STATE-OF-THE-ART PAPER
Variability in Individual Responsiveness to ClopidogrelClinical Implications, Management, and Future Perspectives
Dominick J. Angiolillo, MD, PhD, FACC*,1,*,
Antonio Fernandez-Ortiz, MD, PhD ,
Esther Bernardo, BSc ,
Fernando Alfonso, MD, PhD ,
Carlos Macaya, MD, PhD ,
Theodore A. Bass, MD, FACC* and
Marco A. Costa, MD, PhD, FACC*
* Division of Cardiology, University of Florida-Shands Jacksonville, Jacksonville, Florida
Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
Manuscript received August 9, 2006;
revised manuscript received November 13, 2006,
accepted November 28, 2006.
* Reprint requests and correspondence: Dr. Dominick J. Angiolillo, Division of Cardiology, University of FloridaShands Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209. (Email: dominick.angiolillo{at}jax.ufl.edu).
Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions. Clopidogrel, in combination with aspirin, is currently the antiplatelet treatment of choice for prevention of stent thrombosis, and clinical trials have shown that, in high-risk patients, prolonged dual antiplatelet treatment is more effective than aspirin alone in preventing major cardiovascular events. However, despite the use of clopidogrel, a considerable number of patients continue to have cardiovascular events. Numerous in vitro studies have shown that individual responsiveness to clopidogrel is not uniform in all patients and is subject to inter- and intraindividual variability. Notably, there is a growing degree of evidence that recurrence of ischemic complications may be attributed to poor response to clopidogrel. The mechanisms leading to poor clopidogrel effects are not fully elucidated and are likely multifactorial. Although the gold standard definition to assess antiplatelet drug response has not been fully established, there is sufficient evidence to support that persistence of enhanced platelet reactivity despite the use of clopidogrel is a clinically relevant entity. This paper reviews the impact of individual response variability to clopidogrel on clinical outcomes and current and future directions for its management.
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Abbreviations and Acronyms
| | ACS = acute coronary syndrome | | ADP = adenosine diphosphate | | ATP = adenosine triphosphate | | cAMP = cyclic adenosine monophosphate | | CYP = cytochrome P450 | | GP = glycoprotein | | GTP = guanosine triphosphate | | LTA = light transmittance aggregometry | | MFI = median fluorescence intensity | | NSTE-ACS = nonST-segment elevation acute coronary syndrome | | PCI = percutaneous coronary intervention | | PGE1
= prostaglandin E1 | | STEMI = ST-segment elevation myocardial infarction | | VASP-P = vasodilator-stimulated phosphoprotein-phosphorylation |
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