![Randomization and Treatment
Eligible patients were randomly assigned in a 1:1 ratio
to receive rivaroxaban at a dose of 2.5 mg twice
daily or placebo was stratified according to the type
of index procedure (endovascular [including hybrid] vs
surgical) and according to clopidogrel use or nonuse
within the group of patients who underwent an
endovascular procedure
Neither the investigators nor the patients were aware
of the treatment assignments.
All patients were to receive aspirin at a dose of 100
mg daily as background therapy](https://image.slidesharecdn.com/voyagerpad-221106155856-72012c8c/85/voyager-pad-pptx-25-320.jpg)
![RESULTS
6564 patients underwent randomization
3286 were assigned to the rivaroxaban group, and 3278 were assigned
to the placebo group
The primary efficacy outcome occurred in 335 (10.3%) patients in the
rivaroxaban group and in 448 (13.8%) in the placebo group respectively
(hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P =
0.009)
TIMI major bleeding occurred in 62 patients in the rivaroxaban group
and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio,
1.43; 95% CI, 0.97 to 2.10; P = 0.07)
ISTH major bleeding occurred in 140 patients in the rivaroxaban group,
as compared with 100 patients in the placebo group (5.94% and 4.06%;
hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007)](https://image.slidesharecdn.com/voyagerpad-221106155856-72012c8c/85/voyager-pad-pptx-34-320.jpg)
voyager pad.pptx
- 1. - VOYAGER PAD Trial
- 3. BACKGROUND Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events The efficacy and safety of rivaroxaban in this context are uncertain
- 11. METHOD Double-blind trial Patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin
- 12. Primary efficacy outcome Acute limb ischemia Major amputation for vascular causes Myocardial infarction Ischemic stroke, or death from cardiovascular causes
- 15. Principal safety outcome Major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification Major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome
- 20. INCLUSION CRITERIA 50 years old Documented lower-extremity peripheral artery disease, including symptoms, anatomical evidence, and hemodynamic evidence Patients were eligible after a successful revascularization procedure performed within the previous 10 days for symptoms of peripheral artery disease
- 21. Anatomical Evidence Imaging evidence of peripheral artery disease distal to the external iliac artery in the index leg within 12 months prior or at time of qualifying Hemodynamic Evidence ABI ≤ 0.80 for patients without a prior history of limb revascularization, OR ABI ≤ 0.85 for patients with a prior history of limb revascularization
- 22. Definitions Critical Limb Ischemia (CLI)1: Patients with chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease Hemodynamics: Rest pain with ankle pressure 50 mm Hg or less and toe pressure 30 mm Hg or less Tissue loss (ulcer or gangrene) 70 mm Hg or less and toe pressure 50 mm Hg or less
- 24. EXCLUSION CRITERIA Patients undergoing revascularization for asymptomatic PAD or mild claudication without functional limitation of the index leg Acute limb ischemia (ALI) within 2 weeks prior to the qualifying revascularization Patients with major tissue loss (defined as significant ulceration/gangrene proximal to the metatarsal heads, i.e. heel or midfoot) in either leg Planned dual antiplatelet therapy (DAPT) use for the qualifying revascularization procedure of clopidogrel in addition to ASA for >6 months Clinically unstable Heightened risk for bleeding
- 25. Randomization and Treatment Eligible patients were randomly assigned in a 1:1 ratio to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo was stratified according to the type of index procedure (endovascular [including hybrid] vs surgical) and according to clopidogrel use or nonuse within the group of patients who underwent an endovascular procedure Neither the investigators nor the patients were aware of the treatment assignments. All patients were to receive aspirin at a dose of 100 mg daily as background therapy
- 26. Enrollment and Follow-up A total of 6564 patients underwent randomization from August 2015 through January 2018 The median follow-up period was 28 months A total of 6504 patients (99.1%) received at least one dose of trial medication Of these patients, 1080 (33.2%) in the rivaroxaban group and 1011 (31.1%) in the placebo group discontinued treatment prematurely
- 34. RESULTS 6564 patients underwent randomization 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group The primary efficacy outcome occurred in 335 (10.3%) patients in the rivaroxaban group and in 448 (13.8%) in the placebo group respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009) TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07) ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007)
- 39. DISCUSSION Patients with symptomatic peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events
- 40. In this trial, which involved a broad population of patients who had undergone lower-extremity revascularization, nearly 1 in 5 patients in the placebo group had the primary composite outcome The addition of rivaroxaban at a dose of 2.5 mg twice daily to aspirin reduced this risk by approximately 15%
- 41. There was no significant excess in the principal safety outcome of TIMI major bleeding with rivaroxaban There was a significantly higher incidence of the secondary safety outcome of ISTH major bleeding However, there was no excess in intracranial hemorrhage or fatal bleeding
- 42. CONCLUSIONS In patients with peripheral artery disease who had undergone lower-extremity revascularization Rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone