"Potential Effect of Acute and Chronic Caffeine Administration on Platelet Reactivity in Patient With Coronary Artery Disease on Dual Antiplatelet Therapy"

Prasugrel is a potent thienopyridine antiplatelet agent that selectively and irreversibly inhibits ADP-induced platelet aggregation mediated by the P2Y12 receptor. Prasugrel is a prodrug that must first undergo biotransformation to its active metabolite via cytochrome P450-mediated hepatic metabolism (CYP1A2). Clopidogrel is currently administered to several million patients especially after coronary stenting. Clopidogrel has been shown to reduce cardiovascular complications in patients with acute coronary syndromes and patients who have undergone coronary stenting. The mechanism of action of clopidogrel's active metabolite involves inhibition of the purinergic adenosine diphosphate (ADP) receptor P2Y12 on the platelet membrane. Blockade of this receptor prevents uncoupling of the associated Gi2 protein which ultimately leads to increased platelet cyclic AMP (cAMP) formation.3 Cyclic AMP is a key signaling molecule in inhibiting platelet aggregation, but its intracellular levels are affected by several other commonly used compounds. For instance, methylxanthines, such as caffeine, theophylline, and theobromine (an ingredient of chocolate), all cause elevation of intracellular cAMP levels by inhibiting adenosine receptors (types A1 and A2) on the platelet membrane. The effect of caffeine consumption on platelet reactivity depends on the caffeine dose and duration of administration. Chronic caffeine consumption (≥7 days) appears to be associated with inhibition of platelet aggregation, probably through upregulation of adenosine receptors. The effect of acute caffeine administration on platelet function is less clear. Different studies have shown either an increase, decrease, or no change in platelet reactivity after acute caffeine administration. The aim of this study was to examine the effect of acute caffeine consumption, at a dose equivalent to commercial coffee drinks, on the antiplatelet effect of clopidogrel and prasugrel, in patients with coronary artery disease (CAD).

Platelet function will be evaluated using a validated method: the VerifyNow System (Accumetrics Inc., San Diego, CA), which is a point-of-care turbidimetry-based optical detection system that measures platelet-induced aggregation. Platelet function will be measured with the VerifyNow P2Y12 test at baseline, (after 5 day wash-out period to avoid any carryover effect ) and after 10 days of taking caffeine.