Infrainguinal Disease: Endovascular Therapy

Introduction

The use of endovascular therapies for the treatment of infrainguinal vascular disease has become a key component of a multimodal approach to manage peripheral arterial disease. The decision to employ an endovascular-first interventional strategy relies on several factors, including clinical presentation, lesion anatomy, patient comorbidities and presence of autologous conduit. Most importantly, endovascular therapy should serve as a complement to other methods of treatment, including medical management and open surgical approaches. As such, it is paramount that the vascular practitioner recognizes the advantages and limitations of the various endovascular strategies, ranging from diagnostic angiography to intervention with balloon angioplasty, stenting and even atherectomy. An “on-hand” knowledge of multiple endovascular techniques is especially important, as diagnostic angiography may serve to delineate disease that is amenable to intervention in the same setting. Indeed, the likelihood of success is predicated on the right tool at the right time, meaning both the right technique and the right indication. This chapter will serve as a review of the endovascular interventions, based on indication, currently available for infrainguinal disease.

Indications

Medical Management

Endovascular therapy often represents an attractive “minimally invasive” option, especially for patients with intermittent claudication with isolated, short segment lesions. However, it is best utilized as a component of an overarching strategy (rather than standalone therapy) to help manage chronic, progressive diagnosis. A key component in the management of these patients involves adherence to non-interventional strategies including smoking cessation, tight control of blood glucose levels in diabetic patients, use of appropriate antiplatelet and statin therapy, and enrollment in a supervised walking program. Adherence to medical optimization and enrollment in a supervised walking program is a key component at every stage of managing these patients, and certainly may be the most appropriate initial management before one even considers utilizing invasive measures. In the context of this chapter, it is important to consider medical optimization as an important adjunct to reduce surgical risk and improve anticipated outcomes following endovascular procedures.

Smoking Impact

Smoking cessation is a cornerstone in the management of patients with peripheral artery disease (PAD) and is recommended by American Heart Association (AHA), Society for Vascular Surgery (SVS) and Global Vascular Guidelines. Patients who present with IC and are actively smoking rarely progress to chronic limb-threatening ischemia (CLTI) and have improved cardiovascular survival if they can maintain smoking abstinence. Active smokers who undergo an open bypass have a threefold increased risk of graft failure. Those that quit smoking after their bypass experience a 50% risk reduction in all-cause mortality over the ensuing 5 years. However, a similar increase in risk of adverse limb events, including reintervention, conversion to surgical bypass and limb loss, following endovascular intervention in active smokers has not been appreciated.

Statin Impact

Statin therapy, and in particular high-intensity statin therapy, has been shown to reduce rates of major adverse limb events and mortality in patients with peripheral artery disease. In the international First-Line Treatments in Patients with Critical Limb Ischemia (CRITISCH) registry, statin therapy demonstrated a significant survival benefit in patients with CLI, though amputation rates are similar to patients not on statin therapy. Patients undergoing endovascular revascularization have better outcomes when combined with statin therapy use. In a review of nearly 650 patients undergoing endovascular intervention, statin therapy was associated with an increased rate of primary patency, secondary patency, limb salvage and overall survival.

ACE Inhibitor Impact

Overwhelming evidence has supported the use of angiotensin converting enzyme (ACE) inhibitor therapy in patients with PAD to reduce cardiovascular mortality. Recent research in patients undergoing a heterogenous mix of endovascular therapies for lower extremity disease demonstrated an improved overall survival and amputation-free survival among patients on ACE inhibitor therapy. ^,

Antiplatelet Therapy Impact

Antiplatelet therapy has become a mainstay among patients with PAD, largely due to the high prevalence of comorbid coronary or cerebrovascular disease. However, evidence of benefit for using antiplatelet therapy for primary prevention of cardiovascular outcomes (including peripheral events) in asymptomatic patients with PAD are lacking. ^, In contradistinction, multiple studies have demonstrated the significant cardiovascular risk reduction among symptomatic patients taking single antiplatelet therapy (either aspirin 75–325 mg or clopidogrel 75 mg monotherapy). Intermittent claudication is the predominant symptom for most patients within these trial populations. Despite these positive results, a meta-analysis by Berger et al., including asymptomatic and symptomatic patients, failed to demonstrate a significant difference in major adverse cardiovascular outcomes. Considering the potential positive impact of antiplatelet therapy for cardiovascular risk reduction in patients with atherosclerotic PAD, and the relatively low rates of bleeding complications, many practitioners have adopted the utilization of antiplatelet therapy in their medical management strategy for patients with PAD. Indeed, numerous societal guidelines, including the AHA 2016 Guideline Statement and SVS Practice Guideline Statement, provide Class 1A recommendations for the use of antiplatelet therapy for patients with symptomatic PAD. ^, The use of newer antiplatelet therapies, such as ticagrelor, has become more prevalent with the improved results in patients taking this medication following PCI for MI though it does not demonstrate similar superior outcomes compared with Plavix monotherapy in patients with PAD. The use of antiplatelet therapy after percutaneous intervention is discussed in more detail later in this chapter.

