Efficacy of ticagrelor compared to clopidogrel in improving endothelial function in patients with coronary artery disease: a systematic review

Abstract

BackgroundTicagrelor and clopidogrel are antiplatelet drugs that act by binding to the adenosine diphosphate P2Y12 receptor. Previous studies have compared between them regarding the endothelial function effect.ObjectivesThis systematic review aims to summarize the evidence comparing the efficacy of ticagrelor vs. clopidogrel in improving endothelial function in patients with coronary artery disease (CAD).MethodsIn August 2021, the Scopus, PubMed, Web of Science, and Cochrane library were searched systematically for eligible trials. We included randomized controlled trials that compared the efficacy of ticagrelor vs. clopidogrel in improving endothelial function in patients with CAD.ResultsSeven trials (n = 511) were included in our systematic review. Ticagrelor resulted in a greater elevation of the level of progenitor cells CD34+ KDR+ and CD34+ 133+ (P = 0.036 and P = 0.019, respectively), with a lower rate of endothelial cell apoptosis rate (P < 0.001). Moreover, ticagrelor showed superiority regarding nitric oxide, radical oxygen species, and soluble P-selectin levels (P = 0.03, P = 0.02, and P = 0.019, respectively). Flow-mediated dilation findings differed between the studies (P = 0.004 vs. P = 0.39).ConclusionTicagrelor appears to exert an additional improvement in endothelial function compared with clopidogrel in patients with coronary heart disease.

‘All roads lead to Rome’: the long journey of ticagrelor effect on endothelial function

“…However, the findings of ticagrelor on FMD are not consistent. Ticagrelor was shown to improve FMD compared with clopidogrel after just 1-month treatment in the article by Ariotti et al 8 On the contrary, no significant effect was found in the article by Schnorbus et al 9 Anyway, as shown by Albadrani et al , 6 the large majority of biomarkers support the effect of ticagrelor on endothelial function, and we may assume the existence of a positive modulation with potential clinical benefit.…”

“…6,7 On the other hand, ticagrelor was not significantly related to significant changes in reactive hyperemia index (RHI) and some biomarkers including circulating endothelial cells (CEC), white blood cells/CEC (WBC/CEC), WBC/endothelial progenitor cell (WBC/EPC) levels, endothelin-1, and soluble CD40 ligand. 6 Finally, results for flow-mediated dilatation (FMD) and EPC levels were conflicting. 6,8 The results of this systematic review raise two important questions: What is the global effect of ticagrelor on endothelial function considering that we have discordant results between different tests?…”

“…Between them, the authors found that after 1-month treatment, ticagrelor was associated with a significant reduction in apoptosis rates, higher nitric oxide (NO) levels, lower radical oxygen species (ROS) levels, and P selectin levels compared with clopidogrel 6,7 . On the other hand, ticagrelor was not significantly related to significant changes in reactive hyperemia index (RHI) and some biomarkers including circulating endothelial cells (CEC), white blood cells/CEC (WBC/CEC), WBC/endothelial progenitor cell (WBC/EPC) levels, endothelin-1, and soluble CD40 ligand 6 . Finally, results for flow-mediated dilatation (FMD) and EPC levels were conflicting 6,8 .…”

“…In the present issue of Journal of Cardiovascular Medicine , Albadrani et al 6 present a systematic review of the literature, summarizing the results of all randomized controlled trials aiming to compare ticagrelor and clopidogrel in the improvement of endothelial dysfunction in patients with coronary artery disease (CAD). The authors considered as valid tests for the evaluation of endothelial function 15 different methods.…”

“…6 Finally, results for flow-mediated dilatation (FMD) and EPC levels were conflicting. 6,8 The results of this systematic review raise two important questions: What is the global effect of ticagrelor on endothelial function considering that we have discordant results between different tests? Why is it important to understand if ticagrelor has pleiotropic effects that go beyond inhibition on P2Y12 inhibition?…”