State-of-the-Art Paper
Variability in Individual Responsiveness to Clopidogrel: Clinical Implications, Management, and Future Perspectives

https://doi.org/10.1016/j.jacc.2006.11.044Get rights and content
Under an Elsevier user license
open archive

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.

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
non–ST-segment elevation acute coronary syndrome
PCI
percutaneous coronary intervention
PGE1
prostaglandin E1
STEMI
ST-segment elevation myocardial infarction
VASP-P
vasodilator-stimulated phosphoprotein-phosphorylation

Cited by (0)

1

Dr. Angiolillo is on the speakers’ bureau and is a consultant for Sanofi-Aventis and Bristol-Myers Squibb.