Document Detail


MedLine Citation:
PMID:  19247187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The aim was to identify factors that influence the efficacy of 600 mg of clopidogrel pretreatment in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention. METHODS: In a laboratory substudy of the PRAGUE-8 trial, the influences of nonmodifiable (age and sex) and modifiable (body mass index and tobacco smoke) factors, comorbidity (hypertension, hyperlipidemia, diabetes mellitus, and renal insufficiency) and cotherapy (statin, aspirin, and heparin), on the course of clopidogrel efficacy were investigated in 105 patients pretreated with clopidogrel >or=6 hours before coronary angiography +/- percutaneous coronary intervention. Flow cytometric analysis of the vasodilator-stimulated phosphoprotein phosphorylation state was used. Independent predictors that influenced clopidogrel action were identified using linear regression. RESULTS: There was no correlation between baseline platelet reactivity index (PRI) and severity of coronary atherosclerosis; mean index of platelet reactivity for a nonsignificant lesion was 72% +/- 5.98% and for a significant lesion 70.08% +/- 8.43%. The highest proportion of low responders was patients with diabetes (50% at 28 hours). Among tobacco smokers, the response to clopidogrel occurred quickly and 80% of smokers had effective inhibition of PRI, 12 hours after drug use. After adjustments, tobacco smoking was an independent predictor for the most robust drop of PRI 12 hours after clopidogrel (P = 0.027). The magnitude of total decrease of PRI at 28 hours was not significantly influenced by cigarette smoking (P = 0.12). Linear regression showed that patients on statin therapy had a better response to clopidogrel than those without statins-the mean decrease of PRI at 28 hours was significantly higher (P = 0.02) among these patients (40.0 vs. 27.6). CONCLUSIONS: In stable coronary artery disease, no correlation exists between baseline PRI and the severity and extent of coronary atherosclerosis. A high loading dose of clopidogrel does not satisfactorily suppress enhanced PRI in patients with diabetes. Cigarette smoking is independently associated with a prompt antiplatelet response to clopidogrel. Ongoing statin therapy is an independent determinant of more effective clopidogrel-mediated inhibition of platelet reactivity.
Authors:
Zuzana Motovska; Petr Widimsky; Robert Petr; Dana Bilkova; Iuri Marinov; Stanislav Simek; Petr Kala;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  53     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-08-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  368-72     Citation Subset:  IM    
Affiliation:
Third Medical Faculty, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic. zuzana.motovska@iex.cz
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Aged
Angioplasty, Transluminal, Percutaneous Coronary*
Aspirin / therapeutic use
Body Mass Index
Cell Adhesion Molecules / metabolism
Coronary Angiography
Coronary Artery Disease / complications,  drug therapy*,  radiography,  therapy
Diabetes Mellitus, Type 2 / complications,  physiopathology
Drug Therapy, Combination
Female
Heparin / therapeutic use
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Hypercholesterolemia / epidemiology,  physiopathology
Hypertension / complications,  physiopathology
Male
Microfilament Proteins / metabolism
Phosphoproteins / metabolism
Platelet Aggregation Inhibitors / administration & dosage,  therapeutic use*
Renal Insufficiency / complications,  physiopathology
Sex Factors
Smoking* / adverse effects
Ticlopidine / administration & dosage,  analogs & derivatives*,  therapeutic use
Treatment Outcome
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Microfilament Proteins; 0/Phosphoproteins; 0/Platelet Aggregation Inhibitors; 0/vasodilator-stimulated phosphoprotein; 50-78-2/Aspirin; 55142-85-3/Ticlopidine; 9005-49-6/Heparin; 90055-48-4/clopidogrel

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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