Effect of caffeine on platelet inhibition by clopidogrel in healthy subjects and patients with coronary artery disease

Thienopyridine-Associated Drug-Drug Interactions: Pharmacologic Mechanisms and Clinical Relevance

“…In a crossover study, acute caffeine administration after clopidogrel loading was associated with enhanced platelet inhibition 2 to 4 h after clopidogrel intake [33]. Coadministration of medications that increase platelet cAMP levels (eg, the phosphodiesterase inhibitor cilostazol) has been proposed to decrease the proportion of clopidogrel nonresponders [34].…”

Design and rationale of TROCADERO: A TRial Of Caffeine to Alleviate DyspnEa Related to ticagrelOr

“…21,22 Chronic caffeine administration is associated with an increase in adenosine A2A receptors 23,24 and enhances platelet inhibition obtained from a clopidogrel loading dose. 25 Caffeine-containing beverages are widely consumed worldwide. Thus, several epidemiological and observational studies have been performed with regard to safety of this compound.…”

The colonic metabolites dihydrocaffeic acid and dihydroferulic acid are more effective inhibitors of in vitro platelet activation than their phenolic precursors

“…Previous studies have evaluated the effect of 300 -600 mg orally administered caffeine on human platelet function. 53,54 These studies showed that only when caffeine was administered after clopidogrel treatment (a typical treatment as part of coronary stenting), enhanced platelet inhibition could be observed, whilst caffeine itself had no significant effect on ADP-and collagen-induced platelet aggregation or activation in caffeinetreated subjects compared with a placebo group. However, caffeine significantly decreased in vitro ADP-induced P-selectin expression at equivalent plasma concentrations, yet, the effect may be small.…”

“…68,69 Previous studies have demonstrated that polyphenols, such as caffeic acid, quercetin or epigallocatechin-3-gallate, act through this mechanism. 70,71,72 Methylxanthines also have been associated with an increase of cAMP levels due to up-regulation of platelet Gs protein-coupled adenosine 2A receptor, 53,54 which mediates the production of cAMP by adenylyl cyclase in platelets. 73 Moreover it has recently been demonstrated that chlorogenic acid presents an active site to the adenosine 2A receptor, favoring the increase of cAMP levels and therefore an inhibition of platelet activation.…”