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Testing Acetylcholine Followed by Adenosine for Invasive Diagnosis of Coronary Vasomotor Disorders
Published on: February 3, 2021
Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans
Ann Wittfeldt1, Håkan Emanuelsson, Gunnar Brandrup-Wognsen
1Department of Clinical and Molecular Medicine, Institution of Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Insights
Ticagrelor, a P2Y(12) receptor antagonist, was found to increase coronary blood flow and the sensation of dyspnea in healthy subjects. These effects were mediated by adenosine and could be diminished by theophylline.
Area of Science:
- Cardiovascular Pharmacology
- Human Physiology
Background:
- Ticagrelor is a P2Y(12) receptor antagonist with demonstrated clinical benefits.
- Preclinical studies in dogs suggest ticagrelor enhances adenosine-mediated hyperemia.
Purpose of the Study:
- To investigate if ticagrelor augments adenosine-induced coronary blood flow (CBFV) and dyspnea in humans.
- To explore the role of adenosine in ticagrelor's effects on CBFV and dyspnea.
Main Methods:
- A double-blind, placebo-controlled, crossover study involving 40 healthy males.
- Measurement of CBFV using transthoracic Doppler echocardiography during adenosine infusions.
- Administration of ticagrelor or placebo, followed by theophylline to assess adenosine mediation.
Main Results:
- Ticagrelor significantly increased the area under the curve of CBFV in response to adenosine compared to placebo.
- Ticagrelor enhanced the sensation of dyspnea during adenosine infusion.
- Theophylline attenuated adenosine-induced CBFV increases in both ticagrelor and placebo groups, indicating an adenosine-mediated mechanism.
Conclusions:
- Ticagrelor enhances adenosine-induced coronary blood flow and dyspnea in healthy subjects.
- The observed effects are mediated through an adenosine-dependent pathway.
- Findings suggest ticagrelor's interaction with adenosine pathways may influence cardiovascular and respiratory responses.
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 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.
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; NCT01226602).
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