Individual variability in the disposition of and response to clopidogrel: pharmacogenomics and beyond

Area of Science:

• Pharmacogenomics
• Cardiovascular Medicine
• Clinical Pharmacology

Background:

• Clopidogrel, often with aspirin, improves survival in acute coronary syndrome patients.
• Patient response to clopidogrel therapy shows significant inter-individual variability.
• Both genetic and non-genetic factors contribute to this variable clopidogrel response.

Purpose of the Study:

• To explore the genetic and non-genetic factors influencing clopidogrel response variability.
• To identify knowledge gaps and future research needs for risk prediction in clopidogrel therapy.
• To enhance patient care by understanding factors leading to inadequate clopidogrel therapy.

Main Methods:

• Review of emerging data on clopidogrel response variability.
• Identification of genetic polymorphisms (e.g., CYP2C19, CYP2C9, MDR1) affecting drug metabolism and platelet function.
• Analysis of non-genetic covariates including ethnicity, gender, age, and comorbidities.

Main Results:

• Genetic polymorphisms in CYP2C19, CYP2C9, and MDR1 genes are implicated in clopidogrel bioactivation and platelet response.
• Non-genetic factors such as ethnicity, gender, age, body weight, and drug interactions also influence clopidogrel efficacy.
• Multiple genetic and non-genetic factors contribute small effects, collectively impacting overall patient response.

Conclusions:

• Understanding the interplay of genetic and non-genetic factors is crucial for personalized clopidogrel therapy.
• Further research is needed to fully delineate these factors and improve risk prediction for adverse outcomes.
• Addressing knowledge gaps will aid in optimizing clopidogrel treatment strategies for acute coronary syndrome patients.