TY - JOUR
T1 - Dual pathway inhibition in patients with atherosclerotic disease
T2 - pharmacodynamic considerations and clinical implications
AU - Galli, Mattia
AU - Franchi, Francesco
AU - Rollini, Fabiana
AU - Ortega-Paz, Luis
AU - D’Amario, Domenico
AU - De Caterina, Raffaele
AU - Mehran, Roxana
AU - Gibson, C. Michael
AU - Angiolillo, Dominick J.
N1 - Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - Introduction: The persistence of elevated rates of ischemic recurrences despite the use of antiplatelet therapy among patients with atherosclerotic disease together with the understanding of the pivotal role of coagulation in the thrombo-inflammatory processes involved in the pathogenesis of atherosclerosis and its complications has fostered the development of treatments targeting both platelets and coagulation, a strategy known as dual-pathway inhibition (DPI). Areas covered: In this review we discuss the recent advancements in the understanding of the interplay between coagulation, platelets and inflammation involved in the pathophysiology of atherosclerosis and atherothrombosis, as the rationale for the implementation of a DPI strategy. We also discuss the available pharmacodynamic (PD) evidence and clinical implications with the use of DPI in patients with atherosclerotic disease. Expert opinion: The implementation of a DPI by adding the so-called ‘vascular dose of rivaroxaban’ (i.e. 2.5 mg bis in die), on top of antiplatelet therapy has consistently been associated with reduced levels of thrombin generation in PD studies and with reduced ischemic event rates at the cost of increased bleeding compared to antiplatelet therapy alone. Further research is warranted to best define patients in whom a DPI regimen has the best safety and efficacy profile.
AB - Introduction: The persistence of elevated rates of ischemic recurrences despite the use of antiplatelet therapy among patients with atherosclerotic disease together with the understanding of the pivotal role of coagulation in the thrombo-inflammatory processes involved in the pathogenesis of atherosclerosis and its complications has fostered the development of treatments targeting both platelets and coagulation, a strategy known as dual-pathway inhibition (DPI). Areas covered: In this review we discuss the recent advancements in the understanding of the interplay between coagulation, platelets and inflammation involved in the pathophysiology of atherosclerosis and atherothrombosis, as the rationale for the implementation of a DPI strategy. We also discuss the available pharmacodynamic (PD) evidence and clinical implications with the use of DPI in patients with atherosclerotic disease. Expert opinion: The implementation of a DPI by adding the so-called ‘vascular dose of rivaroxaban’ (i.e. 2.5 mg bis in die), on top of antiplatelet therapy has consistently been associated with reduced levels of thrombin generation in PD studies and with reduced ischemic event rates at the cost of increased bleeding compared to antiplatelet therapy alone. Further research is warranted to best define patients in whom a DPI regimen has the best safety and efficacy profile.
KW - Dual-pathway inhibition
KW - aspirin
KW - atherosclerotic disease
KW - clopidogrel
KW - dual antiplatelet therapy
KW - pharmacodynamic
KW - rivaroxaban
KW - ticagrelor
UR - http://www.scopus.com/inward/record.url?scp=85144129795&partnerID=8YFLogxK
U2 - 10.1080/17512433.2023.2154651
DO - 10.1080/17512433.2023.2154651
M3 - Article
C2 - 36455906
AN - SCOPUS:85144129795
SN - 1751-2433
VL - 16
SP - 27
EP - 38
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
IS - 1
ER -