Ticagrelor Enhances Adenosine-Induced Coronary Vasodilatory Responses in Humans

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• 作者：Ann Wittfeldt ; MD^? ; H&aring ; kan Emanuelsson ; MD ; PhD^&dagger ; ; Gunnar Brandrup-Wognsen ; MD ; PhD^? ; ^&dagger ; ; J.J.J. van Giezen ; PhD^&dagger ; ; Jenny Jonasson ; PhD^&dagger ; ; Sven Nylander ; PhD^&dagger ; ; Li-Ming Gan ; MD ; PhD^? ; ^&dagger ; ; ^{li-ming.gan@astrazeneca.com}
• 关键词：adenosine ; coronary blood flow ; dyspnea ; ticagrelor
• 刊名：Journal of the American College of Cardiology
• 出版年：2013
• 出版时间：19 February, 2013
• 年：2013
• 卷：61
• 期：7
• 页码：723-727
• 全文大小：1136 K

文摘

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Objectives

This study was undertaken to determine if ticagrelor augments adenosine-induced coronary blood flow and the sensation of dyspnea in human subjects.

Background

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.

Methods

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.

Results

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.

Conclusions

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; )