Genetics of Platelet Inhibitor Treatment

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2013 Aug 29

PMID 23981082

Citations 17

Authors

Dietmar Trenk

Willibald Hochholzer

Affiliations

Soon will be listed here.

Abstract

Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the standard of care in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) because this regimen has markedly decreased the rate of cardiovascular events. The substantial variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. Baseline demographic and clinical variables contributing to the observed variability have been identified. Besides this, research within the past decade has focused on the impact of genetic polymorphisms encoding transport systems or enzymes involved in the absorption and metabolism of these drugs. Loss-of-function polymorphisms in CYP2C19 are the strongest individual variables affecting pharmacokinetics and antiplatelet response to clopidogrel, but explain no more than 5 to 12% of the variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. No genetic variables contributing to clinical outcomes of patients treated with the newer P2Y12 receptor antagonists, prasugrel or ticagrelor, have been identified so far. This review aims to provide an update on the current status of genotype-based personalized therapy with clopidogrel.

Citing Articles

Prevalence of CYP2C19 and ITGB3 polymorphisms among Bangladeshi patients who underwent percutaneous coronary intervention.

Islam M, Nova T, Momenuzzaman N, Rabbi S, Jahan I, Binder T SAGE Open Med. 2021; 9:20503121211042209.

PMID: 34471538 PMC: 8404630. DOI: 10.1177/20503121211042209.

Clinical importance of testing for clopidogrel resistance in patients undergoing carotid artery stenting-a systematic review.

Collette S, Bokkers R, Dierckx R, van der Laan M, Zeebregts C, Uyttenboogaart M Ann Transl Med. 2021; 9(14):1211.

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Genetic testing in patients undergoing percutaneous coronary intervention: rationale, evidence and practical recommendations.

Galli M, Franchi F, Rollini F, Cavallari L, Capodanno D, Crea F Expert Rev Clin Pharmacol. 2021; 14(8):963-978.

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TMAO: a potential mediator of clopidogrel resistance.

Ma R, Fu W, Zhang J, Hu X, Yang J, Jiang H Sci Rep. 2021; 11(1):6580.

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