Does Ticagrelor Improve Endothelial Function?

Abstract

Ticagrelor is a P2Y receptor antagonist with proven clinical benefit in patients with acute coronary syndrome. Apart from its principal antiplatelet action, pleiotropic effects have been implicated in the clinical profile of ticagrelor, including a potentially beneficial impact on endothelial function. In light of the common presence and prognostic value of endothelial dysfunction in patients with coronary artery disease, several clinical studies have investigated the postulated effect of ticagrelor on endothelial function, yielding conflicting results. Limitations of the relevant studies as well as substantial differences in patient population, study design, and methods may account for these controversial findings. Most of these studies, however, support a beneficial impact of ticagrelor on endothelial function, which seems to be significant in the higher risk patients. In order to elucidate this effect, further research efforts should aim to clarify how quickly does endothelial function respond to ticagrelor, how sustained this response is during the dosing intervals and in the long term, which mechanisms are implicated, and whether this pleiotropic action is clinically significant. Future studies should include larger and diverse populations of patients, assess endothelial function at several time points after treatment initiation, and use multiple methods of endothelial function measurement, while implementing strict methodology. Nevertheless, the extent of the clinical benefit of ticagrelor attributable to actions beyond its potent and consistent antiplatelet effect remains uncertain.

Ticagrelor Conditioning Effects Are Not Additive to Cardioprotection Induced by Direct NLRP3 Inflammasome Inhibition: Role of RISK, NLRP3, and Redox Cascades

“…Our study, in which the P2Y12 antagonist was administered in vivo and myocardial infarct subsequently induced ex vivo, in the absence of platelets, definitively confirms that the protective effect is mainly due to a preconditioning effect in vivo that lasts throughout the IR procedure ex vivo. The lack of cardioprotection by Ticagrelor when administered in the ex vivo model further support the idea of a blood cell-mediated preconditioning effect [5,8,31]. Given the apparent dependence upon the presence of blood in mediating Ticagrelor effects [5,17], it would seem logical to propose that the cardioprotective effect of Ticagrelor is dependent on platelets and likely the P2Y12 receptor.…”

“…Ticagrelor was dissolved at 3.70 μ M concentration in Krebs solution. The in vivo dose of Ticagrelor and the in vitro concentrations of both Ticagrelor and INF were chosen according to previous studies demonstrating their efficacy against myocardial IR injury [ 13 , 24 , 28 , 31 ].…”

Ticagrelor Does Not Improve Endothelial Dysfunction in Stable Survivors of Acute Coronary Syndrome

“…The biologic effects of adenosine on ameliorating endothelial dysfunction are well established. 4,9,24 In addition, ticagrelor was found to block the contractile effect of adenosine diphosphate in the vascular smooth muscle that expresses P2Y 12 receptors. 25 In humans, a loading dose of ticagrelor 180 mg increased the plasma adenosine concentration in patients with ACS compared to a loading dose of clopidogrel 600 mg. 5 A loading dose of ticagrelor 180 mg also enhanced adenosine-induced coronary blood flow velocity in healthy volunteers 6 and in patients with NSTE-ACS.…”

“…[16][17][18] Peripheral arterial tonometry and baFMD provide distinct information regarding vascular function, and baFMD is the most established and commonly used method, although baFMD is more technically difficult. 9,19 However, until now, only 2 prior studies have evaluated the effect of ticagrelor on endothelial dysfunction using baFMD. One study evaluated patients with stable CAD but did not enroll patients with prior ACS, 11 while the other enrolled patients with ACS with type 2 diabetes in the acute period.…”

“…[4][5][6][7][8] Mechanisms potentially related to the improvement in endothelial function have been proposed. 4,9 While a series of clinical trials investigated the effect of ticagrelor on endothelial function in patients with coronary artery disease (CAD), the results were contradictory. [10][11][12][13][14][15][16][17][18] Probable explanations of these inconsistent findings include different clinical presentations, comorbidities, methods to evaluate endothelial function, timing from the index event, and the various statuses of concomitant medications.…”