Author’s Accepted Manuscript

2016 American College of Cardiology/American

Heart Association Guideline on the Management of
Patients with Lower Extremity Peripheral Artery
Disease: Perioperative Implications

Elizabeth A. Valentine, E. Andrew Ochroch

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PII: S1053-0770(17)30472-X
DOI: http://dx.doi.org/10.1053/j.jvca.2017.04.048
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To appear in: Journal of Cardiothoracic and Vascular Anesthesia
Cite this article as: Elizabeth A. Valentine and E. Andrew Ochroch, 2016
American College of Cardiology/American Heart Association Guideline on the
Management of Patients with Lower Extremity Peripheral Artery Disease:
Perioperative Implications, Journal of Cardiothoracic and Vascular Anesthesia,
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2016 American College of Cardiology/American Heart Association Guideline on the

Management of Patients with Lower Extremity Peripheral Artery Disease: Perioperative

Implications

Elizabeth A. Valentine, MDa and E. Andrew Ochroch, MD, MSCEa

a
Department of Anesthesiology and Critical Care
Hospital of the University of Pennsylvania
3400 Spruce Street
Philadelphia, PA 19104

Corresponding Author:
Elizabeth Valentine, MD

Department of Anesthesiology and Critical Care

Hospital of the University of Pennsylvania
3400 Spruce Street
6 Dulles Building
Philadelphia, PA 19104

elizabeth.valentine@uphs.upenn.edu
(215) 285-2466

Funding: none
Conflicts of interest: none
Acknowledgments: none

Invited Review Article by Dr. John G.T. Augoustides

Lower extremity peripheral artery disease (PAD) is a common manifestation of atherosclerotic

cardiovascular disease, estimated to affect approximately 8.5 million Americans above the age

of 40 and more than 200 million people worldwide.1 PAD portends a poor prognosis both

because of its detrimental effect on physical functioning as well as its association with

atherosclerotic cardiovascular disease in other regions; namely, the coronary, cerebrovascular,

and renovascular systems.2-4 In the Reduction of Atherothrombosis for Continued Health

(REACH) registry, a large international registry of more than 65,000 patients spanning more

than forty countries across six major regions (Latin America, North America, Europe, Asia, the

Middle East, and Australia), approximately one in six patients with atherosclerotic

cardiovascular disease had evidence of symptomatic polyvascular disease, including the

majority of patients with PAD.3 A 2008 meta-analysis of nearly 50,000 patients demonstrated

that men who carry a diagnosis of PAD have a 3-fold risk of all-cause death compared to men

without PAD, with a similar risk in women.5

Given the widespread prevalence of PAD, associated morbidity and mortality, and detrimental

effect on quality of life, multiple groups have issued guidelines to outline optimal management of

patients with PAD.6-13 In 2016, the American College of Cardiology/American Heart Association

(ACC/AHA) Task Force on Clinical Practice Guidelines released an update on the management

of patients with lower extremity PAD.8 In addition to an evidence-based update to all

recommendations using the latest evidence classification system,14 this guideline seeks to

address three clinical questions: 1.) Is antiplatelet therapy beneficial for prevention of

cardiovascular events in patients with both symptomatic and asymptomatic lower extremity

PAD? 2.) What is the effect of revascularization, compared with optimal medical therapy and

exercise training, on functional outcomes and quality of life measures among patients with
intermittent claudication (IC)? and 3.) Is one revascularization strategy (endovascular versus

surgical) associated with improved outcomes in patients with critical limb ischemia (CLI)? The

purpose of this review is to highlight the changes in recommendations in the management of

PAD, with a focus on medical optimization and procedural interventions, as well as to discuss

the perioperative relevance to the cardiovascular anesthesiologist.

Clinical Assessment of Peripheral Artery Disease

The current literature suggests that PAD is both underdiagnosed and undertreated, despite a

preponderance of evidence to suggest that aggressive management of PAD decreases major

morbidity and mortality associated with atherosclerotic cardiovascular disease. Underdiagnosis

may be due in large part to the fact that only approximately 10% of people with PAD present

with classic symptomatology, and up to two-thirds of patients are asymptomatic.1 This guideline

encourages more aggressive screening for PAD in the general population compared to previous

iterations (Table 1). Patients identified to be at increased risk of PAD include patients age ≥ 65

