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  •  Rivaroxaban and Risk of Venous Thromboembolism in Patients with Symptomatic Peripheral Artery Disease After Lower Extremity Revascularisation

Rivaroxaban and Risk of Venous Thromboembolism in Patients with Symptomatic Peripheral Artery Disease After Lower Extremity Revascularisation

Key Messages:

  • Peripheral artery disease (PAD) has previously been shown to confer elevated risk of arterial thrombotic complications, myocardial infarction (MI), stroke and amputation. Greater risk of venous thromboembolism (VTE) in stable PAD has also been demonstrated but the risk of VTE post lower extremity revascularisation (LER) is less determined
  • This study aimed to establish the risks of VTE following LER and if the use of low-dose rivaroxaban plus antiplatelet therapy is associated post LER VTE risk
  • The findings suggest that patients who underwent LER for PAD were at risk for VTE in addition to arterial thrombotic events, and low-dose rivaroxaban plus aspirin should be considered for reduction of the full spectrum of thrombotic risk

Study Design:

This cohort study was a secondary analysis of The Vascular Outcomes Study of ASA (acetylsalicylic acid) and Rivaroxaban in Endovascular or Surgical Limb Revascularisation for PAD (VOYAGER PAD), a double-blind randomised clinical trial. Data for this cohort were from VOYAGER PAD (NCT02504216).

Secondary endpoint:

  • Symptomatic VTE

Inclusion criteria:

  • Symptomatic PAD patients aged ≥50 years who underwent successful LER for claudication or critical limb ischemia via endovascular (including hybrid) or surgical approach
  • Key exclusion criteria included planned dual antiplatelet therapy for more than 6 months, need for systemic anticoagulation, recent acute limb ischemia or acute coronary syndrome, increased risk of bleeding, significantly impaired baseline kidney function, and prior intracranial hemorrhage, stroke, or transient ischemic attack


  • Total of 6,564 patients from 542 sites in 34 countries (66 patients had at least 1 VTE)
  • Independent risk factors identified: older age (hazard ratio [HR], 1.81; 95% confidence interval CI], 1.063.11), weight (HR, 3.04; 95% CI, 1.098.43), and hypertension (HR, 2.11; 95% CI, 0.914.89). Prior amputation (HR, 2.07; 95% CI, 0.954.53), an indicator of PAD severity, was also associated with VTE risk
  • VTE was associated with significantly increased risk of all-cause death during follow-up (HR, 7.22; 95% CI, 4.66-11.19), even after adjusting for VTE risk factors
  • Rivaroxaban was associated with a 39% lower risk of VTE (HR, 0.61; 95% CI, 0.370.998; p=0.047)
  • Event rates at 3 years of 1.7% in antiplatelet therapy alone vs 0.8% in those receiving rivaroxaban in addition to antiplatelet therapy


Patients with symptomatic PAD undergoing LER were at heightened risk of VTE. The risk of VTE is related to patient and PAD characteristics and was associated with poor prognosis. Rivaroxaban plus aspirin was associated with lower risk of VTE after LER, indicating broad thrombotic benefits of this approach.


  • VTE was investigator reported and used a secondary end point in VOYAGER PAD
  • Adjusted models did not factor in post randomisation variables
  • Associated factors were modeled, but formal predictive modeling was not performed
  • There was a low number of VTE events
  • The median time to death after VTE is likely due in part to fatal and nonfatal VTE events
  • The p value of <0.05 for rivaroxaban effect on VTE should be considered nominal