Effect of caffeine on platelet inhibition by clopidogrel in healthy subjects and patients with coronary artery disease - 15/08/11
Résumé |
Background |
Clopidogrel inhibits the platelet P2Y12 receptor, leading to increased intracellular cyclic AMP (cAMP) levels. Caffeine also causes a rise in platelet cAMP. We aimed to test the effect of acute caffeine administration on platelet inhibition by clopidogrel, in healthy volunteers and patients with coronary artery disease.
Methods |
Cohort 1: 12 healthy subjects were enrolled in a 2-week crossover study. Blood samples were drawn at baseline, 2, 4, and 24 hours after 300 mg clopidogrel intake. At the first week, 6 subjects received caffeine (300 mg pill, equivalent to a medium sized coffee drink) 30 minutes after clopidogrel. At week 2, the other 6 subjects received caffeine. One month later the effect of caffeine alone was tested. Platelet function was evaluated by aggregation in response to 5, 10, and 20 μmol/L adenosine diphosphate, 1 μg/mL collagen, and flow cytometric determination of P-selectin expression, PAC-1 binding, and vasodilator-stimulated phosphoprotein phosphorylation. Cohort 2: 40 patients with coronary artery disease receiving aspirin and clopidogrel (75 mg daily) for ≥1 week were tested at baseline and 2.5 hours after caffeine (300 mg).
Results |
In cohort 1 (crossover study), caffeine was associated with lower adenosine diphosphate–induced aggregation at 4 hours, lower activation markers at 2 hours, and lower vasodilator-stimulated phosphoprotein phosphorylation at 4 hours after clopidogrel. Caffeine alone had no effect on the assessed platelet surface biomarkers. In cohort 2, caffeine administration was associated with lower platelet activation markers (P-selectin, PAC-1 binding), without significant effect on aggregation.
Conclusions |
Acute caffeine administration after clopidogrel loading appears to be associated with enhanced platelet inhibition 2 to 4 hours after clopidogrel intake. The mechanism probably involves synergistic increase in cAMP levels.
Le texte complet de cet article est disponible en PDF.Plan
Vol 154 - N° 4
P. 694.e1-694.e7 - octobre 2007 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?