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

• Published in: Journal of the American College of Cardiology Vol. 84; no. 9; pp. 801 - 811
• Main Authors: Canonico, Mario Enrico, MD, PhD, Low Wang, Cecilia C., MD, Hsia, Judith, MD, Debus, E. Sebastian, MD, PhD, Nehler, Mark R., MD, Patel, Manesh R., MD, Anand, Sonia S., MD, Ycas, Joseph, PhD, Capell, Warren H., MD, Muehlhofer, Eva, MD, Haskell, Lloyd P., MD, MBA, Berkowitz, Scott D., MD, Bauersachs, Rupert, MD, Bonaca, Marc P., MD, MPH
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.08.2024
• Subjects: Aged; Aged, 80 and over; Aspirin - administration & dosage; Aspirin - therapeutic use; Cardiovascular; Double-Blind Method; Drug Therapy, Combination; Factor Xa Inhibitors - administration & dosage; Factor Xa Inhibitors - therapeutic use; Female; fragile patients; Frailty; Humans; Lower Extremity - blood supply; Lower Extremity - surgery; MACE; MALE; Middle Aged; Peripheral Arterial Disease - surgery; peripheral artery disease; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; Postoperative Complications - etiology; Postoperative Complications - prevention & control; rivaroxaban; Rivaroxaban - administration & dosage; Rivaroxaban - therapeutic use; Vascular Surgical Procedures; chronic kidney disease; fragile patients; peripheral artery disease; lower extremity revascularization; rivaroxaban; MALE; acute limb ischemia; PAD; MACE; major adverse limb events; LER; major adverse cardiovascular events; CKD; ALI
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2024.05.060

AbstractBackgroundRivaroxaban 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. ObjectivesThe purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD. MethodsPatients 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. ResultsOf 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). ConclusionsPatients 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.