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Updated: Jun 19, 2025

Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Clopidogrel Resistance in Ischemic Stroke Patients
S Lavanya1, Dhanashri Babu, D Dheepthi
1Department of Pharmacy Practice, PSG College of Pharmacy, Peelamedu, Coimbatore, Tamil Nadu, India.
Insights
Clopidogrel resistance, a reduced drug effectiveness in stroke patients, is often linked to CYP2C19 genetic variations. Identifying this resistance is key to optimizing antiplatelet therapy and improving patient outcomes.
Area of Science:
- Cardiology
- Pharmacogenomics
- Neurology
Background:
- Stroke is a leading global cause of death, with antiplatelet drugs like clopidogrel crucial for prevention post-stroke.
- Patient response to clopidogrel varies, necessitating an understanding of clopidogrel resistance (CR).
Purpose of the Study:
- To review clopidogrel resistance in stroke patients, including its risk factors and identification methods.
- To highlight the impact of genetic polymorphisms, particularly CYP2C19, on clopidogrel efficacy.
Main Methods:
- Review of literature on clopidogrel resistance, genetic factors (CYP2C19 *2, *3), and other influencing elements.
- Discussion of diagnostic methods for assessing platelet reactivity and CR.
- Identification of alternative antiplatelet strategies.
Main Results:
- CYP2C19 genetic variants (*2, *3) are prevalent and significantly impact clopidogrel response, with carriers showing poorer outcomes.
- Factors like drug interactions (PPIs), age, sex, and comorbidities also contribute to CR.
- Platelet reactivity testing (e.g., VASP, Verify Now) can identify CR.
Conclusions:
- CYP2C19 genotyping is vital for predicting clopidogrel response in stroke patients.
- Alternative antiplatelet agents like ticagrelor may be more effective in patients with CR.
- Concurrent use of clopidogrel and proton pump inhibitors should be carefully considered.
Abstract:
Stroke remained the second leading cause of death globally in 2019. The antiplatelet drug clopidogrel is used to keep blood clots from forming in people who have experienced a stroke. Although most people find clopidogrel to be safe and beneficial, there is inevitably a range in how each patient responds. The review covers about Clopidogrel resistance in stroke patients, their risk factors and the methods to identify it. Clopidogrel resistance is characterized as the drug's inability to prevent the target enzyme from acting. The prognosis of patients with ischemic stroke and the responsiveness to clopidogrel are significantly impacted by the various genetic polymorphism CYP2C19 genotypes. The two primary mutant alleles, CYP2C19 *2 and CYP2C19 *3, have been found to be the most prevalent genotypes. Better mRS scores six months after treatment showed a higher response rate in patients without these CYP2C19 variant alleles. Other factors are drug-drug interaction (proton pump inhibitors), demographics (age, sex, social history), comorbid conditions, etc. Blood samples for testing platelet reactivity were drawn one month after discharge from a peripheral blood sample. Several methods are used to identify the clopidogrel resistance. Some of them are ADP-Induced platelet aggregation, Platelet Reactivity Index VASP, Verify Now Assay, TEG Analyzer, Plasma microRNA-223. Drugs that are not prodrugs and whose metabolism is not dependent upon CYP2C19 can be selected as a superior alternative in case of CR. Ticagrelor is one such effective substitute. Proton pump inhibitors and clopidogrel should only be used concurrently in patients with reliable clinical indications.
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