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February 2, 2023Frontiers in Cardiovascular MedicineOpen Access

Mutant heterozygous genotype (OR 2.893; 95% CI 1.456–5.748; p = 0.002), mutant homozygous genotype (OR 4.741; 95% CI 1.828–12.298; p = 0.001), and high HCY levels (OR 1.209; 95% CI 1.072–1.362; p = 0.002) were significantly associated with clopidogrel resistance.

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Why the study?

Certain genetic and non-genetic factors may impair platelet inhibition by clopidogrel, prompting investigation into the effect of CYP2C19 polymorphism and clinical factors on platelet response in acute ischemic stroke.

Do CYP2C19 gene polymorphisms and other clinical factors influence the pharmacological response to clopidogrel in patients with acute ischemic stroke?

Population

214 patients with AIS receiving clopidogrel 75 mg daily at Ningbo First Hospital

Comparison

Clopidogrel-resistant vs clopidogrel-sensitive groups across CYP2C19 genotypes and clinical factors

Design

Observational cohort study

Authors

YMYijun MoYLYao LuFGFei Guo

Discussion

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Overview

CYP2C19 status may guide clopidogrel use in AIS; leaves open whether testing improves outcomes in trials.

Structured PICO

Do CYP2C19 gene polymorphisms and other clinical factors influence the pharmacological response to clopidogrel in patients with acute ischemic stroke?

P
Population
214 patients with acute ischemic stroke (AIS) receiving clopidogrel at a maintenance dose of 75 mg daily for more than seven days, admitted to Ningbo First Hospital. Mean age 63.16, 156 male. Key exclusions: use of glycoprotein IIb/IIIa receptor antagonists or other thienopyridines within the last week; abnormal liver, kidney, spleen, and hematopoietic function; platelet count >500 × 10^9/L or <100 × 10^9/L; malignant tumor, history of hemorrhage, or intracranial hemorrhage within the last three months; atrial fibrillation.
I
Intervention
Clopidogrel 75 mg daily for more than seven days
C
Comparator
Clopidogrel-sensitive group (platelet aggregation ≤50%) vs Clopidogrel-resistant group (platelet aggregation >50%)
O
Outcome
Clopidogrel resistance (defined as platelet aggregation >50% measured by light transmission aggregometry in response to ADP)surrogate

Carrying the CYP2C19 *2/*3 loss-of-function alleles and having high homocysteine levels are independent risk factors for clopidogrel resistance in patients with acute ischemic stroke.

Limitations

  • Single center, retrospective study
  • Subjects mainly derived from the local Han population
  • Confounding factors such as liver function, use of proton pump inhibitors, and other genetic factors not accounted for
  • Relatively small sample size with a low proportion of women
  • Light transmission aggregometry is poorly standardized and affected by numerous pre-analytical variables

Cite This Study

Mo et al. (2023) studied this question.

synapsesocial.com/papers/6a7cb53ae6f41aaf0bcf84d4https://doi.org/10.3389/fcvm.2023.1020593
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Influence of Genetic Polymorphisms on Clopidogrel Response and Clinical Outcomes in Patients with Acute Ischemic Stroke CYP2C19 Genotype on Clopidogrel Response2015 · 45 citations
  2. 2CYP2C19 Polymorphisms and Antiplatelet Effects of Clopidogrel in Acute Ischemic Stroke in China2013 · 105 citations
  3. 3Correlation study of CYP2C19 gene polymorphism and clopidogrel resistance in Han Chinese patients with cerebral infarction in Guizhou region2021 · 8 citations
  4. 4CYP2C19 polymorphism and antiplatelet effects of clopidogrel in Chinese stroke patients2013
  5. 5The Impact of CYP2C19 Loss-of-Function Polymorphisms, Clinical, and Demographic Variables on Platelet Response to Clopidogrel Evaluated Using Impedance Aggregometry2016 · 18 citations