What does this research mean for the field?

Approximately 25% of patients are nonresponders to clopidogrel, which is associated with a threefold increase in adverse clinical outcomes driven by CYP2C19 genetic polymorphisms and drug-drug interactions. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

Evaluate the pharmacogenomic and pharmacokinetic mechanisms underlying clopidogrel resistance and review the clinical significance of drug-drug interactions with proton pump inhibitors.

September 9, 2010Expert Opinion on Pharmacotherapy

Nonresponders to clopidogrel: pharmacokinetics and interactions involved

Q: What is the clinical evidence from this study?

Study design: Review. Population: Acute coronary syndromes and stent implantation. Intervention: Clopidogrel.

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Key result

Clopidogrel nonresponse is linked to ~3x more adverse outcomes driven by genetic polymorphisms and drug interactions.

Population

Patients with acute coronary syndromes and stent implantation

Design

Review

Authors

MGMariano GiorgiConsejo Nacional de Investigaciones Científicas y Técnicas GGGuillermo Di GirolamoUniversity of Buenos Aires CGClaudio GonzálezUniversity of Buenos Aires

Discussion

Member takes

Implication

May support genetic testing or alternative agents in select patients; leaves open whether routine screening improves outcomes.

Key Points

Evaluate the pharmacogenomic and pharmacokinetic mechanisms underlying clopidogrel resistance and review the clinical significance of drug-drug interactions with proton pump inhibitors.
Synthesized pharmacokinetic and pharmacogenetic evidence addressing variability in clopidogrel metabolic activation.
Assessed literature regarding CYP2C19 genetic polymorphisms, drug interactions with proton pump inhibitors, and regulatory recommendations.
Approximately 25% of individuals display nonresponsiveness to clopidogrel, conferring a threefold higher risk of adverse clinical outcomes.
Reduced bioactivation linked to CYP2C19 genetic variants and competitive inhibition by proton pump inhibitors decreases antiplatelet efficacy, though clinical outcomes data remain controversial.
Overcoming nonresponsiveness involves personalized risk-benefit evaluations, including platelet aggregability testing, genotyping, and alternative antiplatelet agents.

Structured PICO

Population

Patients with acute coronary syndromes and stent implantation

Exposure

Clopidogrel and aspirin therapy (focusing on nonresponders, CYP2C19 genetic polymorphisms, and proton pump inhibitor interactions)

Clopidogrel resistance is a multifactorial issue affecting about 25% of patients, necessitating individualized management strategies including consideration of genetic polymorphisms and drug interactions like PPIs.

Cite This Study

Giorgi et al. (2010) conducted a review in Acute coronary syndromes and stent implantation. Clopidogrel was evaluated. About 25% of subjects are nonresponders to clopidogrel, which is associated with a threefold increase in adverse outcomes driven by genetic polymorphisms and drug-drug interactions.

synapsesocial.com/papers/6aa52b0cb3a9aaf5308e30f5 https://doi.org/10.1517/14656566.2010.498820

Topics

Dual antiplatelet therapy

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