Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel: The ABCD-GENE Score

JACC. Cardiovascular Interventions
Dominick J AngiolilloMatthew J Price

Abstract

The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes. Clopidogrel is the most broadly used platelet P2Y12 inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects. Although carriers of loss-of-function alleles of the cytochrome P450 2C19 enzyme have reduced clopidogrel metabolism leading to increased rates of HPR and thrombotic complications, this explains only a fraction of the pharmacodynamic response to clopidogrel, and a number of clinical factors have also been shown to have contributing roles. Three prospective and independent studies were used to: 1) develop a risk score integrating genetic and clinical factors to identify patients with HPR while on clopidogrel; 2) investigate the external validity of the risk score; and 3) define clinical outcomes associated with the risk score in a cohort of pat...Continue Reading

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Citations

Aug 25, 2020·Expert Opinion on Drug Metabolism & Toxicology·Chang Hoon LeeDominick J Angiolillo
Nov 13, 2020·Expert Opinion on Drug Safety·Mattia GalliDominick J Angiolillo
Jan 31, 2021·European Heart Journal·Niels M R van der SangenWouter J Kikkert
Mar 7, 2020·JACC. Cardiovascular Interventions·John A Bittl
Mar 22, 2021·JACC. Cardiovascular Interventions·Francesco Franchi, Fabiana Rollini
Mar 22, 2021·JACC. Cardiovascular Interventions·Naveen L PereiraMichael E Farkouh
Apr 8, 2021·JACC. Cardiovascular Interventions·Piera Capranzano, Dominick J Angiolillo
May 7, 2021·Nature Reviews. Cardiology·Julio D Duarte, Larisa H Cavallari
May 18, 2021·Expert Review of Clinical Pharmacology·Mattia GalliDominick J Angiolillo
Aug 31, 2021·European Heart Journal. Cardiovascular Pharmacotherapy·Anne H TavenierGeorge Dangas

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