(previously 70), age 50-64 years with risk factors for atherosclerotic cardiovascular disease or a

family history of PAD (not solely those with diabetes or a history of smoking), age <50 with

diabetes mellitus and one additional risk factor for atherosclerotic cardiovascular disease, and

individuals with known atherosclerotic cardiovascular disease in another vascular regions. The

updated guideline also recognizes that the majority of patients with confirmed PAD do not

present with typical symptoms of IC and advocates more aggressively for consideration of

atypical exertional lower extremity symptoms as an IC equivalent (Table 2). Resting ankle-

brachial index (ABI) is a simple, noninvasive test that compares the blood pressure in the upper

and lower extremities (abnormal ABI ≤0.90, borderline ABI 0.91–0.99, normal ABI 1.00–1.40,

and noncompressible ABI >1.40).15 ABI (or toe-brachial index, for patients with suspected PAD

and non-compressible arteries) remains the recommended initial diagnostic test of choice for
suspected PAD. Exercise treadmill ABI is recommended for patients with exertional symptoms

and normal or borderline resting ABIs in order to evaluate for PAD.

An overall increase in the strength of the recommendations supporting more aggressive

screening, coupled with an aging population, will likely lead to an increase in the prevalence of

PAD diagnosed in the general population. Whether that will, in turn, lead to an increase in

interventional procedures remains to be seen. It is worth noting that while the guideline

advocates for more aggressive screening for PAD, it also cautions more judicious use of testing

and resources. This guideline offers a Class III (no benefit) recommendation against routine

measurement of ABI in patients not at risk of PAD or without a history or physical exam

suggestive of PAD, as well as a Class III (harm) recommendation against invasive

(angiography) or non-invasive (e.g., computed tomography angiography or magnetic resonance

angiography) imaging for routine anatomic assessment, unless revascularization is being

considered. This is a change from previous recommendations, which favored more routine

imaging for diagnosis and management.

Medical Optimization of Peripheral Artery Disease

The importance of behavioral and lifestyle modifications continues to be emphasized as a

cornerstone of the treatment of PAD (Table 3). Patients should be advised to quit smoking with

every visit, and providers should assist in developing a smoking cessation plan, which should

include pharmacotherapy, referral to a smoking cessation program, or both (Class of

Recommendation [COR] I, Level of Evidence [LOE] A). An increased recognition of the

detrimental effect of second- and third-hand smoke exposure in the development of PAD16, 17

has led to a new recommendation for patients with PAD to avoid environmental smoke

exposure (COR IIa, LOE B-NR). Data have long supported structured exercise programs for the
treatment of PAD. Structured exercise programs typically involve a minimum of 30 minutes per

session, performed at least 3 times per week, for a minimum of 12 weeks.8 Multiple randomized

controlled trials have suggested that supervised exercise programs result in superior functional

outcomes when compared to optimal medical care alone.18-20 Conversely, recommendations for

unstructured home- or community-based walking (e.g., simply telling a patient to “walk more”)

have not been shown to be efficacious.21 Recent evidence suggests that structured, though not

necessarily supervised, home- or community-based exercise programs can have a significant

improvement on functional parameters and help prevent mobility loss.22-25 In light of these data,

a new recommendation has been issued in support of structured home- or community-based

exercise programs (COR IIa, LOE A). This is an important modification to previous

recommendations, as significant barriers, including functional limitations, physical proximity, and

financial issues, may prevent many patients with PAD from participating in supervised

programs.

Superior preoperative fitness levels have been associated with improved survival for both major

vascular as well as major intra-abdominal surgery,26 and increased participation in structured

exercise programs as “prehabilitation” may improve overall fitness for surgery. Studies of

preoperative exercise therapy have demonstrated improved markers of physical fitness in both

vascular and general surgery patients, though whether that translates to fewer complications is

less clear.27, 28 At minimum, greater participation in preoperative exercise programs may assist

in risk stratifying patients prior to surgery per most recent guidelines.29 It has been estimated

that approximately $81-180 million dollars are spent annually in the Medicare population on

unnecessary stress tests.30 From a public health perspective, structured exercise programs may

not only improve quality of life outcomes in PAD, but also may provide critical information to the

perioperative team to eliminate unnecessary testing and procedures. Anesthesiologists, as

experts in perioperative optimization prior to surgery, can and should advocate for patient

participation in structured exercise programs in this patient population prior to surgical

intervention whenever possible.

