학술논문
Platelet P2Y12 inhibiting therapy in adjunct to vascular dose of rivaroxaban or aspirin: a pharmacodynamic study of dual pathway inhibition vs. dual antiplatelet therapy.
Document Type
Academic Journal
Author
Galli M; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy.; Franchi F; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Rollini F; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Been L; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Jaoude PA; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Rivas A; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Zhou X; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Jia S; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Maaliki N; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Lee CH; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Pineda AM; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Suryadevara S; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Soffer D; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Zenni MM; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Geisler T; Department of Cardiology and Angiology, University of Tübingen, Tübingen, Germany.; Jennings LK; MLM Medical Labs, LLC, Memphis, TN, USA.; Bass TA; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.; Angiolillo DJ; Division of Cardiology, University of Florida College of Medicine, 655 West 8th Street, Jacksonville, FL 32209, USA.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 101669491 Publication Model: Print Cited Medium: Internet ISSN: 2055-6845 (Electronic) NLM ISO Abbreviation: Eur Heart J Cardiovasc Pharmacother Subsets: MEDLINE
Subject
Language
English
Abstract
Aims: Dual pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data on a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) are limited.
Methods and Results: This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study. We analysed data from 40 patients treated with either clopidogrel- or ticagrelor-based DAPT first, and clopidogrel- or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of (1) P2Y12 reactivity, (2) platelet-mediated global thrombogenicity, (3) cyclooxygenase-1 activity, (4) thrombin receptor-activating peptide (TRAP)-induced platelet aggregation, (5) tissue factor (TF)-induced platelet aggregation, and (6) thrombin generation. Compared with DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation, and no differences in markers of P2Y12 signalling, platelet-mediated global thrombogenicity, and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signalling, and rates of high platelet reactivity compared with clopidogrel.
Conclusion: Compared with DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations.
Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03718429.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Methods and Results: This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study. We analysed data from 40 patients treated with either clopidogrel- or ticagrelor-based DAPT first, and clopidogrel- or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of (1) P2Y12 reactivity, (2) platelet-mediated global thrombogenicity, (3) cyclooxygenase-1 activity, (4) thrombin receptor-activating peptide (TRAP)-induced platelet aggregation, (5) tissue factor (TF)-induced platelet aggregation, and (6) thrombin generation. Compared with DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation, and no differences in markers of P2Y12 signalling, platelet-mediated global thrombogenicity, and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signalling, and rates of high platelet reactivity compared with clopidogrel.
Conclusion: Compared with DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations.
Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03718429.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)