ticagrelor and Hyperemia

Topics: Aged; Coronary Artery Disease; Endothelium, Vascular; Female; Humans; Hyperemia; Male; Manometry; Microvessels; Middle Aged; Platelet Aggregation Inhibitors; Plethysmography; Ticagrelor; Vascular Stiffness

Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function.. We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation.. This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post-ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI <1.67.. We identified 30 eligible patients with endothelial function assessment pre- and post-ticagrelor cessation (86.7% men, 13.3% with diabetes and 33.3% current smokers; mean age: 63.6±11.5 years). The study's primary endpoint of RHI at Day 5 did not differ significantly compared with RHI at Day 0, 1.69 (1.45-2.23) vs 1.81 (1.59-2.13). ED rate did not differ significantly between Day 5 and Day 0, 40 vs 33.3%, p=0.8, respectively. No differences in RHI or ED rate were observed between Day 2 and Day 0, 1.64 (1.54-2.04) vs 1.8 1(1.59-2.13), p=0.3 and 53.3 vs 33.3%, p=0.2, respectively. In stable CAD patients there is no evidence of deterioration in endothelial function after discontinuing ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Drug Administration Schedule; Endothelium, Vascular; Evidence-Based Medicine; Female; Humans; Hyperemia; Male; Manometry; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Treatment Outcome; Vasodilation

A routine secondary pharmacology screen indicated that reversibly binding oral P2Y(12) receptor antagonist ticagrelor could inhibit adenosine uptake in human erythrocytes, suggesting that ticagrelor may potentiate adenosine-mediated responses in vivo. The aim of this study was to further characterize the adenosine uptake inhibition in vitro and study possible physiological consequences of adenosine uptake inhibition by ticagrelor in an anesthetized dog model of coronary blood flow compared to dipyridamole.. We measured [2-3H]adenosine uptake in purified human erythrocytes and several cell lines in the presence of ticagrelor or the known uptake inhibitor dipyridamole as a comparator. Using an open-chest dog model (beagles), we measured the left anterior descending (LAD) coronary artery blood flow during reactive hyperemia after 1 minute occlusion or intracoronary infusion of adenosine before and after administration of vehicle, ticagrelor, or dipyridamole (each n = 8). Ticagrelor concentration-dependently inhibited adenosine uptake in human erythrocytes and in cell lines of rat, canine, or human origin. In the dog model, ticagrelor and dipyridamole dose-dependently augmented reactive hyperemia after LAD occlusion, as assessed by percentage repayment of flow debt relative to control (both Ps < .05). Ticagrelor and dipyridamole also dose-dependently augmented intracoronary adenosine-induced increases in LAD blood flow relative to control (both Ps < .05).. Ticagrelor inhibits adenosine uptake in vitro and subsequently augments cardiac blood flow in a canine model of reactive hypoxia- or adenosine-induced blood flow increases. These findings suggest that ticagrelor may have additional benefits in patients with acute coronary syndrome beyond inhibition of platelet aggregation.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Cell Line; Cell Line, Tumor; Coronary Circulation; Dipyridamole; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Erythrocytes; Female; Humans; Hyperemia; Male; Purinergic P2Y Receptor Antagonists; Rats; Ticagrelor