Clopidogrel resistance - a clear problem with an unclear solution.
نویسندگان
چکیده
Over the last decade, dual antiplatelet therapy has been polymorphism and bleeding outcomes in their analysis. shown to be of significant benefit for secondary prevention in millions of patients with acute coronary syndromes (ACS), in those undergoing percutaneous coronary interventions (PCI), and in those with atrial fibrillation unable to take warfarin. Much like any other therapeutic agent, variability in response to clopidogrel was considered a reason for clinical failure leading to cardiovascular events; it was not until the 2006 firestorm related to late stent thrombosis that this issue underwent systematic study. Investigations into the pharmacokinetic (PK) and pharmacodynamic (PD) properties of clopidogrel led to the uncovering of specific genetic polymorphisms such as CYP2C19*2 and ABCB1 involved in the metabolic conversion of the pro-drug clopidogrel into its active metabolite which finally binds to the ADP receptor responsible for the antiplatelet effect. Reduced function of these alleles has since been shown to be associated with impaired PK and PD response to clopidogrel andworse clinical cardiovascular outcomes, with those homozygous for this polymorphism faring worse than those who were heterozygous, adding further biological plausibility. Given the large numbersworldwidewho need to be on clopidogrel therapy for various secondary prevention indications, even the conservative prevalence estimates for these genetic polymorphisms on the order of 25% make it a priority for clinical research. The study by Singh et al published in this issue of the Indian Heart Journal meta-analyzes 19,601 subjects from 14 studies and reaffirms the association between the CYP2C19*2 polymorphism carrier status and increased risk for major adverse cardiovascular events (MACE e RR 1.28, CI 1.06e1.54; P 1⁄4 0.009). The relation also holds for the risk of myocardial infarction and stent thrombosis; however, these results need to be interpreted in the context of significant heterogeneity between studies with respect to these outcomes. There appeared to be no relation between the CYP2C19*2
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عنوان ژورنال:
- Indian heart journal
دوره 64 4 شماره
صفحات -
تاریخ انتشار 2012