CC BY-NC-ND 4.0 · Thromb Haemost 2017; 117(06): 1208-1216
DOI: 10.1160/TH16-12-0973
Atherosclerosis and Ischaemic Disease
Schattauer GmbH

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

Gianluca Campo
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
2  Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Center, Ferrara, Italy
,
Francesco Vieceli Dalla Sega
2  Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Center, Ferrara, Italy
3  Department of Medical Sciences, University of Ferrara, Ferrara, Italy
,
Rita Pavasini
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Giorgio Aquila
2  Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Center, Ferrara, Italy
3  Department of Medical Sciences, University of Ferrara, Ferrara, Italy
,
Francesco Gallo
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Francesca Fortini
2  Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Center, Ferrara, Italy
3  Department of Medical Sciences, University of Ferrara, Ferrara, Italy
,
Elisabetta Tonet
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Paolo Cimaglia
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Annamaria Del Franco
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Gabriele Pestelli
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Alessandro Pecoraro
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Marco Contoli
4  Research Centre on Asthma and COPD, Section of Internal and Cardio-Respiratory Medicine, University of Ferrara, Ferrara, Italy
,
Cristina Balla
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Simone Biscaglia
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
,
Paola Rizzo
5  Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
,
Roberto Ferrari
1  Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, Cona (FE), Italy
2  Laboratorio per le Tecnologie delle Terapie Avanzate (LTTA) Center, Ferrara, Italy
6  Maria Cecilia Hospital, GVM Care & Research, E. S.: Health Science Foundation, Cotignola, Italy
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Financial support: This study was partially supported by a research grant [ESR-14–10659] from AstraZeneca, which had no role in the collection, analysis, and interpretation of data; writing of the report; and the decision to submit the paper for publication.
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Publikationsverlauf

Received: 30. Dezember 2016

Accepted after major revision: 08. März 2017

Publikationsdatum:
07. November 2017 (online)

  

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 P2Y12 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.