Antiplatelet Drug Resistance and Variability in Response: The Role of Antiplatelet Therapy Monitoring
Udaya S. Tantry and Paul A. Gurbel
Affiliation: Sinai Center for Thrombosis Research, Cardiac Catheterization Laboratories, Sinai Hospital of Baltimore, 2401 W. Belvedere Ave, Baltimore, MD 21215.
Dual antiplatelet therapy of clopidogrel added aspirin is an established treatment strategy to prevent recurrent ischemic event
occurrence in coronary artery disease patients. Generally, a one size fits all nonselective strategy is used without an assessment of pharmacodynamic
efficacy of clopidogrel therapy. However, pharmacodynamic studies revealed various limitations of clopidogrel metabolism
and numerous factors such as genetic and, drug-drug interactions influence the antiplatelet response to clopidogrel therapy. Translational
platelet function investigations performed in the percutaneous coronary intervention (PCI)-treated population receiving clopidogrel
have identified high platelet reactivity (HPR) to adenosine diphosphate as a major risk factor for both acute as well as long-term ischemic
event occurrence, including stent thrombosis. Recent studies have highlighted the relation of single nucleotide polymorphisms of genes
involved in clopidogrel absorption and metabolism to reduced pharmacokinetic and pharmacodynamic responses to clopidogrel. Cytochrome
(CYP) 2C19 loss-of-function (LoF) allele carriage has been associated with increased thrombotic risk in the PCI population.
However, clopidogrel is pharmacodynamically effective in about two thirds of patients undergoing PCI; these patients do not have HPR.
Therefore, selectively treating two thirds of patients with generic clopidogrel may provide significant cost savings. Unselected therapy
with the new P2Y12 receptor blockers is associated with increased bleeding. The introduction of generic clopidogrel holds the strong possibility
of inducing a change in practice whereby genetic and platelet function testing are performed more frequently in patients receiving
Keywords: Antiplatelet therapy, coronary artery disease, P2Y12 receptor blockers, clopidogrel, prasugrel, ticagrelor, Loss-of-function allele.
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