Total Ischemic Event Reduction With Rivaroxaban After Peripheral Arterial Revascularization in the VOYAGER PAD Trial

Abstract

Background: Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events. The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population is unknown.

Objectives: This study sought to evaluate the total burden of vascular events in patients with PAD after LER and the efficacy of low-dose rivaroxaban on total events.

Methods: VOYAGER PAD randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone. The primary endpoint was time to first event of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The current analysis considered all events (first and subsequent) for components of the primary endpoint as well as additional vascular events including peripheral revascularizations and venous thromboembolism. HRs were estimated by marginal proportional hazards models.

Results: Among 6,564 randomized events, there were 4,714 total first and subsequent vascular events including 1,614 primary endpoint events and 3,100 other vascular events. Rivaroxaban reduced total primary endpoint events (HR: 0.86; 95% CI: 0.75-0.98; P = 0.02) and total vascular events (HR: 0.86; 95% CI: 0.79-0.95; P = 0.003). An estimated 4.4 primary and 12.5 vascular events per 100 participants were avoided with rivaroxaban over 3 years.

Conclusions: Patients with symptomatic PAD who are undergoing LER have a high total event burden that is significantly reduced with rivaroxaban. Total event reduction may be a useful metric to quantify the efficacy of rivaroxaban in this setting. (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities [VOYAGER PAD]; NCT02504216).

Keywords: acute limb ischemia; peripheral artery disease; revascularization; rivaroxaban.

Conflict of interest statement

Funding Support and Author Disclosures The VOYAGER PAD trial was funded through a grant to CPC Clinical Research from Bayer and Janssen. Dr Bauersachs has received grant support from Aspen Pharma; and has received personal fees from Bayer, Bristol Myers Squibb, Daichii-Sankyo, and Pfizer. Dr Szarek has received fees for performing analyses, steering committee fees, and travel support from Sanofi and Regeneron; has received fees for performing analyses from Lexicon; has received consulting fees from CiVi and Esperion; and has received Data Safety and Monitoring Board membership fees from Resverlogix and Janssen. Dr Broadman has received grant support from Bayer. Dr Gudz has received grant support from Bayer AG. Dr Debus has received grants and personal fees from Bayer AG; and has received grants from Cook Ltd and Terumo Aortic, during the conduct of the study. Dr Nehler has received grant support to Brigham and Women’s Hospital from AstraZeneca and Merck; and grant support to CPC from Amgen, Anthos, AstraZeneca, Bayer, Janssen, Novo Nordisk, Sanofi, and WraSer. Dr Anand has received grant support from Bayer and Janssen. Dr Patel has received grant support from Bayer and Janssen. Dr Hess has received grant support to CPC from Amgen, Anthos, AstraZeneca, Bayer, Janssen, Novo Nordisk, Sanofi, and WraSer. Dr Capell has received grant support to CPC from Amgen, Anthos, AstraZeneca, Bayer, Janssen, Novo Nordisk, Sanofi, and WraSer. Dr Rogers has served as an adjudication committee member for VOYAGER; has received a small educational grant from Philipps; and has served as site co-principal investigator for trial sponsored by Abbott. Dr Muehlhofer has been employed by Bayer AG. Dr Haskell has been employed by Janssen. Dr Berkowitz was employed by Bayer as a clinical research physician at the time of this writing. Dr Hiatt has received grant support to CPC from Amgen, Anthos, AstraZeneca, Bayer, Janssen, Novo Nordisk, Sanofi, and WraSer. Dr Bonaca was supported by the American Heart Association Strategically Focused Research Network in Vascular Disease under awards 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (Brigham and Women’s Hospital-Dartmouth Hitchcock Clinical Project); has received grant support to BWH from AstraZeneca and Merck; and has received grant support to CPC from Amgen, Anthos, AstraZeneca, Bayer, Janssen, Novo Nordisk, Sanofi, and WraSer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Heart Association.

Copyright © 2021. Published by Elsevier Inc.