Factors influencing clopidogrel efficacy in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention: statin's advantage and the smoking "paradox"
Language English Country United States Media print
Document type Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
- MeSH
- Aspirin therapeutic use MeSH
- Angioplasty, Balloon, Coronary * MeSH
- Diabetes Mellitus, Type 2 complications physiopathology MeSH
- Phosphoproteins metabolism MeSH
- Heparin therapeutic use MeSH
- Hypercholesterolemia epidemiology physiopathology MeSH
- Hypertension complications physiopathology MeSH
- Body Mass Index MeSH
- Platelet Aggregation Inhibitors administration & dosage therapeutic use MeSH
- Clopidogrel MeSH
- Drug Therapy, Combination MeSH
- Coronary Angiography MeSH
- Smoking * adverse effects MeSH
- Humans MeSH
- Microfilament Proteins metabolism MeSH
- Cell Adhesion Molecules metabolism MeSH
- Coronary Artery Disease complications diagnostic imaging drug therapy therapy MeSH
- Renal Insufficiency complications physiopathology MeSH
- Aged MeSH
- Sex Factors MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use MeSH
- Ticlopidine administration & dosage analogs & derivatives therapeutic use MeSH
- Age Factors MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Aspirin MeSH
- Phosphoproteins MeSH
- Heparin MeSH
- Platelet Aggregation Inhibitors MeSH
- Clopidogrel MeSH
- Microfilament Proteins MeSH
- Cell Adhesion Molecules MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH
- Ticlopidine MeSH
- Vasodilator-Stimulated Phosphoprotein MeSH
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.
References provided by Crossref.org
Improving outcomes in patients undergoing percutaneous coronary intervention: role of prasugrel
