Can the risk of vascular events be reduced in patients with peripheral artery disease undergoing lower-extremity endovascular revascularization?

Patient case

Alex recently turned 69 years of age. After retiring from his career as a solicitor’s clerk, he finally found the time to pursue his lifelong passion of pottery
Alex suffered from leg pain stemming from peripheral artery disease (PAD) for many years
However, despite following his physician’s advice and persevering with exercise therapy, Alex’s leg pain got worse. The pain became so bad that Alex had to rely on his nephew for getting groceries and the daily newspaper
Because Alex’s leg pain interfered significantly with his daily life, his physician suggested revascularization to try and improve his leg symptoms
Magnetic resonance angiography revealed short stenosis in the femoral artery. Based on the length and location of the lesion, the physician decided on endovascular revascularization
His physician told Alex that his antithrombotic therapy would need to be intensified after the procedure, because Alex’s risk of vascular events would be increased after revascularization

The revascularization was successful. Alex will be discharged from hospital soon, but the risk of vascular events continues to worry him. What are the antithrombotic options after lower-extremity endovascular revascularization, and when can the treatment be started?

The risk of major adverse vascular events after revascularization is high1

Patients with symptomatic PAD, like Alex, often suffer from leg pain that starts while walking and may cause the patient to stop and rest. For some, rest will not help to clear the symptoms; for others, the pain may start at rest.2 In some cases, these leg symptoms can prevent the patient from walking at a fast pace, walking long distances or climbing stairs, leading to loss of mobility and disruption of their daily activities.3

The 2019 European Society of Vascular Medicine (ESVM) guidelines, the 2019 Global Vascular Guidelines (GVG) and the 2017 European Society of Cardiology (ESC) guidelines on PAD recommend non-interventional approaches, such as exercise therapy and analgesia, for patients with symptomatic PAD to reduce the burden of symptoms.4-6 However, sometimes the quality of life in patients with PAD suffering from claudication is severely impaired even with exercise therapy and other conservative treatments. In these cases, the guidelines recommend revascularization as an option to relieve the symptomatic burden.4,5

Peripheral revascularization can be achieved either by surgery or by endovascular interventions, such as balloon angioplasty or stenting.7 Several revascularization techniques are available to bypass or remove the atherosclerotic occlusion, or open the occluded artery, and restore blood flow to the limb to alleviate the symptoms of intermittent claudication.4,7 Endovascular revascularization is recommended for short lesions and when the surgical risk is elevated.5 Revascularization, particularly in combination with exercise therapy, has been shown to increase walking ability in patients with symptomatic PAD.8,9

Endovascular revascularization might improve the symptoms of PAD, but is Alex right to worry about his increased risk of vascular events?

About 1 in 15 patients who undergo endovascular revascularization for the relief of symptomatic PAD will have an unplanned readmission to hospital, and almost 1 in 30 will need a lower-limb vascular reintervention or amputation within 30 days of the index procedure.10,11

After a median follow-up of 2.7 years, around 1 in 17 patients who undergo revascularization will be hospitalized for myocardial infarction or stroke, and around 1 in 3 will experience repeat revascularization or major amputation.1

The risk of major vascular events after revascularization for symptom relief in symptomatic PAD is high1,10,11

When can intensified antithrombotic therapy be initiated after peripheral revascularization?

The clinical practice guideline recommendations on intensified antithrombotic therapy after peripheral revascularization vary.4-6 The 2017 ESC, 2019 ESVM and 2019 GVG guidelines recommend considering dual antiplatelet therapy (DAPT) for at least 1 month after peripheral endovascular interventions, but the 2019 ESVM guidelines also recommend DAPT for at least 3 months after implantation of drug-eluting or covered stents, and the 2019 GVG recommend considering DAPT for 1–6 months in patients undergoing repeated catheter-based interventions if they are at low risk of bleeding.4-6 Additionally, there is a lack of robust evidence to support these recommendations, which are often inferred from clinical studies in the setting of coronary revascularization.4-6,12

