Thromb Haemost 2020; 120(08): 1147-1158
DOI: 10.1055/s-0040-1713376
Review Article

Dual Pathway Inhibition for Vascular Protection in Patients with Atherosclerotic Disease: Rationale and Review of the Evidence

Jeffrey Ian Weitz
1  Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada
Dominick J. Angiolillo
2  Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States
Tobias Geisler
3  Department of Cardiology and Angiology, University Hospital Tübingen, Tübingen, Germany
Stefan Heitmeier
4  Research and Development Pharmaceuticals, Bayer AG, Wuppertal, Germany
› Author Affiliations
Funding Writing support was provided by Chameleon Communications International, Ltd, with funding from Bayer AG.


Despite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease.


The authors were fully responsible for the content of the paper and made the decision to submit the manuscript. J.I.W. holds the Canada Research Chair in Thrombosis and the Heart and Stroke Foundation J. Fraser Mustard Chair in Cardiovascular Research.

Publication History

Received: 30 October 2019

Accepted: 08 May 2020

Publication Date:
28 June 2020 (online)

Georg Thieme Verlag KG
Stuttgart · New York