The 2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Artery Disease: An interview with SVM members of the writing committee

The recently published ‘2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Artery Disease’ is the first complete revision of these guidelines since 2005. ¹ The 2016 guidelines emphasize awareness and recognition of peripheral artery disease (PAD), review data supporting medical therapies for reduction of cardiovascular events, and highlight the importance of walking programs, revascularization strategies for PAD, and multidisciplinary approaches to the care of patients with critical limb ischemia (CLI). In addition, the guidelines also discuss future areas of research, as well as advocacy priorities to improve the care and outcomes of patients with PAD.

The 2016 guidelines were a multidisciplinary and multisociety effort, and the Society for Vascular Medicine (SVM) played an important role in guideline development and review. Multiple SVM members participated in the writing committee, and the SVM Communications Committee reviewed the draft document prior to publication. These activities demonstrate the impact that medical vascular specialists and vascular interventionalists have nationally on guidelines and medical decision-making. To update SVM members on the guidelines, Ehrin Armstrong, chair of the Communications Committee, interviewed Heather Gornik, Naomi Hamburg, and Scott Kinlay, who were all involved in the guideline writing committee.

How do the new guidelines strengthen recommendations for the awareness and identification of PAD?

Heather Gornik: The 2016 guidelines focus on incorporating an assessment for PAD into routine clinical practice. This starts with taking a vascular history and evaluation of PAD risk factors and symptoms. Too often, physicians do not ask about walking impairment, or fail to link walking impairment with a potential vascular etiology. The 2016 new guidelines emphasize asking about any walking impairment, not just classic calf claudication with exercise. As you know, many patients who have leg symptoms might not have typical claudication, yet still have hemodynamically significant PAD. Investigators such as Mary McDermott and others have really highlighted the importance of recognizing atypical leg symptoms as manifestation of PAD. The guidelines recommend that, in the presence of concomitant risk factors, it is important to perform an ankle–brachial index (ABI) as a targeted evaluation for the etiology of a patient’s leg symptoms and walking impairment. This approach de-emphasizes population screening for PAD, but instead emphasizes focused testing based on the presence of risk factors and walking impairment. The guidelines also recommend performing an ABI with physical findings consistent with PAD, such as pulse deficits or bruits.

The effectiveness of antiplatelet therapy in PAD, and especially aspirin, has been controversial. How do the 2016 guidelines update the recommendations for antiplatelet therapy for patients with asymptomatic or symptomatic PAD?

Naomi Hamburg: The recommendations for aspirin or clopidogrel monotherapy among patients with symptomatic PAD did not change compared to the prior guidelines; antiplatelet therapy for patients with symptomatic PAD remains a Class I indication. The reality is that patients with symptomatic PAD remain undertreated with antiplatelet agents despite these recommendations. For patients with asymptomatic PAD, the guidelines provide different levels of recommendation based on the hemodynamic severity of PAD: for patients with asymptomatic PAD and an ABI of ⩽ 0.90, antiplatelet therapy is a Class IIa recommendation. Among patients with asymptomatic PAD and a borderline ABI, the recommendation for antiplatelet therapy was Class IIb, as there is no definite clinical benefit in that population of patients. Dual antiplatelet therapy has not been shown to have a definitive benefit for the reduction of cardiovascular events in PAD, although dual antiplatelet therapy may be reasonable for reduction of limb-related events after lower extremity revascularization.

With regards to newer antiplatelet agents, the guidelines committee felt that data for vorapaxar did not convincingly demonstrate a benefit over risk (Class IIb). While many are hopeful that there will be additional evidence for this drug and other newer antiplatelet agents for the reduction of limb-related events, specific evidence is lacking. When prescribing antiplatelet agents for PAD, it is also important to remember that the societal guidelines are general recommendations used to advance the standard of care and don’t necessarily address specific patient circumstances, where the risk–benefit ratio may favor more tailored therapy.

Previous guidelines have emphasized the importance of smoking cessation. Do the new guidelines provide any additional recommendations for avoiding smoke exposure or methods for quitting tobacco use?

Naomi Hamburg: Smoking is so pervasive and such a strong risk factor for PAD that it tends to be overlooked. The 2016 guidelines emphasize the importance of developing a smoking cessation plan for all patients with PAD currently using tobacco products. In general, available agents for smoking cessation are safe for use in patients with cardiovascular disease, and are therefore also recommended for patients with PAD. The updated guidelines also recommend avoiding second-hand smoke, as there is compelling evidence that second-hand smoke exposure increases overall cardiovascular risk and likely the risk of developing PAD. While few studies have specifically addressed these exposures among patients with PAD, the overwhelming evidence of cardiovascular risk from second-hand smoke exposure supports this recommendation.

Structured exercise is effective for symptom reduction in claudication, but supervised exercise therapies are difficult to implement. Do the new guidelines recommend alternative walking programs?

Heather Gornik: Supervised exercise therapy remains the gold standard for walking programs for patients with symptomatic PAD, based on the robust data supporting this intervention among patients with claudication. In the past decade, numerous other approaches to structured exercise therapy have been developed, including structured community or home-based exercise programs that incorporate behavioral change techniques. The writing committee carefully considered the emerging data for all of these techniques, and ultimately retained supervised exercise therapy as a Class I recommendation, but a Class IIa recommendation for other structured exercise programs. Unstructured exercise programs (‘go home and walk’) are not effective – there really needs to be a formal structure and supervision by health care providers to make these recommendations work.