The current literature suggests that the medical management of PAD tends to be far less

aggressive than atherosclerotic cardiovascular disease diagnosed in other vascular beds. The

PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program

found that hypertension and hyperlipidemia were treated less frequently, and antiplatelet

medications prescribed less often, in patients with PAD as compared to those with coronary or

cerebrovascular disease.31 These results are consistent with those from the REACH registry,

which suggests that only 70% of PAD patients receive appropriate lipid-lowering therapy, 50%

are appropriately treated for hypertension, and only 82% receive antiplatelet therapy for

secondary prevention of atherosclerotic cardiovascular disease.3 When treated, PAD patients

often fail to meet goals set by current guidelines.32, 33 In light of this evidence, this guideline

continues to advocate for aggressive treatment of comorbid conditions including hypertension,

hyperlipidemia, and diabetes mellitus.

The role of antiplatelet agents – and specifically, the role of dual antiplatelet (DAPT) therapy and

newer antiplatelet agents – is addressed in this guideline (Table 4). This guideline continues to

strongly endorse antiplatelet therapy to reduce the risk of myocardial infarction (MI), stroke, or

vascular death in patients with symptomatic PAD. This recommendation is based in large part

on the Antithrombotic Trialists’ Collaboration meta-analysis of 287 randomized trials (including

more than 200,000 patients) of antiplatelet regimens in patients with PAD.34 This study found

that treatment with antiplatelet therapy reduced the combined outcome of any serious vascular
event by nearly one quarter, non-fatal MI by one third, non-fatal stroke by one quarter, and

vascular mortality by one sixth. A subgroup analysis of the Clopidogrel versus Aspirin in

Patients at Risk of Ischemic Events (CAPRIE) trial found that clopidogrel was more effective

than aspirin in reducing the combined risk of MI, ischemic stroke, or vascular death in subjects

with PAD.35 On the basis of this evidence, the guideline recommends either aspirin alone (75-

325mg daily) or clopidogrel alone (75 mg daily) to reduce the risk of MI, stroke, or vascular

death in patients with symptomatic PAD (COR I, LOE A). The guideline further suggests that

antiplatelet therapy is reasonable in patients with asymptomatic PAD (COR IIa, LOE C-EO), and

that the benefit is uncertain (COR IIb, LOE B-R) for patients with borderline PAD. Both of these

recommendations are based on limited data in these populations.

This updated guideline modifies previous recommendations regarding DAPT in patients with

symptomatic PAD. The previous iteration was the first to address the role of DAPT for PAD and

recommended that a combination of aspirin and clopidogrel may be considered to reduce risk of

cardiovascular events in patients with symptomatic PAD, prior to revascularization

(endovascular or surgical), or prior to amputation, in patients who are high perceived

cardiovascular risk and who are not at increased risk of bleeding.7 This recommendation was

based largely on the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization,

Management, and Avoidance (CHARISMA) trial.36-38 The 2016 update modifies this

recommendation based largely on the same evidence, stating instead that efficacy of DAPT

therapy to reduce the risk of cardiovascular ischemic events in patients with symptomatic PAD

is not well established (COR IIb, LOE B-R). Additional clinical trials are needed to further define

the role for DAPT in IC, particularly with newer P2Y12 antagonists available. DAPT may be

considered on an individual basis for those patients thought to be at highest risk of

cardiovascular ischemic risk with low risk of bleeding. Several recent small, randomized
controlled trials demonstrate a decreased need for reintervention following revascularization

procedures when DAPT is employed postoperatively,39-41 and the use of DAPT has been

associated with prolonged survival in CLI patients who undergo intervention.42 This population

may derive particular benefit from DAPT.

A new addition to the 2016 guideline is a recommendation regarding the use of vorapaxar

(Zontivity®) in PAD. Vorapaxar is a novel platelet antagonist that offers a unique mechanism of

platelet inhibition. In contrast to other antiplatelet agents, which exert their antiplatelet effects via

adenosine diphosphate, collagen, and thromboxane pathways, vorapaxar interferes with platelet

aggregation by selectively inhibiting thrombin from binding to protease-activated receptor

(PAR)-1.43 The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic

Ischemic Events – Thrombolysis in Myocardial Infarction 50 (TRA 2oP-TIMI 50) trial found that

the addition of vorapaxar to standard antiplatelet therapy reduced the risk of adverse

cardiovascular events, but increased the risk of moderate to severe bleeding, in patients with

stable atherosclerotic cardiovascular disease.44-46 In the subgroup of patients with PAD,

vorapaxar did not decrease the risk of cardiovascular death, MI, or stroke, but did significantly

reduce the incidence of acute limb ischemia and need for peripheral revascularization.46, 47 This

benefit came at the expense of increased bleeding. The Thrombin Receptor Antagonist for

Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar to

standard therapy in patients with non-ST-segment elevation acute coronary syndrome.48 The

addition of vorapaxar did not decrease the composite endpoint of cardiovascular death, MI, or

stroke in the subset of patients with PAD. In contrast to the TRA 2oP-TIMI 50 trial, there was not

a statistically significant decrease in rates of peripheral revascularization or amputation. Given

these results, the ACC/AHA task force concluded that the benefit of vorapaxar in addition to

standard therapy is uncertain (COR IIb, LOE B-R). The clinical benefit of a reduction in
peripheral ischemic events must be weighed against the risk of serious bleeding on an

individual basis. Further study is warranted, particularly to identify patients at highest risk of

ischemic complications and low risk of bleeding, who are likely to benefit most.

Whether to continue or discontinue antiplatelet agents in the perioperative period is a complex

decision and a source of continued debate in the literature. Recommendations on the

perioperative management of antiplatelet agents are not made in this guideline, but are

addressed elsewhere.29 While a review of antiplatelet agents in the perioperative period is

outside the scope of this review, factors that must be taken into consideration include the

proposed procedure, the individual risk of bleeding versus risk of adverse cardiovascular event,

and the indication for therapy.39, 49-53 Any decision to start or stop antiplatelet agents in the

perioperative period should be made by a multidisciplinary team including vascular medicine,

surgery, and anesthesiology specialists.

Perioperative use of antiplatelet therapy can have significant implications for the

anesthesiologist, particularly for patients undergoing open surgical procedures. Regional

anesthesia has long been advocated for peripheral vascular surgery for its improved

hemodynamic stability, decreased catecholamine surges, and resulting sympathectomy which

may improve peripheral blood flow. Despite the purported benefits of regional anesthesia,

reviews of the American College of Surgeons National Surgical Quality Improvement Program

(NSQIP) database have not consistently demonstrated an association between anesthetic

technique and perioperative cardiovascular morbidity.54, 55 Multiple studies, however, have

suggested an association between general anesthesia and an increased incidence of graft

failure requiring regrafting, revision, or embolectomy.56, 57 General anesthesia may pose other
additional risks, such as airway or pulmonary complications. The use of antiplatelet agents, and

specifically P2Y12 antagonists, may limit options for regional anesthesia per current

guidelines.58, 59 It is worth noting that the American Society of Regional Anesthesia and Pain

Medicine (ASRA) evidence-based guidelines on regional anesthesia in patients receiving

antithrombotic therapy caution against both neuraxial anesthesia and peripheral nerve blockade

when P2Y12 antagonists are in active use.58 Patients undergoing open revascularization for PAD

are increasingly maintained on P2Y12 antagonists in the perioperative period, however, as the

literature suggests no significant increase in bleeding or transfusion in this population.60, 61 With

regard to vorapaxar, it is also important to recognize that the effective half-life is quite long at 3-

4 days.62 The minimum hold period for vorapaxar prior to regional anesthesia has not yet been

established.

Medical Versus Surgical Management of Intermittent Claudication

The second clinical question that this update attempts to address is when, and how, intervention

is warranted for IC.6 The majority of patients with PAD are asymptomatic or have a relatively

benign, indolent progression of their disease. First line therapy for the majority of patients is

typically intensive lifestyle modification and medical management as discussed above. Some

patients, however, have aggressive disease progression despite compliance with prescribed

care. Determining functional impairment and impact on quality of life in these patients is not

straightforward. Minor symptoms may be perceived as intolerable for an active patient, whereas

even severe symptoms may not be as burdensome to a sedentary individual. Since the goal of

treatment is improvement in quality of life, the question of when to proceed with

revascularization is a personal decision that must be tailored to the individual patient. This

guideline continues to emphasize that patient preferences and goals must be taken into

consideration when deciding to attempt revascularization. The guideline stresses that there
should be a reasonable likelihood of providing durable relief of symptoms. The final conclusion

is that revascularization is reasonable for patients with lifestyle-limiting claudication symptoms

with an inadequate response to guideline-directed management and therapy (COR IIa, LOE A).

Current options for revascularization include open surgical procedures, endovascular

interventions, or a combined hybrid approach. In ensuing decade since recommendations were

last made, improvements in technology, equipment, and techniques have led surgeons and

proceduralists to widely adopt an “endovascular first” approach to even the most complex of

anatomic lesions. Thus, while previous iterations advocated for endovascular interventions only

for short, anatomically simple lesions, the current iteration advocates for an endovascular

approach even for aggressive disease, unless technical factors favor surgical intervention.

Modern therapeutic options include angioplasty (including both drug-coated and cutting

balloons), stents (covered and drug-eluting), and atherectomy. The existing literature can be

difficult to compare, given the wide range of therapeutic options employed in modern

endovascular therapy. Accordingly, a comparison of different endovascular techniques was

deemed beyond the scope of this guideline. This is a change from the previous iteration, which

evaluated specific endovascular interventions in greater detail.6 Recently, both the Society for

Vascular Surgery (SVS) and the Inter-Society Consensus for the Management of Peripheral

Arterial Disease (TASC II) released updated practice guidelines for the management of IC that

evaluate different endovascular approaches in greater detail.11, 13

In this guideline, recommendations regarding endovascular intervention are offered by anatomic

location: aortoiliac, femoropopliteal, or infrapopliteal. Endovascular interventions are proposed

as an effective revascularization option for patients with lifestyle-limiting claudication and

aortoiliac disease (COR I, LOE A). This endorsement is based on multiple systematic reviews

and randomized controlled trials that demonstrate endovascular repair to be superior to medical
management alone, and comparable (and in some cases superior) to medical management and

structured exercise programs.20, 63-65 This recommendation is consistent with other societal

recommendations that advocate for an endovascular approach to inflow lesions, including for

complex anatomic disease.10, 11, 13 Endovascular revascularization is deemed a reasonable

option for symptomatic femoropopliteal disease (COR IIa, LOE B-R), based on several

systematic reviews.64, 66, 67 This recommendation is also generally consistent with other societal

recommendations, which promote consideration of endovascular interventions for focal disease

but advocate for consideration of open repair for very complex lesions.11, 13

Isolated infrapopliteal disease rarely causes significant claudication, and infrapopliteal

endovascular interventions have questionable long-term durability with significant ischemic

risks. Historically, treatment of infrapopliteal disease has been reserved for CLI. Limited data

exists to guide decision making for endovascular interventions for IC, particularly in regard to

novel technologies available. Several newer randomized controlled trials suggest that there

may be a role for endovascular interventions with drug-eluting stents in infrapopliteal lesions

with IC.68, 69 Further studies are warranted to establish what role, if any, revascularization plays

for this patient population. Due to the current paucity of literature regarding endovascular

interventions for infrapopliteal lesions, the guideline concludes that the utility of endovascular

interventions for isolated infrapopliteal lesions is unknown (COR IIb, LOE C-LD). This

recommendation aligns with the most recent TASC II update, which concluded that no firm

recommendation can be made based on current evidence.11 SVS recommendations expressly

caution against endovascular interventions for isolated infrapopliteal disease, due to unproven

benefit and possible harm.13

Alternatively, surgical intervention is recommended as a reasonable revascularization strategy

for patients with IC with inadequate response to guideline-directed management and therapy,

assuming both acceptable perioperative risk and that technical factors favor an open over

endovascular approach (COR IIa, LOE B-NR). This is consistent with other societal guidelines

that recommend medical, anatomic, and technical considerations be taken into consideration

when deciding between endovascular and surgical approaches.10, 13 Randomized controlled

trials that directly compare surgical and endovascular treatments are rare, and conclusions

drawn from observational studies are likely prone to bias. For these reasons, it can be difficult to

draw conclusions on superiority of approach (open versus endovascular) or technique for

revascularization. It is imperative to take into consideration proceduralist skill and experience,

access to appropriate technology and imaging capability, and availability of a multidisciplinary

care team necessary to appropriately manage these patients perioperatively. Increasingly, a

hybrid approach may be used to approach more complex lesions.

Revascularization Strategy for Critical Limb Ischemia

A minority of patients with PAD will develop CLI, which typically results from aggressive,

multisegmental disease. Patients with CLI are also at increased risk for more aggressive

atherosclerotic disease in other distributions, including the coronary and cerebral vasculature.

