Department of Clinical and Molecular Medicine, Institution of Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
J Am Coll Cardiol. 2013 Feb 19;61(7):723-7. doi: 10.1016/j.jacc.2012.11.032. Epub 2013 Jan 9.
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 P2Y(12) 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).
本研究旨在确定替格瑞洛是否可增强人类受试者中腺苷诱导的冠脉血流和呼吸困难感觉。
替格瑞洛是一种 P2Y(12)受体拮抗剂，在 III 期试验（PLATO [血小板抑制和患者结局]）中与氯吡格雷相比显示出更好的临床获益。在犬模型中，替格瑞洛已被证明可抑制细胞摄取腺苷并增强腺苷介导的充血反应。
在这项双盲、安慰剂对照研究中，40 名健康男性受试者以交叉方式随机接受单次剂量的替格瑞洛（180mg）或安慰剂。在研究药物之前和之后进行多次逐步腺苷输注，并在输注茶碱后，通过经胸多普勒超声心动图测量静息时的冠脉血流速度（CBFV）。
与安慰剂相比，替格瑞洛显著增加了 CBFV 与腺苷剂量的曲线下面积（p = 0.008）。替格瑞洛血浆浓度与曲线下面积增加之间存在显著相关性（p < 0.001）。在两个治疗组中，茶碱均可显著减弱腺苷诱导的 CBFV 增加，而接受替格瑞洛或安慰剂的受试者之间无显著差异（p = 0.39）。此外，替格瑞洛显著增强了腺苷输注期间的呼吸困难感觉，而茶碱可减弱这种作用。
替格瑞洛通过一种腺苷介导的机制增强了这些健康男性受试者中腺苷诱导的 CBFV 和呼吸困难感觉。（替格瑞洛对健康男性受试者冠脉血流影响的评估研究；NCT01226602）。