The 2016 guidelines include a section on management of acute limb ischemia (ALI), which was not in the 2005 guidelines. What are the highlights of ALI management recommendations?

Scott Kinlay: ALI is a medical and interventional emergency. The guidelines incorporated recommendations for emergent evaluation and determination of limb viability, followed by heparinization and a decision for revascularization. Many options for revascularization exist if the limb remains viable, including catheter-directed thrombolysis or surgical bypass; the decision should be individualized based on patient presentation and local resources. Figure 3 in the Executive Summary provides a helpful algorithm for treatment of ALI that incorporates these guidelines. ¹

The 2016 guidelines also emphasize the importance of a multidisciplinary approach to wound care and medical treatment of patients with CLI. What steps should be taken to coordinate care of patients with CLI?

All: Patients with CLI typically have multiple comorbidities beyond presentation with an ischemic ulcer or rest pain. As a result, multidisciplinary care is paramount to improving the outcomes of these patients. This includes recognition and treatment of cardiovascular risk factors, as cardiovascular events are the major cause of death among patients with CLI. All patients with a non-healing wound should be cared for by an interdisciplinary care team that typically includes podiatrists and/or a wound care specialist in order to maximize healing potential with a goal of complete wound healing after revascularization.

How do the 2016 guidelines handle surgical versus endovascular approaches to revascularization for CLI?

Scott Kinlay: The writing committee recognized the importance of early revascularization for CLI in conjunction with wound healing therapies to prevent limb loss, and medical therapies to prevent cardiovascular ischemic events. The committee did not make overall recommendations on the type of revascularization (endovascular versus open surgical) as the only randomized comparison (the BASIL trial) suggested similar amputation-free survival and included the use of only balloon angioplasty. The ongoing BEST-CLI and BASIL 2 trials will compare these two strategies of revascularization in the contemporary era. The committee recognized that the choice of revascularization depends on weighing the likelihood of technical failure or poor durability with endovascular techniques versus the risks of perioperative complications (largely related to comorbidities) and durability (suitable autologous vein) from open surgery (Table 9 in the Executive Summary of the guidelines). ¹ In order to facilitate decisions in difficult cases, the guidelines recommend an evaluation from an interdisciplinary team prior to major amputation in patients with CLI.

What new recommendations do the guidelines provide on the identification and management of patients with CLI?

Scott Kinlay: The identification of CLI depends on the clinical features of rest pain, non-healing wounds or ulcers, presence of gangrene, and an abnormal ABI. In this setting, an abnormal ABI should lead to anatomical assessment by ultrasound or non-invasive or invasive angiography to determine options for revascularization. Uncertainty in the diagnosis of CLI can occur in patients with non-healing wounds or gangrene and high or normal or borderline ABIs. In this situation, the question is how much of the presentation is due to non-compressible large artery disease (which can be revascularized) and how much is due to microvascular disease, infection, or other causes where revascularization is not indicated. The guidelines concluded that in these uncertain scenarios, it is reasonable to consider other tests such as the toe–brachial index (TBI) with pulse volume recordings (PVRs) to assess arterial perfusion. Transcutaneous oxygen pressure (TcPO₂) and skin perfusion pressure (SPP) were also considered reasonable, as high values with these tests would indicate a higher likelihood of healing with wound care and medical therapy alone. If these tests are abnormal, the guidelines suggest proceeding to ultrasound or angiography to evaluate revascularization options. The validity of TBI, TcPO₂, and SPP is less well-studied than ABI, and there is overlap between patients who heal with wound care alone and those who require revascularization. So, although these extra physiological tests may not necessarily ‘make a diagnosis of CLI’, in uncertain scenarios they may help determine the immediate need for arterial imaging to guide revascularization.

What other evidence gaps and future research directions did the guidelines emphasize?

All: PAD remains understudied relative to other cardiovascular diseases, and many evidence gaps remain. These include translational studies to understand the vascular biology, endovascular and surgical therapies, advancements in PAD diagnostics, randomized studies to identify the utility of ABI testing in asymptomatic patients, development of new classification systems for risk stratification in patients with PAD, and the use of large registries to study quality and population outcomes. By emphasizing these knowledge gaps, the writing committee hopes to direct priorities for future funding and research.

A unique aspect of the 2016 guidelines was the addition of a section on advocacy priorities for patients with PAD. What were the major advocacy priorities that were identified?

All: The 2016 guidelines identified three major areas to improve the care and outcomes of patients with PAD. ¹ First, we recommended that ABI testing be available and reimbursed for patients with not only symptoms, such as claudication, but also those with signs of PAD based on physical examination, such as bruits or pulse deficits. Increased availability of ABI testing would help identify patients with PAD and improve overall cardiovascular risk reduction. Second, the committee felt strongly that supervised exercise programs should be reimbursed, given the overwhelming evidence of benefit. Medicare is currently reviewing a request for a coverage decision on supervised exercise programs, and many SVM members commented during a period of public comment on this topic.^2,3 We are optimistic that coverage may be a reality in the near future. Third, the committee recommended that future device trials include patient-centered outcomes, including wound healing and quality of life metrics. Addition of these patient-centered outcomes would help separate device-related patency from overall benefit to the patient.