Thromb Haemost
DOI: 10.1055/s-0039-1695772
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Effects of Edoxaban on the Cellular and Protein Phase of Coagulation in Patients with Coronary Artery Disease on Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Results of the EDOX-APT Study

Francesco Franchi*
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Fabiana Rollini*
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Emilio Garcia
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Jose Rivas Rios
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Andrea Rivas
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Malhar Agarwal
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Megha Kureti
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Deepa Nagaraju
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Mustafa Wali
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Maryuri Briceno
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Jae Youn Moon
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Victor Kairouz
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Dmitry Yaranov
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Latonya Been
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Siva Suryadevara
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Daniel Soffer
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Martin M. Zenni
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Theodore A. Bass
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
,
Dominick J. Angiolillo
1  University of Florida College of Medicine–Jacksonville, Jacksonville, Florida, United States
› Author Affiliations
Funding This work was supported by an investigator-initiated study grant funded by Daiichi Sankyo. Thromboelastography cartridges specific for the assessment of nonvitamin-K oral anticoagulants were donated by Haemonetics.
Further Information

Publication History

04 June 2019

26 July 2019

Publication Date:
30 August 2019 (eFirst)

Abstract

In patients requiring dual antiplatelet therapy (DAPT) who also have an indication to be treated with oral anticoagulant (OAC) drugs, aspirin withdrawal reduces the risk of bleeding. There is limited data on the pharmacodynamic effects associated with adding a nonvitamin K antagonist OAC on a background of aspirin and a P2Y12 inhibitor as well as dropping aspirin. Seventy-five patients on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60 mg once daily, Group A), DAPT plus low-dose edoxaban (30 mg once daily, Group B), or DAPT only (Group C) for 10 ± 2 days (Phase I). Afterwards, Groups A and B interrupted aspirin and maintained clopidogrel plus edoxaban for 10 ± 2 days, while patients in Group C maintained DAPT (Phase II). Platelet aggregation and clot kinetics were assessed at baseline, end of Phase I, and end of Phase II using thrombelastography (TEG), light transmittance aggregometry (LTA), VerifyNow P2Y12, and serum thromboxane-B2. The primary endpoint was the comparison of maximum amplitude (MA) measured by TEG, a measure of clot strength, between patients on DAPT plus high-dose edoxaban and patients on DAPT only. Edoxaban prolonged in a dose-dependent manner speed of thrombin generation (TEG R; Group A: 7.7 [6.8–8.7] vs. Group B: 7.4 [6.4–8.5] vs. Group C: 6.3 [5.7–7.0]; p = 0.05) but did not affect other markers of clot kinetics, including TEG MA (Group A: 63 [61–64] vs. Group B: 65 [63–67] vs. Group C: 64 [63–65]; p = 0.10). After aspirin discontinuation, platelet reactivity assessed by LTA using thrombin receptor activating peptide as agonist increased to a greater extent with low-dose edoxaban. Stopping aspirin did not affect markers of P2Y12 reactivity and had no or marginal effects on clot kinetics, but increased markers sensitive to cyclooxygenase-1 blockade.

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* The first two authors contributed equally to this work.


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