SLR - December 2021 - Laura B. Adler
Reference: Hiatt, W. R., Bonaca, M. P., Patel, M. R., Nehler, M. R., Debus, E. S., Anand, S. S., Capell, W. H., Brackin, T., Jaeger, N., Hess, C. N., Pap, A. F., Berkowitz, S. D., Muehlhofer, E., Haskell, L., Brasil, D., Madaric, J., Sillesen, H., Szalay, D., & Bauersachs, R. (2020). Rivaroxaban and Aspirin in Peripheral Artery Disease Lower Extremity Revascularization: Impact of Concomitant Clopidogrel on Efficacy and Safety. Circulation, 142(23), 2219–2230. https://doi.org/10.1161/circulationaha.120.050465Level of Evidence: I
Scientific Literature Review
Reviewed By: Laura B. Adler, DPM
Residency Program: Presbyterian St. Luke’s Medical Center – Denver, CO
Podiatric Relevance: The purpose of this article was to assess the efficacy and safety of rivaroxaban when used in conjunction with clopidogrel following lower extremity revascularization. This study contains information that may be useful for podiatrists taking care of patients undergoing revascularization as well as understanding our patient’s anticoagulation therapy going forward. This study sought to answer whether clopidogrel alters the efficacy or safety profile of rivaroxaban.
Methods: Data and methods were from the VOYAGER PAD trial (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), a randomized, double-blind, placebo-controlled phase 3 study.
Inclusion criteria: 6,564 subjects randomized in 34 countries who had symptomatic PAD, defined by ABI <0.8 or TBI <0.6 in either limb with occlusive disease affecting circulation distal to the external iliac artery. Subjects were randomized who had technically successful endovascular, hybrid, or surgical lower extremity revascularization within 10 days and had hemostasis before randomization.
Exclusion criteria: Patients were excluded if they had planned long-term dual antiplatelet therapy (>6 months), a requirement for therapeutic anticoagulation, recent acute limb ischemia or acute coronary syndrome, conditions that could increase the risk of major bleeding, significantly impaired kidney function at baseline and any history of intracranial hemorrhage, stroke, or transient ischemic attack.
Patients were randomized 1:1 to receive either rivaroxaban + aspirin or rivaroxaban-placebo + aspirin. Clopidogrel use was allowed at the discretion of the provider. The primary efficacy outcome was a composite of events including ALI, major amputation due to vascular issue, MI, ischemic stroke, or cardiovascular death.
Results: Rivaroxaban resulted in an early decrease in acute limb ischemia within 30 days.
Rivaroxaban increased thrombolysis in myocardial infarction, similarly to aspirin, regardless of clopidogrel use. With concomitant use of clopidogrel >30 days, rivaroxaban was associated with more major bleeding within one year compared with shorter durations of clopidogrel use, which was statistically significant.
Conclusions: This study supports adding rivaroxaban to aspirin following lower extremity revascularization regardless of concomitant clopidogrel use. Because there was a trend towards more major bleeding with clopidogrel, a shorter course (=30 days) may be associated with decreased bleeding.