Low-Dose Rivaroxaban Plus Aspirin in Fragile Patients After Lower Extremity Revascularization.

Background: Rivaroxaban 2.5 mg plus aspirin reduced limb and cardiovascular events and increased bleeding in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization in 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) study. Fragile patients are at heightened risk for ischemic and bleeding events.
Objectives: The purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD.
Methods: Patients were categorized as fragile based on prespecified criteria (age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m ² ). The primary efficacy outcome was the composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding.
Results: Of 6,564 randomized patients, a total of 1,674 subjects were categorized as fragile at baseline. In the placebo arm, fragile patients were at higher risk of the primary outcome (HR: 1.34; 95% CI: 1.12-1.61) and TIMI major bleeding (HR: 1.57; 95% CI: 0.83-2.96), compared with nonfragile patients. The effect of rivaroxaban on the primary endpoint was not modified by frailty status (fragile HR: 0.93; 95% CI: 0.75-1.15; nonfragile HR: 0.83; 95% CI: 0.72-0.97; P interaction = 0.37). Rivaroxaban increased TIMI major bleeding in fragile (HR: 1.54; 95% CI: 0.82-2.91) and nonfragile patients (HR: 1.37; 95% CI: 0.84-2.23; P interaction = 0.65).
Conclusions: Patients with PAD after lower extremity revascularization meeting fragile criteria are at higher risk of ischemic complications and bleeding. Rivaroxaban reduces ischemic risk and increases bleeding regardless of frailty status. These data may assist in personalization of antithrombotic therapy in fragile population.
Competing Interests: Funding Support and Author Disclosures VOYAGER PAD was funded by Bayer and Janssen Pharmaceuticals. The Colorado Prevention Center Clinical Research held the database and performed all analyses, and the decision to submit this manuscript for publication was made by the VOYAGER PAD Publications Committee. Drs Canonico, Low Wang, Hsia, Nehler, Capell, Berkowitz, and Bonaca receive salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2023 from the following organizations: Abbott Laboratories, Agios Pharmaceuticals, Inc, Alexion Pharma Godo Kaisha, Amgen Inc, Anthos Therapeutics, Inc, ARCA biopharma, Inc, AstraZeneca Pharma India, AstraZeneca Pharmaceuticals LP, AstraZeneca UK Ltd, AstraZeneca Produtos Farmaceuticos, Lda, Atentiv, LLC, Bayer, Bayer (Proprietary) Limited, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol Myers Squibb, CellResearch Corporation Pte Ltd, Cleerly, Inc, Colorado Department of Public Health and Environment, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc, EPG Communication Holdings Ltd, Esperion Therapeutics, Inc, Faraday Pharmaceuticals, Inc, HeartFlow Inc, Insmed, Ionis Pharmaceuticals, IQVIA Inc, Janssen Pharmaceuticals, Inc, Janssen Research and Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc, LSG Corporation, MedImmune Limited, Medpace, Inc, Medscape, Merck Sharp and Dohme Corp, Nectero Medical Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk, Osiris Therapeutics, Inc, Pfizer, PPD Development, LP, Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics SA, Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc, The Brigham and Women's Hospital, Inc, Thrombosis Research Institute, University of Colorado Denver, University of Pittsburgh, VarmX, and WraSer, LLC. Dr Hsia owns stock in AstraZeneca. Dr Debus has received grant support from Cook and Terumo Aortic. Dr Patel has received grant support, advisory board fees, and consulting fees from AstraZeneca, Bayer, and Janssen; has received grant support from Medtronic and Philips Healthcare; and has received grant support and advisory board fees from Heartflow. Dr Anand has received lecture fees from Bayer and Janssen. Dr Muehlhofer was employed by Bayer. Dr Haskell was employed by Janssen Pharmaceuticals; and has owned stock in Johnson and Johnson. Dr Berkowitz was employed by Bayer during the operationalization of the VOYAGER PAD study. Dr Bauersachs has received consulting fees and lecture fees from Bayer, Bristol Myers Squibb, and Pfizer. Dr Bonaca has received support from the AHA SFRN under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (BWH-DH Clinical Project); and has stock in Medtronic and Pfizer. Dr Ycas has reported that he has no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)