Prime time for lower extremity artery disease

May 06, 2020

Lower extremity artery disease (LEAD) is a leading cause of morbidity and mortality worldwide, affecting hundreds of millions of people. On top of that, LEAD also represents a prominent marker of associated coronary artery disease (CAD), as demonstrated by ?70% prevalence of significant CAD in patients with symptomatic LEAD. Accordingly, in the last decades increasing attention has been devoted to the management of LEAD, including antithrombotic strategies in asymptomatic patients, symptomatic patients and following surgical or endovascular revascularization.

The large randomised COMPASS (Cardiovascular Outcomes for People Using Anti-coagulation Strategies) trial recently demonstrated that an intensified antithrombotic regimen comprising rivaroxaban 2.5 mg twice daily on top of aspirin is associated with an impressive 46% reduction in major adverse limb events (acute and chronic limb ischaemia including major amputation) as compared to aspirin alone; importantly, this therapeutic strategy can be cost-effective in patients with peripheral artery disease.

However, while attention has been given to the definition of the best long-term antithrombotic strategy for the secondary prevention of patients with LEAD, the same is not true regarding the treatment of patients undergoing peripheral vascular interventions (PVIs), whose medical management has been largely extrapolated from the coronary field. This aspect is of particular relevance considering the high number of patients in whom lower limb revascularization is currently indicated, such as both those at risk of limb amputation or with lifestyle-limiting claudication. Over recent years, the number of PVIs has soared worldwide, driven by a consistent improvement of endovascular techniques and devices. While this growth has been accompanied by many clinical trials aimed at assessing the safety and efficacy of the various revascularisation strategies, very little evidence was collected regarding the best antithrombotic treatment in patients undergoing PVI.

With these considerations in mind, we aimed at outlining the "state-of-the-art" of antithrombotic therapy for peripheral revascularisation, hopefully contributing to a better management of LEAD patients in clinical practice, which is actually the mission of the Working Group on Aorta and Peripheral Vascular Diseases of the European Society of Cardiology, which I recently had to honour to chair.

Our review, published in the last Special Issue of Current Vascular Pharmacology, provides an overview of the indications and techniques of lower extremity revascularisation, and an in-depth analysis of the available evidence regarding type and duration of antiplatelet and anticoagulant treatment following endovascular and surgical revascularisation. A specific focus was dedicated to endovascular revascularisation, whose growth in number has not been accompanied by a parallel growth in high-quality scientific evidence regarding antithrombotic therapy. In the lack of dedicated randomised trials, we pragmatically analysed and compared the antithrombotic strategies recommended in the randomised trials dedicated to endovascular devices and techniques.

Of notice, during the ACC congress in March 2020, shortly after the publication of our review, the results of the VOYAGER PAD study ("Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD") were presented. This trial demonstrated that, in patients undergoing lower limb revascularization (65% endovascular), the combination of a low-dose anticoagulation with rivaroxaban (2.5 mg bid) on top of aspirin is associated with significantly lower limb-related and major vascular events than aspirin ± clopidogrel (17.3% vs 19.9% at 3 years, respectively), with a limited increase in major bleedings (5.9% vs 4.1%). However, despite rivaroxaban 2.5 mg bid + aspirin has the potential to become the reference treatment strategy in patients undergoing lower limb revascularization, in the absence of favourable cost-effective analysis and waiting for the approval of regulatory agencies, a rapid worldwide implementation of the results of the VOYAGER PAD study in clinical practice is unlikely. Therefore, our review provides a useful guidance on antithrombotic treatment for both endovascular and surgical revascularisation procedures in current clinical practice.
Keywords: Lower extremity artery disease, peripheral vascular interventions, vascular surgery, antiplatelets, anticoagulants, antithrombotic treatment.

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Bentham Science Publishers

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