Abstract
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.
Highlights
Clopidogrel is a second-generation thienopyridine antiplatelet drug which exerts its effect by the inhibition of the platelet’s purinergic receptor P2Y12 preventing adenosine diphosphate (ADP) from stimulating it
Mega et al (2010) indicated that the ATPBinding Cassette Subfamily B Member 1 (ABCB1) polymorphism is significantly associated with the risk of deaths due to cardiovascular events or stroke among acute coronary syndrome (ACS) patients treated with clopidogrel in the “Trial to Assess Improvement in the Therapeutic Outcomes by Optimizing Platelet Inhibition with PrasugrelThrombolysis in Myocardial Infarction” (TRITON-TIMI 38) trial [42]
Clopidogrel had been well established as essential antiplatelet therapy paired with aspirin in dual antiplatelet therapy (DAPT) therapy
Summary
Clopidogrel is a second-generation thienopyridine antiplatelet drug which exerts its effect by the inhibition of the platelet’s purinergic receptor P2Y12 preventing adenosine diphosphate (ADP) from stimulating it. PCI patients have to take loading dose of clopidogrel prior to procedure followed by postprocedure dual antiplatelet therapy (DAPT) of low dose aspirin and clopidogrel for duration up to 12 months based onstent type and risk assessment [2]. This DAPT therapy is pivotal to prevent stent thrombosis (ST) and recurrence of ischemic events after PCI. We aimed to review the literature on clopidogrel variable platelets reactivity and appraise current methods to assess the clopidogrel therapeutic outcome. We aimed to review the Cardiology Research and Practice literature on new approaches such as pharmacometabolomics and integrative pharmacometabolomics-pharmacogenetics in assessing clopidogrel therapeutic outcome
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