Author + information
- Received September 10, 2007
- Revision received November 30, 2007
- Accepted December 10, 2007
- Published online May 20, 2008.
- 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⁎
- ↵⁎Reprint requests and correspondence:
Dr. Dietmar Trenk, Herz-Zentrum Bad Krozingen, Suedring 15, D-79189 Bad Krozingen, Germany.
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).
This study was supported by a grant from the Herz-Zentrum, Bad Krozingen, Germany.
- Received September 10, 2007.
- Revision received November 30, 2007.
- Accepted December 10, 2007.
- American College of Cardiology Foundation