| Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. | |
| | |
MedLine Citation:
|
PMID: 20083681 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: The cytochrome P450 (CYP) 2C19 isoenzyme plays an important role in clopidogrel metabolization. A recently explored CYP2C19*17 allelic variant has been linked to increased transcriptional activity, resulting in extensive metabolization of CYP2C19 substrates, which may lead to an enhanced platelet response to clopidogrel treatment. The aim of this study was to assess the impact of CYP2C19*17 on ADP-induced platelet aggregation, the risk of bleeding, and stent thrombosis in clopidogrel-treated patients undergoing percutaneous coronary intervention. METHODS AND RESULTS: The study population included 1524 patients undergoing percutaneous coronary intervention after pretreatment with 600 mg clopidogrel. Genotypes were determined with a TaqMan assay. ADP-induced platelet aggregation was assessed on a Multiplate analyzer. The primary clinical safety end point was the 30-day incidence of bleeding defined according to Thrombolysis in Myocardial Infarction criteria, and the primary clinical efficacy end point was the 30-day incidence of stent thrombosis. For both heterozygous (*wt/*17; n=546) and homozygous (*17/*17; n=76) allele carriers, significantly lower ADP-induced platelet aggregation values were found compared with wild-type homozygotes (*wt/*wt; n=902; P=0.039 and P=0.008, respectively). CYP2C19*17 allele carriage was significantly associated with an increased risk of bleeding; the highest risk was observed for CYP2C19*17 homozygous patients (P=0.01, chi(2) test for trend). Multivariate analysis confirmed the independent association of CYP2C19*17 allele carriage with platelet aggregation values (P<0.001) and the occurrence of bleeding (P=0.006). No significant influence of CYP2C19*17 on the occurrence of stent thrombosis was found (P=0.79). CONCLUSIONS: CYP2C19*17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding. |
| | |
Authors:
|
Dirk Sibbing; Werner Koch; Daniela Gebhard; Tibor Schuster; Siegmund Braun; Julia Stegherr; Tanja Morath; Albert Schömig; Nicolas von Beckerath; Adnan Kastrati |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-18 |
Journal Detail:
|
Title: Circulation Volume: 121 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-02-03 Completed Date: 2010-03-11 Revised Date: 2010-10-08 |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 512-8 Citation Subset: AIM; IM |
Affiliation:
|
Deutsches Herzzentrum München, Lazarettstrasse 36, 80636 München, Germany. dirk@sibbing.net |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Aryl Hydrocarbon Hydroxylases / genetics*, metabolism Coronary Artery Disease / therapy* Coronary Thrombosis / prevention & control* Female Follow-Up Studies Gene Frequency / genetics Genotype Hemorrhage / epidemiology* Heterozygote Humans Male Middle Aged Multivariate Analysis Platelet Aggregation / genetics* Platelet Aggregation Inhibitors / therapeutic use Polymorphism, Genetic / genetics Risk Factors Stents* Ticlopidine / analogs & derivatives*, metabolism, therapeutic use Treatment Outcome |
| Chemical | |
Reg. No./Substance:
|
0/Platelet Aggregation Inhibitors; 55142-85-3/Ticlopidine; 90055-48-4/clopidogrel; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C19 protein, human |
| Comments/Corrections | |
Comment In:
|
Circulation. 2010 Feb 2;121(4):481-3
[PMID:
20083686
]
Circulation. 2010 Oct 5;122(14):e478; author reply e479 [PMID: 20921447 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Arterial stiffness and cardiovascular events: the Framingham Heart Study.
Next Document: Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction.