Biological effects of ticagrelor over clopidogrel in patients with stable coronary artery disease and chronic obstructive pulmonary disease

Abstract

Summary Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3% vs 9.3 ± 1.5%, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y 12 reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608). Supplementary Material to this article is available online at www.thrombosis-online.com.

Ticagrelor mitigates ischaemia–reperfusion induced vascular endothelial dysfunction in healthy young males – a randomized, single‐blinded study

“…However, Campo et al . reported increased NO and mitigated ROS levels during ticagrelor treatment, which also induced higher adenosine plasma concentrations in cardiac patients .…”

“…We cannot conclude if ticagrelor's limited benefit is due to exceeding its capacity of NO synthase stimulation with subsequent imbalance of NO and ROS as these parameter were not assessed. However, Campo et al reported increased NO and mitigated ROS levels during ticagrelor treatment, which also induced higher adenosine plasma concentrations in cardiac patients [34,37].…”

Endothelial dysfunction and increased platelet reactivity in patients with acute coronary syndrome and undiagnosed COPD: insights into the SCAP trial

“…A previous study on ACS patients showed that treatment with ticagrelor was able to improve endothelial function (tested with peripheral arterial tonometry) [10]. This was confirmed in a randomised clinical trial of COPD patients with stable coronary artery disease [6]. The present analysis confirms, in the subset of patients with UCOPD and ACS, this pleiotropic effect of ticagrelor on endothelial dysfunction, similarly for the relationship between ticagrelor and on-treatment platelet reactivity in UCOPD patients.…”

“…Blood sample was obtained from an antecubital vein using a 21-gauge needle. The specific analyses for the present study were: 1) endothelial dysfunction assay, assessed by the rate of apoptosis in human umbilical vein endothelial cells (HUVECs) after 48-h incubation with 20% serum from patients, as previously reported [5,6]; 2) on-treatment platelet reactivity measured with light transmittance aggregometry after arachidonic acid and adenosine diphosphate stimulus [7]. Continuous data were tested for normal distribution with the Kolmogorov-Smirnov test.Normally distributed values were presented as mean±SD and compared by t-test and one-way ANOVA.…”

Systematic review with meta‐analysis: the risk of gastrointestinal bleeding in patients taking third‐generation P2Y12 inhibitors compared with clopidogrel

“…A total of 80 potential eligible studies were then reviewed for full‐text evaluations, of which 39 articles were excluded because they did not meet the inclusion criteria (Table S1). Finally, 41 RCTs were included in the meta‐analysis with 23 trials comparing ticagrelor with clopidogrel and 18 trials comparing prasugrel with clopidogrel, in which bleeding data from ClinicalTrial.gov were used for the study of Ge 2010 . The selection steps and specific excluding reasons were shown in Figure .…”