Anticoagulation Therapy Impact

With the recent publication of the COMPASS trial, there has been a renewed interest in the use of long-term anticoagulation for patients with symptomatic PAD. Within this trial, over 28,000 patients with cardiovascular disease in at least two beds or with at least two risk factors were randomized to low dose rivaroxaban, either alone (5 mg twice daily) or with aspirin (2.5 mg plus 100 mg aspirin daily) compared with aspirin alone (100 mg daily). With a median follow-up of 23 months, there were lower rates of a composite endpoint of cardiovascular outcomes (5% compared with 7%) and, importantly, fewer major adverse limb events including amputation (1% vs. 2%) among the patients with combination therapy of low dose rivaroxaban plus aspirin compared to aspirin alone. Nearly 7500 patients within this study had PAD and nearly 25% had a previous revascularization procedure. Subgroup analysis of this population further supported an improved outcome on patients with low dose rivaroxaban plus aspirin. These results helped to inform the design of the VOYAGER trial, which focused specifically on the population of PAD patients undergoing revascularization. The results of this are discussed later in the chapter.

Intermittent Claudication

To date, overwhelming evidence supports the role of medical management as the first-line therapy for patients with intermittent claudication (IC).2 With appropriate medical management, few patients (1%–3%) with IC will progress to require amputation over the ensuing 5-year period. Surgical therapy, either open or endovascular, for patients with PAD with symptoms limited to IC is a reasonable strategy for those who fail medical management, including supervised waking therapy. ^, If CT angiography is inadequate, the use of invasive angiography for patients who continue to have lifestyle-limiting claudication after best medical management can function as both an anatomic assessment and therapeutic intervention strategy. “Failure” of medical management represents an individualized discussion between the patient and the vascular surgeon. In the real world, multiple reasons can contribute to failure of medical management, including patients who cannot modify their lifestyle, those that do not have access to supervised walking programs, and those who have personal reasons for a more aggressive approach to intervention (e.g., walking is a key part of their employment). It is incumbent on the vascular surgeon to recognize the available interventions, their likelihood of success and the associated risks to appropriately guide patients through the management of this disease. Importantly, current societal guidelines recommend against the treatment of IC solely for the purpose of preventing progression to CLTI.

Endovascular therapies, including balloon angioplasty, stenting, or atherectomy, for IC have limited level 1 data regarding long-term durability, especially compared to supervised walking therapy. Much of the data for newer therapies are from industry-sponsored trials, which may have limited follow-up data, as they are often designed (understandably) for regulatory clearance. Further complicating the picture is the fact that many of these trials include a heterogeneous group of patients, including IC and CLI. Patients with IC actually comprise a large portion of the total included patients. Given the overall benign course of most patients with intermittent claudication, it is highly prudent for only inventions with durable benefits to be considered. The types of outcomes reported may make it difficult to interpret the actual value of endovascular intervention. Specifically, the use of “target vessel revascularization” (TVR) as an outcome measure may prioritize angiographic or anatomic evidence of success, rather than patient-reported outcomes or qualitative measures such as walking distance or amputation-free survival. For instance, a meta-analysis by Wilson examined six trials comparing PTA and stenting with medical therapy and found a significant increase in ABI following endovascular therapy versus medical management. However, at 6 months, patients in the medical management group actually reported longer walking distances compared to those that had undergone endovascular therapy, a result maintained at 1 to 2 years in the majority of the trials. TVR undoubtedly imparts a cost to the patient and healthcare system and is important to consider; however, results reported herein will be centered around amputations, thrombosis or bleeding events, and patient-reported quality of life (QoL) scores whenever possible.

