Variability in Individual Responsiveness to Clopidogrel

• Published in: Journal of the American College of Cardiology Vol. 49; no. 14; pp. 1505 - 1516
• Main Authors: Angiolillo, Dominick J., Fernandez-Ortiz, Antonio, Bernardo, Esther, Alfonso, Fernando, Macaya, Carlos, Bass, Theodore A., Costa, Marco A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 10.04.2007
• Subjects: Cardiovascular; Internal Medicine; GTP; NSTE-ACS; PGE1; GP; cAMP; ADP; VASP-P; ACS; MFI; PCI; LTA; STEMI; CYP; ATP; percutaneous coronary intervention; acute coronary syndrome; adenosine diphosphate; non–ST-segment elevation acute coronary syndrome; prostaglandin E 1; guanosine triphosphate; cytochrome P450; light transmittance aggregometry; vasodilator-stimulated phosphoprotein-phosphorylation; median fluorescence intensity; cyclic adenosine monophosphate; adenosine triphosphate; PGE 1; glycoprotein; ST-segment elevation myocardial infarction
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2006.11.044

Variability in Individual Responsiveness to Clopidogrel: Clinical Implications, Management, and Future Perspectives Dominick J. Angiolillo, Antonio Fernandez-Ortiz, Esther Bernardo, Fernando Alfonso, Carlos Macaya, Theodore A. Bass, Marco A. Costa Several studies have shown a broad variability in individual responsiveness to clopidogrel. Notably, there is a growing degree of evidence that recurrence of ischemic complications may be attributed to poor response to this antiplatelet agent. This paper reviews the impact of individual response variability to clopidogrel on clinical outcomes and current and future directions for its management. 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.