F2R Polymorphisms and Clopidogrel Efficacy and Safety: Another Step Toward Precision Medicine

摘要: By definition, precision medicine aims to prevent, diagnose, and optimize individualized treatments on the basis of each patient's individual genetic makeup. While broad clinical application such efforts remains somewhat limited, this is not true regarding antiplatelet anticoagulation therapeutics. Given central role that these medications play in primary secondary prevention numerous cardiovascular disorders, considerable understand drivers influencing their effectiveness adverse outcomes, primarily bleeding risk, have been performed successfully over last decade. Specific clopidogrel, despite its proven benefits, it has shown ∼4%–30% patients do respond adequately drug, resulting high on-treatment platelet reactivity increased rates events.1–3 Clopidogrel, being a prodrug, requires several hepatic enzymes metabolize into both biologically active inactive derivatives. Numerous prior investigations CYP2C19 enzyme major contributor generation bioactive metabolite.1,2,4 Consistent with observation, loss function (LOF) gain variants consistently associated clopidogrel efficacy.