VOYAGER PAD is the only large randomized study to demonstrate a clinically relevant benefit of antithrombotic treatment for patients with symptomatic PAD undergoing lower-extremity revascularization. The regimen assessed in this trial was dual pathway inhibition (DPI) with rivaroxaban vascular dose 2.5 mg twice daily (bid) plus low-dose aspirin versus aspirin.13

The primary composite efficacy outcome of acute limb ischaemia, major amputation of vascular aetiology, myocardial infarction, ischaemic stroke or cardiovascular death was significantly reduced by 15% with DPI compared with aspirin, and the primary safety outcome of Thrombolysis In Myocardial Infarction (TIMI) major bleeding was not statistically significantly increased.13 Patients undergoing various types of endovascular and surgical revascularization procedures were included in the study. Furthermore, there was no heterogeneity for the safety and efficacy outcomes between major subgroups, including those based on age, sex, cardiovascular risk factors or type of intervention.13

The results of the VOYAGER PAD trial complement the results of the COMPASS trial. The COMPASS trial results showed that DPI significantly reduced the combination of cardiovascular death, myocardial infarction and stroke in patients with chronic coronary artery disease and/or PAD compared with aspirin. The risk of major bleeding events was increased versus aspirin alone, but there was no significant increase in the most serious types of bleeding.14,15 Taken together, the results from the VOYAGER PAD and COMPASS trials demonstrate consistent protection with DPI across the continuum in PAD, from post-revascularization to the chronic phase.13,15

How long after revascularization was DPI initiated in the VOYAGER PAD trial and what does this mean for patients like Alex? Patients in the VOYAGER PAD trial were initiated on DPI treatment within 10 days after the qualifying technically successful revascularization and after haemostasis was established. A revascularization procedure was considered successful if there was no immediate plan for reintervention, patency was demonstrated and the investigator deemed it safe to initiate antithrombotic therapy.13 Therefore, the results of the VOYAGER PAD trial suggest that DPI can be initiated immediately after successful peripheral revascularization and establishing haemostasis, based on the treating physician’s clinical judgment and the local label recommendations.13

The results of the VOYAGER PAD trial suggest that DPI can be initiated immediately after successful peripheral revascularization and establishing haemostasis in eligible patients13,15

Summary

The results of VOYAGER PAD suggest that rivaroxaban vascular dose 2.5 mg bid plus low-dose aspirin may be initiated immediately after successful peripheral revascularization and establishing haemostasis in patients with PAD who are eligible for intensified antithrombotic therapy according to their physician’s discretion. This is good news for patients like Alex, because it means they can receive intensified protection against major adverse vascular events as soon as the treating physician deems it safe to start DPI therapy.

As Professor Rupert Bauersachs explains in the video below: ‘Dual pathway inhibition provides a simple and effective management to the vascular physician, of course, to the patient also, covering the immediate and long-term phase, starting right after the revascularization and continuing long term’.

VOYAGER: The role of rivaroxaban in PAD lower extremity revascularisation patients
VOYAGER PAD results and implications for clinical practice: The vascular physician’s perspective
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External links

References

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Aboyans V et al. Eur Heart J 2018;39:763–816. Return to content
Conte MS, Bradbury AW, Kolh P et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg 2019;69:3S–125S.e140. Return to content
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Fashandi AZ et al. J Vasc Surg 2018;68:1817–1823. Return to content
Hess CN, Norgren L, Ansel GM et al. A structured review of antithrombotic therapy in peripheral artery disease with a focus on revascularization: a TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) initiative. Circulation 2017;135:2534–2555. Return to content
Bonaca MP, Bauersachs RM, Anand SS et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med 2020;382:1994–2004. Return to content
Eikelboom JW, et al. N Engl J Med. 2017;377:1319–1330. Eikelboom JW, et al. N Engl J Med. 2017;377:1319–1330. Return to content
Anand SS et al. Lancet 2018;391:219–229. Return to content

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Updated date 10/10/2022

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Vascular Adviser