mang; Z, Gu; Li, Wenyan

doi:10.1097/md.0000000000011060

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…Although these studies consistently suggest CYP2C19 genotypes are closely related to the clopidogrel response, the influence of CYP2C19 metabolizer status on the clopidogrel response is still inconclusive. In addition, there is no consensus as to whether the diminished pharmacologic response leads to increased clinical adverse events in patients with ischemic stroke (IS) or TIA, and whether aspirin as an alternative to clopidogrel can improve the efficacy in patients with resistance to clopidogrel therapy 14 . In this study, the clopidogrel response was investigated in stroke patients, and the response was further explored after adjustment of anti-platelet therapy according to the CYP2C19 metabolizer status.…”

Section: Introductionmentioning

confidence: 99%

Anti-Platelet Therapy in Mild Cerebral Infarction Patients on the Basis of CYP2C19 Metabolizer Status

Tang²,

Xi-Hua

et al. 2019

Cell Transplant

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This study aimed to investigate the effects of CYP2C19 metabolizer status on the clinical therapeutic efficacy of cerebral infarction. Patients with cerebral infarction ( n = 180; NIHSS score ≤ 5) were recruited and divided into Group A and Group B according to CYP2C19 metabolizer status. In Group A, patients received routine clopidogrel therapy for 1 year; in Group B, the patients with extensive metabolizer (EM) were treated with clopidogrel, and patients with intermediate metabolizer (IM) and poor metabolizer (PM) were treated with aspirin for 1 year. On admission, National Institutes of Health Stroke Scale score was determined, and the therapeutic efficacy was evaluated with Modified Rankin Scale score after 1 year of treatment. The outcomes and adverse effects were recorded during the treatment. After routine clopidogrel treatment, the efficacy in EM patients was significantly better than in PM and IM patients. After adjustment of therapeutic protocol, the therapeutic efficacy in PM and IM patients was markedly improved, which was accompanied by significant reduction in recurrence rate of cerebral infarction. Although the adverse effects increased in patients receiving aspirin treatment, they resolved after symptomatic therapy. CYP2C19 metabolizer status is closely related to the clinical efficacy of clopidogrel. Thus, it is necessary to adjust the anti-platelet treatment according to the CYP2C19 metabolizer status to maximize therapeutic efficacy without increasing recurrence and adverse effects.

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Section: Introductionmentioning

confidence: 99%

Anti-Platelet Therapy in Mild Cerebral Infarction Patients on the Basis of CYP2C19 Metabolizer Status

Tang²,

Xi-Hua

et al. 2019

Cell Transplant

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“…[6] Although the TIA episode is transient and reversible, 70% of patients are at an unstable and high-risk state, with a higher risk of relapse or short-term progression to stroke. [7,8] TIA patients are prone to developing cerebral infarction and myocardial infarction. The overall risk of TIA recurrence, myocardial infarction, and death within 90 days after TIA occurrence is as high as 25%.…”

Section: Introductionmentioning

confidence: 99%

Impaired heart rate recovery as a predictor for poor health-related quality in patients with transient ischemic attack

Wang

et al. 2019

Medicine

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We aimed to investigate heart rate recovery (HRR) in patients with transient ischemic attack (TIA) and the relationship between HRR and health-related quality of life (HRQOL). All available patients were enrolled during the enrollment period. A total of 120 patients with TIA and 120 healthy controls were included in this study. A treadmill stress test was performed to calculate the HRR. The HRR were calculated as follows: HRR 1, 2, 3, and 5 minutes = heart rate at peak during exercise − heart rate at 1, 2, 3, and 5 minutes at rest. All patients enrolled were asked to fill in the Short Form 36 Health Survey to calculate HRQOL. We found that the maximum heart rate of TIA patients was significantly higher than that of healthy controls (166 ± 11 vs. 162 ± 14 beats/min, P = .015). Similarly, maximum systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in TIA group compared with healthy control group (SBP: 172 ± 15 vs. 165 ± 14 mm Hg, P < .001; DBP: 102 ± 12 vs. 93 ± 16 mm Hg, P < .001). The HRR were significantly lower in TIA group compared with control group (TIA vs. controls, HRR1: 17 ± 7 vs. 30 ± 8 beats/min, HRR2: 32 ± 11 vs. 49 ± 9 beats/min, HRR3: 43 ± 13 vs. 63 ± 12 beats/min, HRR5: 54 ± 16 vs. 73 ± 15 beats/min, all P < .001). Multivariate analysis showed that older age ( P = .03) and high BMI ( P = .04) were risk factors associated with abnormal HRR in patients with TIA. With regard to HRQOL, we found that role limitations due to physical problems, general health, vitality, and role limitations due to emotional problems were significantly lower in patients with abnormal HRR compared with patients with normal HRR. Multivariate analysis showed that older age ( P = .04) and abnormal HRR ( P = .03) were predictors for poor HRQOL in TIA patients. HRR was impaired in patients with TIA. In addition, TIA patients with abnormal HRR suffered from a significantly poorer HRQOL. Hence, given the prognostic value of HRR, patients with TIA should be monitored to prevent cardiovascular events and to improve HRQOL.

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Dosage Optimization of Clopidogrel Via a Precision Medicine Approach: The Way Forward

et al. 2022

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Clopidogrel is a prodrug chiefly metabolized by the hepatic isoenzyme CYP2C19 to its active metabolite that inhibits the platelet aggregation. It has been proven in many populations that the genetic polymorphism of CYP2C19 has influence on the pharmacokinetic and or pharmacodynamics of this drug and resulting in high inter-individual variability in the treatment outcomes. As CYP2C19 genetic polymorphism is highly prevalent among the Asian population, the influence of the same on the pharmacokinetics and; thereby, the pharmacodynamics of clopidogrel needs more attention. Using the pharmacogenetic information for drug therapy could help overcome these issues and to optimize the dosage regimen of clopidogrel, this review advocates the precision medicine approach for reducing the clopidogrel resistance and adverse cardiovascular events.

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Efficacy and safety of CYP2C19 genotype in stroke or transient ischemic attack patients treated with clopidogrel monotherapy or clopidogrel plus aspirin

Cited by 3 publications

References 23 publications

Anti-Platelet Therapy in Mild Cerebral Infarction Patients on the Basis of CYP2C19 Metabolizer Status

Anti-Platelet Therapy in Mild Cerebral Infarction Patients on the Basis of CYP2C19 Metabolizer Status

Impaired heart rate recovery as a predictor for poor health-related quality in patients with transient ischemic attack

Dosage Optimization of Clopidogrel Via a Precision Medicine Approach: The Way Forward

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