HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Google Scholar Articles by Trenk, D. Articles by Neumann, F.-J. PubMed Articles by Trenk, D. Articles by Neumann, F.-J. Related Collections Related Articles

CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Cytochrome P450 2C19 681G>A Polymorphism and High On-Clopidogrel Platelet Reactivity Associated With Adverse 1-Year Clinical Outcome of Elective Percutaneous Coronary Intervention With Drug-Eluting or Bare-Metal Stents

Dietmar Trenk, PhD^_*,_*, Willibald Hochholzer, MD^_*, Martin F. Fromm, MD, Ligia-Emilia Chialda, MD, Andreas Pahl, PhD, Christian M. Valina, MD^_*, Christian Stratz, MD^_*, Peter Schmiebusch, MD^_*, Hans-Peter Bestehorn, MD^_*, Heinz Joachim Büttner, MD^_* and Franz-Josef Neumann, MD^_*

^_* Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany.

Manuscript received September 10, 2007; revised manuscript received November 30, 2007, accepted December 10, 2007.

^_* Reprint requests and correspondence: Dr. Dietmar Trenk, Herz-Zentrum Bad Krozingen, Suedring 15, D-79189 Bad Krozingen, Germany. (Email: dietmar.trenk{at}herzzentrum.de).

Objectives: We investigated whether the loss of function CYP2C19 681G>A *2 polymorphism is associated with high (>14%) residual platelet aggregation (RPA) on clopidogrel and whether high on-clopidogrel RPA impacts clinical outcome after elective coronary stent placement.

Background: The cytochrome P450 (CYP)–dependent conversion of clopidogrel to its active metabolite may contribute to the variability in antiplatelet effect of clopidogrel.

Methods: The study included 797 consecutive patients undergoing percutaneous coronary intervention, who were followed-up for 1 year. Adenosine-diphosphate–induced (5 µmol/l) RPA was assessed after a 600-mg loading dose and after the first 75-mg maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by real-time polymerase chain reaction.

Results: Of the patients included, 552 (69.3%) were CYP2C19 wild-type homozygotes (*1/*1) and 245 (30.7%) carried at least one *2 allele. Residual platelet aggregation at baseline did not differ significantly between genotypes. On clopidogrel, RPA was significantly (p < 0.001) higher in *2 carriers than in wild-type homozygotes (23.0% [interquartile range (IQR) 8.0% to 38.0%] vs. 11.0% [IQR 3.0% to 28.0%] after loading; 11.0% [IQR 5.0% to 22.0%] vs. 7.0% [IQR 3.0% to 14.0%] at pre-discharge). Between *2 carriers and wild-type homozygotes, we found significant (p < 0.001) differences in the proportion of patients with RPA >14%, both after loading (62.4% vs. 43.4%) and at pre-discharge (41.3% vs. 22.5%). Residual platelet aggregation >14% at pre-discharge incurred a 3.0-fold increase (95% confidence interval 1.4 to 6.8; p = 0.004) in the 1-year incidence of death and myocardial infarction.

Conclusions: Patients carrying at least one CYP2C19*2 allele are more prone to high-on clopidogrel platelet reactivity, which is associated with poor clinical outcome after coronary stent placement (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236 [ClinicalTrials.gov] ).

Abbreviations and Acronyms   ADP = adenosine diphosphate   CI = confidence interval   CYP = cytochrome P450   GP = glycoprotein   MI = myocardial infarction   PCI = percutaneous coronary intervention   PCR = polymerase chain reaction   RPA = residual platelet aggregation

Related Articles

Clopidogrel Resistance: More Grist for the Mill

John A. Cairns and John Eikelboom
J. Am. Coll. Cardiol. 2008 51: 1935-1937. [Full Text] [PDF]

This article has been cited by other articles:

				J. A. Cairns and J. Eikelboom Clopidogrel Resistance: More Grist for the Mill J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1935 - 1937. [Full Text] [PDF]