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Thromb Haemost 2017; 117(05): 940-947
DOI: 10.1160/TH16-09-0703
Cellular Haemostasis and Platelets
Schattauer GmbH

Consistent platelet inhibition with ticagrelor 60 mg twice-daily following myocardial infarction regardless of diabetes status

Mark R. Thomas
1   Cardiovascular Research Unit, Department of Infection Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
,
Dominick J. Angiolillo
2   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
,
Marc P. Bonaca
3   TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
,
Ramzi A. Ajjan
4   Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
,
Heather M. Judge
1   Cardiovascular Research Unit, Department of Infection Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
,
Fabiana Rollini
2   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
,
Francesco Franchi
2   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA
,
Arif J. Ahsan
5   Trent Cardiac Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
,
Deepak L. Bhatt
3   TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
,
Julia F. Kuder
3   TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
,
Philippe Gabriel Steg
6   INSERM-Unité 1148, Assistance Publique- Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, and Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France
,
Marc Cohen
7   Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark, New Jersey, USA
,
Rangasamy Muthusamy
8   Rotherham NHS Foundation Trust, Rotherham, UK
,
Marc S. Sabatine
3   TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
,
Robert F. Storey
1   Cardiovascular Research Unit, Department of Infection Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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Publikationsverlauf

Received: 13. September 2016

Accepted after major revision: 09. Februar 2017

Publikationsdatum:
28. November 2017 (online)

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Summary

Diabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 ?M: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.

Keywords

Coronary artery disease - acute coronary syndromes - pharmacology - pharmacodynamics

 

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