Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel

Francesco Franchi; Fabiana Rollini; Jung Rae Cho; Rhodri King; Fladia Phoenix; Mona Bhatti; Christopher DeGroat; Antonio Tello-Montoliu; Martin M. Zenni; Luis A. Guzman; Theodore A. Bass; Ramzi A. Ajjan; Dominick J. Angiolillo

doi:10.1160/th15-06-0467

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2016; 115(03): 622-631
DOI: 10.1160/th15-06-0467

Cellular Haemostasis and Platelets

Schattauer GmbH

Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel

Results from a prospective, randomised, double-blind, placebo-controlled study

Francesco Franchi

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Fabiana Rollini

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Jung Rae Cho

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Rhodri King

²Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

,

Fladia Phoenix

²Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

,

Mona Bhatti

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Christopher DeGroat

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Antonio Tello-Montoliu

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Martin M. Zenni

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Luis A. Guzman

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Theodore A. Bass

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

,

Ramzi A. Ajjan

²Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

,

Dominick J. Angiolillo

¹University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA

› Institutsangaben

Abstract

Summary

There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y₁₂ receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

Keywords

Antithrombin - platelet pharmacology - pharmacodynamics - thrombosis

Volltext

Referenzen

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