Rupert M Bauersachs1, Michael Szarek2, Marianne Brodmann3, Ivan Gudz4, Eike Sebastian Debus5, Mark R Nehler6, Sonia S Anand7, Manesh R Patel8, Connie N Hess9, Warren H Capell10, Kevin Rogers9, Eva Muehlhofer11, Lloyd P Haskell12, Scott D Berkowitz13, William R Hiatt14, Marc P Bonaca15. 1. CCB-Cardiovascular Center Bethanien, Frankfurt, Germany; Center for Thrombosis and Hemostasis, University of Mainz, Mainz, Germany. 2. CPC Clinical Research, Aurora, Colorado, USA; Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA; SUNY Downstate Health Sciences University, Brooklyn, New York, USA. 3. Division of Angiology, Medical University of Graz, Graz, Austria. 4. Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine. 5. Department of Vascular Medicine, Vascular Surgery-Angiology-Endovascular Therapy, University of Hamburg-Eppendorf, Hamburg, Germany. 6. Department of Surgery, Division of Vascular Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA. 7. Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada. 8. Duke Clinical Research Institute, Division of Cardiology, Duke University, Durham, North Carolina, USA. 9. Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA. 10. Department of Medicine, Division of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, USA. 11. Bayer AG Research and Development, Pharmaceuticals, Wuppertal, Germany. 12. Janssen Research and Development, Raritan, New Jersey, USA. 13. Thrombosis and Vascular Medicine, Clinical Development, Bayer US, Whippany, New Jersey, USA. 14. CPC Clinical Research, Aurora, Colorado, USA; Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA. 15. CPC Clinical Research, Aurora, Colorado, USA; Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA. Electronic address: marc.bonaca@cpcmed.org.
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).
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).
Authors: Michael Szarek; Connie Hess; Manesh R Patel; W Schuyler Jones; Jeffrey S Berger; Iris Baumgartner; Brian Katona; Kenneth W Mahaffey; Lars Norgren; Juuso Blomster; Frank W Rockhold; Judith Hsia; F Gerry R Fowkes; Marc P Bonaca Journal: J Am Heart Assoc Date: 2022-05-27 Impact factor: 6.106
Authors: Scott D Berkowitz; Rupert M Bauersachs; Michael Szarek; Mark R Nehler; E Sebastian Debus; Manesh R Patel; Sonia S Anand; Warren H Capell; Connie N Hess; Judy Hsia; Nicholas J Leeper; David Brasil; Lajos Mátyás; Rafael Diaz; Marianne Brodmann; Eva Muehlhofer; Lloyd P Haskell; Marc P Bonaca Journal: J Thromb Haemost Date: 2022-03-07 Impact factor: 16.036