Femoropopliteal Segment

The femoropopliteal segment (FPS) is the most common affected infrainguinal area for patients with intermittent claudication. Lesions in this region that appear to compromise 50%–75% of the diameter of the lumen likely cause a hemodynamically significant reduction in flow. Lesions isolated to the common femoral artery are nearly universally better served with open femoral endarterectomy and patch angioplasty, allowing for preservation of the profunda. ^, In patients with hostile groins, there are reports of endovascular approaches involving both angioplasty and stenting, with care taken not to cover the orifice of the profunda artery. ^, To reduce the rates of dissection and vessel occlusion when treating CFA lesions, some have even reported the use of kissing stents, though these reports lack long-term follow-up and are limited in number.

Endovascular therapy has become first-line therapy for managing stenosis or occlusions in the superficial femoral artery extending into the popliteal segment, especially those with short lesions measuring less than 4 cm. ^, ^, The sheer number of available treatment options, including plain balloon angioplasty (PBA), atherectomy, bare metal stent (BMS) placement, stent graft placement and, more recently, drug-incorporating therapies (drug-coated balloon [DCB] angioplasty and drug-eluting stent [DES] placement), offer the practitioner a wide gamut of tools to utilize an endovascular approach disease in these segments. The infrainguinal vessels are highly dynamic, with a combination of axial and radial forces exerted on the vessel during locomotion as well as the challenge pinching of the artery that can occur predominantly at the adductor hiatus. Compression on these segments can increase three- to fivefold as the patient ages through an increase in the presence of calcific plaques as well as a change from atheroprotective wall shear stress to atherosclerosis-inducing oscillatory shear stress. Indeed, an improved recognition of these forces has been at the heart of device development, and has led to designs that resist both the mechanical as well as cellular response to intervention.

Balloon Angioplasty

During the early development of endovascular technology in the 1980s and 1990s, PBA was the primary tool for management of lesions in the FPS. PBA functions to disrupt atherosclerotic plaques by increasing the lumen diameter, with balloon sizes chosen based on a combination of characteristics of the vessel both at the disease location and at a normal location, presumably distal to the diseased segment. Dissections are a common effect of this mechanical disruption, and are a key factor limiting the effectiveness and durability of PBA as a stand-alone therapy. Severe dissection can occur following PBA, and “bailout” stenting is frequently required, most typically in cases with residual stenosis or flow-limiting dissections. Further, the trauma induced by balloon inflation can lead to continued inflammation within the artery and activation of leukocyte adherence, smooth muscle cell migration into the intima, and macrophage recruitment into the ECM. In combination, this response to balloon angioplasty results in “negative remodeling” and promotes restenosis in the treated segment.

Much of the recent data regarding long-term patency of primary balloon angioplasty in combination with maximal medical management are derived from comparisons with drug-coated balloon angioplasty. While the effectiveness of the latter strategy is discussed more fully elsewhere in this chapter, a review of these results helps to demonstrate the limited durability of primary balloon angioplasty in the FPS. In the European BIOLUX P-I trial, the uncoated balloon angioplasty arm had a 34.6% restenosis rate with target vessel revascularization required in 41.7% of treated vessels at 1 year. Similarly, in a clinical trial comparing paclitaxel-coated balloon versus PBA, patients treated with PBA had a high rate of target vessel revascularization (33.3% at 6 months). Interestingly, Rutherford class was only improved in 36% of patients after PBA at 6 months, though that rate stayed stable through 18–24-month follow-up. In the IN.PACT SFA trial, patients with Rutherford stage 2–4 symptoms (with the majority Rutherford 2 and 3) were randomized to angioplasty with either DCB or PBA. Primary patency for the PBA group was only 50.1% at 24 months and 29.2% required target vessel revascularization, though no patients had a major limb amputation in a treated limb during the study period. These results are concordant with a large Cochrane Review that demonstrated no difference in limb amputation rates at 5 years for patients undergoing uncoated PBA compared with angioplasty with DCB, despite significant differences in TVR between DCB and PBA (favoring DCB). PBA as a stand-alone therapy may have its greatest usefulness in patients with short lesions (<4 cm) who are willing to participate in aggressive post-interventional medical management and lifestyle changes, as well as routine follow-up with a vascular surgeon.

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