Ticagrelor Enhances Adenosine-Induced Coronary Vasodilatory Responses in Humans

• Published in: Journal of the American College of Cardiology Vol. 61; no. 7; pp. 723 - 727
• Main Authors: Wittfeldt, Ann, Emanuelsson, Håkan, Brandrup-Wognsen, Gunnar, van Giezen, J.J.J., Jonasson, Jenny, Nylander, Sven, Gan, Li-Ming
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 19.02.2013; Elsevier; Elsevier Limited
• Subjects: Acute coronary syndromes; acute myocardial-infarction; adenosine; Adenosine - analogs & derivatives; Adenosine - pharmacology; adjunct; Adolescent; Adult; Biological and medical sciences; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Cardiology; Cardiology and Cardiovascular Disease; Cardiology. Vascular system; Cardiovascular; clopidogrel; Confidence intervals; coronary blood flow; Coronary heart disease; Coronary Vessels - drug effects; Coronary Vessels - physiology; Cross-Over Studies; Double-Blind Method; Drug Synergism; Drug therapy; dyspnea; Flow velocity; Heart; Heart attacks; Humans; Kardiologi och kardiovaskulära sjukdomar; Male; Medical sciences; multicenter; Physiology; Purinergic P2Y Receptor Antagonists - pharmacology; ticagrelor; trial; Up-Regulation - drug effects; Up-Regulation - physiology; Variance analysis; Vasodilation - drug effects; Vasodilation - physiology; Young Adult; Sweden; adenosine; CBFV; CV; CI; dyspnea; ticagrelor; coronary blood flow; LAD; AUC; left anterior descending coronary artery; area under the curve; confidence interval; coronary blood flow velocity; coefficient of variation; Human; Purine nucleoside; Adenosine; Coronary artery; Cardiovascular disease; Coronary heart disease; Antiplatelet agent; Vasodilation; Response; Vasomotricity; Circulatory system; Cardiology; Ticagrelor
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2012.11.032

This study was undertaken to determine if ticagrelor augments adenosine-induced coronary blood flow and the sensation of dyspnea in human subjects. Ticagrelor is a P2Y12 receptor antagonist that showed superior clinical benefit versus clopidogrel in a phase III trial (PLATO [Platelet Inhibition and Patient Outcomes]). Ticagrelor has been shown to inhibit cell uptake of adenosine and enhance adenosine-mediated hyperemia responses in a dog model. In this double-blind, placebo-controlled study, 40 healthy male subjects were randomized to receive a single dose of ticagrelor (180 mg) or placebo in a crossover fashion. Coronary blood flow velocity (CBFV) was measured by using transthoracic Doppler echocardiography at rest after multiple stepwise adenosine infusions given before and after study drug, and again after the infusion of theophylline. Ticagrelor significantly increased the area under the curve of CBFV versus the adenosine dose compared with placebo (p = 0.008). There was a significant correlation between ticagrelor plasma concentrations and increases in the area under the curve (p < 0.001). In both treatment groups, the adenosine-induced increase in CBFV was significantly attenuated by theophylline, with no significant differences between subjects receiving ticagrelor or placebo (p = 0.39). Furthermore, ticagrelor significantly enhanced the sensation of dyspnea during adenosine infusion, and the effects were diminished by theophylline. Ticagrelor enhanced adenosine-induced CBFV and the sensation of dyspnea in these healthy male subjects via an adenosine-mediated mechanism. (Study to Assess the Effect of Ticagrelor on Coronary Blood Flow in Healthy Male Subjects; NCT01226602)