Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial function, inflammatory parameters, and platelet function in patients with acute coronary syndrome undergoing coronary artery stenting: a randomized, blinded, parallel study

Aim In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 629years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P=0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P<0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68-3.58; P=0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31-2.83; P=0.0155), but this difference was limited to patients who received the study therapy 2h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI -0.73 to 1.82; P=0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P=0.02 and P=0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P=0.002 and P=0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusions As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73