Mori J Krantz1,2, Sebastian E Debus3, Judith Hsia1, Manesh R Patel4, Sonia S Anand5, Mark R Nehler1,6, Connie N Hess1,2, Warren H Capell1,2, Taylor Bracken1, Michael Szarek1,7, Lajos Mátyás8, Dainis K Krievins9,10, Patrice Nault11, Stefan Stefanov12, Lloyd P Haskell13, Scott D Berkowitz14, Eva Muehlhofer15, William R Hiatt1,2, Rupert M Bauersachs16,17, Marc P Bonaca1,2. 1. CPC Clinical Research, 2115 N Scranton Street, Suite 2040, Aurora, CO, USA. 2. Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA. 3. Department of Vascular Medicine, Vascular Surgery-Angiology-Endovascular Therapy, University of Hamburg-Eppendorf, Hamburg, Germany. 4. Duke Clinical Research Institute, Division of Cardiology, Duke University, Durham, NC, USA. 5. Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada. 6. Department of Surgery, Division of Vascular Surgery, University of Colorado School of Medicine, Aurora, CO, USA. 7. SUNY Downstate Health Sciences University, 450 Clarkson Ave, Brooklyn, NY 11203, USA. 8. Borsod Central Teaching County Hospital. 9. University of Latvia, Latvia. 10. Pauls Stradins Clinical University Hospital, Vascular and Endovascular Surgery CISSSO, Gatineau, Québec, Canada. 11. McGill University, Canada. 12. City Clinic Cardiology Centre Multiprofile Hospital for Active Treatment EOOD. 13. Janssen Research and Development, Raritan, NJ, USA. 14. Thrombosis & Vascular Medicine, Clinical Development, Bayer U.S, Whippany, NJ, USA. 15. Bayer AG Research & Development, Pharmaceuticals, Wuppertal, Germany. 16. Department of Vascular Medicine, Klinikum Darmstadt, Darmstadt, Germany. 17. Center for Thrombosis and Hemostasis, University of Mainz, Mainz, Germany.
Abstract
AIMS: In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. METHODS AND RESULTS: The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). CONCLUSION: Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: In this secondary analysis of the VOYAGER trial, rivaroxaban 2.5 mg twice/day plus aspirin 100 mg/day was assessed in older adults. Advanced age is associated with elevated bleeding risk and unfavourable net benefit for dual antiplatelet therapy in chronic coronary artery disease. The risk-benefit of low-dose rivaroxaban in patients ≥75 years with peripheral artery disease (PAD) after lower extremity revascularization (LER) has not been described. METHODS AND RESULTS: The primary endpoint was a composite of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death. The principal safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding analysed by the pre-specified age cut-off of 75 years. Of 6564 patients randomized, 1330 (20%) were >75 years. Absolute 3-year Kaplan-Meier cumulative incidence rates for primary efficacy (23.4% vs. 19.0%) and safety (3.5% vs. 1.5%) endpoints were higher in elderly vs. non-elderly patients. Efficacy of rivaroxaban (P-interaction 0.83) and safety (P-interaction 0.38) was consistent irrespective of age. The combination of intracranial and fatal bleeding was not increased in patients >75 years (2 rivaroxaban vs. 8 placebo). Overall, benefits (absolute risk reduction 3.8%, number needed to treat 26 for the primary endpoint) exceeded risks (absolute risk increase 0.81%, number needed to harm 123 for TIMI major bleeding). CONCLUSION: Patients ≥75 years with PAD are at both heightened ischaemic and bleeding risk after LER. No excess harm with respect to major, intracranial or fatal bleeding was seen in older patients yet numerically greater absolute benefits were observed. This suggests that low-dose rivaroxaban combined with aspirin should be considered in PAD after LER regardless of age. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Connie N Hess; Michael Szarek; Sonia S Anand; Rupert M Bauersachs; Manesh R Patel; E Sebastian Debus; Mark R Nehler; Warren H Capell; Joshua A Beckman; Gregory Piazza; Stanislav Henkin; Alessandra Bura-Rivière; Holger Lawall; Karel Roztocil; Judith Hsia; Eva Muehlhofer; Scott D Berkowitz; Lloyd P Haskell; Marc P Bonaca Journal: JAMA Netw Open Date: 2022-06-01