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When should dual pathway inhibition be stopped in patients with symptomatic PAD following peripheral revascularization?

Patient case: 

  • Jack, aged 65 years, was diagnosed with peripheral artery disease (PAD). His symptoms did not improve with conservative treatments such as exercise therapy
  • Several months ago, Jack underwent lower-extremity revascularization to relieve his severe symptoms of leg pain. Since then, he has been taking dual pathway inhibition (DPI) with rivaroxaban vascular dose 2.5 mg twice daily (bid) plus low-dose aspirin to reduce his risk of vascular events
  • The procedure was successful and has improved his symptoms, allowing him to complete simple tasks around the house again
  • Jack has tolerated DPI therapy well, with no major bleeding events or contraindications, and has not experienced any vascular events. At a follow-up visit, he asks his physician when he should stop DPI therapy
When should DPI therapy be stopped in patients like Jack?

When should DPI therapy be stopped in patients like Jack?

The risk of ischaemic events increases after lower-extremity revascularization and persists over time

Patients with symptomatic PAD already have a heightened risk of ischaemic events, with an almost twofold greater risk of cardiovascular (CV) death than those without PAD, and those with critical limb ischaemia have a 20% risk of limb loss at 1 year.1,2 In Jack’s situation, as in many other patients, lower-extremity revascularization was required to improve symptoms of pain and walking discomfort.3,4 However, the risk of CV and limb events, such as major amputation or another peripheral revascularization, is even higher in patients who have undergone lower-extremity revascularization and persists over time. In particular, the risk of limb events is highest immediately following a peripheral revascularization procedure, whereas the risk of CV events, such as myocardial infarction (MI) or stroke, increases steadily over time.4

MALE, major adverse limb events; MI, myocardial infarction

Patients who undergo lower-extremity revascularization face a long-term risk of vascular events4

Dual pathway inhibition can reduce the risk of ischaemic events after revascularization and over the long term

So when should Jack stop DPI? Extra protection is critical for patients such as Jack to prevent life-threatening CV events and to preserve limbs in the years following a peripheral revascularization procedure. The latest evidence supports the use of DPI immediately after establishing haemostasis following revascularization, as well as the long-term continuation of DPI into the chronic phase in the absence of contraindications.5-7


DPI, dual pathway inhibition

The VOYAGER PAD and COMPASS studies support the continued use of DPI for vascular protection after lower-extremity revascularization in eligible patients5-7

The European Society of Vascular Medicine (ESVM), European Society of Cardiology (ESC) and Global Vascular Guidelines (GVG) guidelines recognize that patients with PAD may benefit from antithrombotic therapy following revascularization. However, the recommended antithrombotic regimens and duration vary, reflecting the lack of robust evidence available on the most appropriate regimen in this setting.3,8,9


The phase III VOYAGER PAD study is the only large, randomized study to demonstrate a clinically relevant benefit of antithrombotic treatment for patients with symptomatic PAD undergoing lower-extremity revascularization. In this study, patients with PAD were initiated on DPI with rivaroxaban 2.5 mg bid plus low-dose aspirin or low-dose aspirin within 10 days following a successful revascularization procedure. DPI significantly lowered the combined risk of limb ischaemia and major CV events by 15% compared with aspirin, with no significant increase in the risk of the primary safety endpoint of Thrombolysis In Myocardial Infarction major bleeding.5


The results of the VOYAGER PAD study complement the observations of the COMPASS study, which showed that in the subgroup of patients with chronic PAD, DPI significantly reduced the combination of CV death, MI or stroke by 28%, and reduced major adverse limb events (MALE) and major amputation by 46%, versus aspirin alone. Despite the increase in modified International Society on Thrombosis and Haemostasis major bleeding with DPI therapy, there was no significant increase in the most serious types of bleeding compared with aspirin alone.6

ALI, acute limb ischaemia; bid; twice daily; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; PAD, peripheral artery disease; RRR, relative risk reduction

DPI reduced the risk of limb ischaemia and major CV events compared with aspirin in patients with symptomatic PAD following peripheral revascularization and in the chronic phase5,6

Based on the COMPASS study results, the ESVM and GVG guidelines now recommend considering DPI in patients with chronic PAD without a high risk of bleeding events or other contraindications as part of an overall vascular protection strategy.3,9 The ESC chronic coronary syndrome guidelines include recommendations for considering DPI in patients with coronary artery disease and PAD.10 These guidelines were released before the completion of VOYAGER PAD. Together, the VOYAGER PAD and COMPASS studies demonstrate the consistent efficacy and safety profile of DPI across the continuum of PAD, from patients with symptomatic PAD requiring revascularization to the chronic phase.5,6



Even if symptoms improve after lower-extremity revascularization, patients remain at high risk of limb ischaemia and vascular events, both immediately after the procedure and in the long term. The VOYAGER PAD study results support the use of DPI immediately after establishing haemostasis following revascularization, whereas the COMPASS study supports the long-term continuation of DPI into the chronic phase in the absence of contraindications. Long-term DPI therapy could help patients like Jack to remain independent and to continue life with the knowledge that they are protected from life-threatening vascular events and limb ischaemia.


As Professor Sebastian Debus explains in the video below: ‘Since this [VOYAGER PAD] is the first large randomized trial focused exclusively on this subgroup of patients, we now have high evidence for this benefit in our patients. So, our patients should receive this treatment [DPI] shortly after intervention and operation, which then should be extrapolated according to the COMPASS regimen, which means a life-long treatment for those patients, which will be affected with a marked reduction of MACE and MALE events’.

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