title: Effect of caffeine on platelet inhibition by clopidogrel in healthy subjects and patients with coronary artery disease.
abstract: 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 micromol/L adenosine diphosphate, 1 microg/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 > or = 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.
authors: The Methodist Hospital Research Institute and the Methodist DeBakey Heart Center, Houston, TX 77030, USA.
authors: Eli I
authors: EI
authors: Lev
authors: Mehmet E
authors: ME
authors: Arikan
authors: Muthiah
authors: M
authors: Vaduganathan
authors: Carlos L
authors: CL
authors: Alviar
authors: Armando
authors: A
authors: Tellez
authors: Nilesh
authors: N
authors: Mathuria
authors: Angela
authors: A
authors: Builes
authors: Juan F
authors: JF
authors: Granada
authors: Ian
authors: I
authors: del Conde
authors: Neal S
authors: NS
authors: Kleiman
mesh_terms: D000328:Adult; D000368:Aged; D002110:Caffeine / Q000494:pharmacology*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000503:physiopathology / Q000628:therapy; D018592:Cross-Over Studies; D004357:Drug Synergism; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C514579:(4-benzylpiperazin-1-yl)acetic acid (3-allyl-2-hydroxybenzylidene)hydrazine; D006835:Hydrazones; D019007:P-Selectin; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D043705:Receptor, Adenosine A2A; D002110:Caffeine; D000077144:Clopidogrel; D013988:Ticlopidine