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Recent developments in clopidogrel pharmacology and their relation to clinical outcomes

Paul A Gurbel1, Mark J Antonino, Udaya S Tantry

  • 1Sinai Hospital of Baltimore, Sinai Center for Thrombosis Research, 2401 W Belvedere Avenue, Baltimore, MD 21215, USA. pgurbel@lifebridgehealth.org

Expert Opinion on Drug Metabolism & Toxicology
|July 7, 2009
PubMed

Insights

Clopidogrel and aspirin therapy for cardiovascular disease has variable effectiveness due to patient non-responsiveness. Personalized antiplatelet strategies, guided by platelet function, can improve outcomes and reduce thrombotic events.

Area of Science:

  • Cardiovascular Pharmacology
  • Translational Medicine
  • Clinical Pharmacy

Background:

  • Oral antiplatelet therapy with clopidogrel and aspirin is standard for preventing ischemic events in cardiovascular disease.
  • Despite widespread use, thrombotic events like stent thrombosis remain high (>10%), indicating limitations in current 'one-size-fits-all' approaches.

Purpose of the Study:

  • To investigate the causes of clopidogrel response variability and its clinical implications.
  • To explore personalized antiplatelet treatment strategies to overcome current limitations.

Main Methods:

  • Review of pharmacodynamic and translational research studies.
  • Analysis of factors contributing to clopidogrel pharmacokinetic variability, including gene polymorphisms (ABCB1, CYP450) and drug absorption.
  • Evaluation of personalized treatment approaches based on platelet function testing.

Main Results:

  • Significant patient variability in clopidogrel response exists, with a substantial percentage showing non-responsiveness.
  • Clopidogrel non-responsiveness is linked to higher risks of adverse clinical events.
  • Variability is primarily pharmacokinetic, stemming from issues with active metabolite generation due to genetic factors and absorption.

Conclusions:

  • Clopidogrel non-responsiveness is a significant clinical issue.
  • Personalized antiplatelet therapy, using higher doses or alternative agents based on individual platelet function, offers a promising strategy to improve treatment efficacy and patient outcomes.

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