Ticagrelor Increases Adenosine Plasma Concentration in Patients With an Acute Coronary Syndrome

Objectives This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients. Background Ticagrelor is a direct-acting P2Y(12)-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non-platelet-directed properties. Animal and in vitro models suggested that the "pleiotropic" properties of ticagrelor may be related to an interaction with adenosine metabolism. Methods We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y(12)-adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index. Results Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 mu M [interquartile range: 0.98 to 1.7 mu M] vs. 0.68 mu M [interquartile range: 0.49 to 0.78 mu M]; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant). Conclusions Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells. (C) 2014 by the American College of Cardiology Foundation