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Abstract
Advances in antiplatelet therapies for patients with cardiovascular disease have improved patient outcomes over time, but the challenge of balancing the risks of ischaemia and bleeding remains substantial. Moreover, many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. Therefore, novel strategies are needed to prevent clinical events through mechanisms beyond platelet inhibition and with an acceptable associated risk of bleeding. The advent of non-vitamin K antagonist oral anticoagulants, which attenuate fibrin formation by selective inhibition of factor Xa or thrombin, has renewed the interest in dual-pathway inhibition strategies that combine an antiplatelet agent with an anticoagulant drug. In this Review, we highlight the emerging pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with different manifestations of cardiovascular disease, such as coronary artery disease, cerebrovascular disease and peripheral artery disease.
Many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. In this Review, Angiolillo and colleagues discuss the pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with cardiovascular disease.
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; Eikelboom, John W 3 ; Fox Keith A A 4
; Geisler, Tobias 5 ; Gibson, Michael, C 6
; Gonzalez-Juanatey, Jose Ramon 7 ; James, Stefan 8 ; Lopes, Renato D 9 ; Mehran Roxana 10 ; Montalescot Gilles 11 ; Patel, Manesh 9 ; Gabriel, Steg P 12 ; Storey, Robert F 13 ; Vranckx Pascal 14 ; Weitz, Jeffrey I 15 ; Welsh, Robert 16 ; Zeymer Uwe 17 ; Angiolillo, Dominick J 18
1 Azienda Ospedaliero-Universitaria ‘Policlinico-Vittorio Emanuele’, University of Catania, Division of Cardiology, C.A.S.T., P.O. ‘G. Rodolico’, Catania, Italy (GRID:grid.8158.4) (ISNI:0000 0004 1757 1969)
2 Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
3 Population Health Research Institute, Hamilton General Hospital and McMaster University, Hamilton, Canada (GRID:grid.415102.3) (ISNI:0000 0004 0545 1978)
4 University of Edinburgh, Centre for Cardiovascular Science, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988)
5 University Hospital of Tübingen, Department of Cardiology and Angiology, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249)
6 Beth Israel Deaconess Medical, Harvard Medical School, Cardiovascular Division, Department of Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
7 University Hospital, IDIS, CIBERCV, Cardiology Department, Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
8 Uppsala University, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457)
9 Duke University, Division of Cardiology, Duke Clinical Research Institute, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
10 Icahn School of Medicine at Mount Sinai, Cardiovascular Institute, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
11 Sorbonne Université, ACTION Study Group, Institut de Cardiologie, Pitié Salpêtrière Hôpital (AP-HP), Paris, France (GRID:grid.462844.8) (ISNI:0000 0001 2308 1657)
12 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris University, FACT (French Alliance for Cardiovascular Trials), INSERM U1148, Paris, France (GRID:grid.26009.3d)
13 University of Sheffield, Department of Infection, Immunity and Cardiovascular Disease, Sheffield, UK (GRID:grid.11835.3e) (ISNI:0000 0004 1936 9262)
14 Hartcentrum Hasselt, and Faculty of Medicine and Life Sciences at the University of Hasselt, Department of Cardiology and Critical Care Medicine, Hasselt, Belgium (GRID:grid.487153.c)
15 McMaster University and the Thrombosis and Atherosclerosis Research Institute, Departments of Medicine and Biochemistry and Biomedical Sciences, Hamilton, Canada (GRID:grid.418562.c)
16 Mazankowski Alberta Heart Institute and University of Alberta, Cardiac Sciences Department, Edmonton, Canada (GRID:grid.418562.c)
17 Klinikum Ludwigshafen and Institut für Herzinfarktforschung, Ludwigshafen, Germany (GRID:grid.488379.9) (ISNI:0000 0004 0402 5184)
18 University of Florida College of Medicine, Division of Cardiology, Jacksonville, USA (GRID:grid.413116.0) (ISNI:0000 0004 0625 1409)