Does Ticagrelor Improve Endothelial Function?

J Cardiovasc Pharmacol Ther. 2019 Jan;24(1):11-17. doi: 10.1177/1074248418786936. Epub 2018 Jul 10.

Abstract

Ticagrelor is a P2Y12 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.

Keywords: flow-mediated dilation; pleiotropic action; reactive hyperemia index; ticagrelor.

Publication types

  • Review

MeSH terms

  • Animals
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / physiopathology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Hemodynamics / drug effects*
  • Humans
  • Peripheral Arterial Disease / drug therapy*
  • Peripheral Arterial Disease / metabolism
  • Peripheral Arterial Disease / physiopathology
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Receptors, Purinergic P2Y12 / drug effects*
  • Receptors, Purinergic P2Y12 / metabolism
  • Signal Transduction
  • Ticagrelor / adverse effects
  • Ticagrelor / therapeutic use*

Substances

  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Ticagrelor