With one year, more than 20% of patients will progress to amputation, and the mortality rate is

also greater than 20%.70 Why PAD progresses more rapidly and relentlessly in some patients is

not completely understood. Patients with diabetes mellitus are known to be at increased risk for

both PAD and CLI. Diabetic patients with poor glucose control are at an increased risk of

amputation and poorer surgical outcomes following procedural intervention.71, 72 Smoking is also

a notable risk factor for CLI.10 In contrast to IC, where the decision for intervention is largely

based on individual preference, the increased risk of nonhealing wounds and pending
amputation generally mandates revascularization for CLI. Nonrevascularization-based

regimens have not generally proven successful in this population.73 Based on the more

aggressive natural history of CLI, the guideline recommends revascularization for CLI to

minimize likelihood of tissue or limb loss (COR I, LOE B-NR). The goal of revascularization,

regardless of technique employed, is to restore in-line blood flow to decrease ischemic pain,

allow for wound healing, and preserve a functional limb. The final question this updated

guideline seeks to address is whether there is a “best” revascularization strategy to improve

cardiovascular and limb-related outcomes in patients with CLI.

Historically, open surgical revascularization has been recommended for CLI due to better long

term durability and the presumed anatomic complexity of the disease in this population.6, 7, 9 The

rapid evolution of technology over the last decade, however, has led to an “endovascular first”

approach for patients with CLI, even for relatively complicated, diffuse disease.74 Currently,

there is a distinct lack of high quality data to support one approach (endovascular versus open)

over the other.67, 75 The existing studies are overwhelming observational and at risk for bias. The

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial is the only randomized

controlled trial to date to compare open and endovascular procedures in patients with CLI.76

Importantly, this trial was performed when the endovascular group did not include stents or

other adjuncts, and best medical therapy did not reliably include antiplatelet therapy, statins, or

smoking cessation. This may not be reflective of the current state of best medical and

endovascular therapy. It is difficult to compare outcomes between existing studies due to

differences in technique and technologies employed. A systematic review and meta-analysis of

the current literature comparing endovascular and surgical revascularization for CLI suggests no

difference in clinical outcomes between the groups.75 Importantly, several key trials are currently

ongoing that will help address this question in the future.77-79

In the absence of high quality data, the guideline endorses either an endovascular (COR I, LOE

B-R) or surgical (COR I, LOE C-LD) approach to CLI, recognizing that anatomical and patient

factors may influence decision making (Table 5). This is a change from earlier iterations that

generally favored surgery for CLI for any patient with adequate autologous vein conduit and a

life expectancy greater than two years. This recommendation is consistent with TASC II

recommendations that also favor an endovascular approach to most lesions.11 While

endovascular approaches to aortoiliac and femoropopliteal disease have been accepted for

some time, newer advances such as drug eluting stents and balloons are currently

revolutionizing the management of infrapopliteal disease. Meta-analyses of the current literature

found improved wound healing and limb salvage with angiosome-guided therapy for

infrapopliteal lesions, though the quality of the evidence is admittedly low.80, 81

The Interdisciplinary Care Team: Anesthesiologists as Perioperative Medicine Specialists

Caring for patients with PAD, and particularly those with CLI, requires aggressive and

coordinated management of medical comorbidities, wound complications, and procedural

interventions. Interdisciplinary care teams are associated with improved wound healing,

amputation-free survival, and maintenance of ambulatory status for CLI patients compared to

patients receiving standard care.82-84 Regions of the country that provide more intensive

vascular care also have lower amputation rates,85 likely due to improved collaboration and

earlier intervention. This guideline advocates for an interdisciplinary care team to assist in the

evaluation and management of PAD patients and proposes a variety of specialists who should

be involved. It is notable, if unfortunate, that an anesthesiologist specializing in cardiovascular

anesthesiology was omitted from the interdisciplinary care team proposed in this guideline

(Table 6).

Anesthesiologists, as perioperative medicine specialists, are uniquely poised to lead the

interdisciplinary care team in the perioperative period. As a result of the rapid adoption of

endovascular techniques, patients who previously would be considered too high risk for the

operating room are increasingly deemed interventional candidates; and while the intraoperative

anesthetic management of endovascular procedures may be less intensive than their open

counterparts, perioperative care is becoming increasingly complex. Patient with CLI, in

particular, may present with acutely decompensated comorbidities that result in a limited

physiologic reserve. Surgeons and proceduralists may fail to recognize the severity of these

decompensations, or fail to appreciate the importance of targeted optimization prior to urgent,

but not emergent, revascularization. Anesthesiologists, with expertise in both the medical

optimization as well as procedural treatment options for PAD, can serve as a liaison between

the multitude of medical and surgical specialists involved in the care of these patients.

Anesthesiologists, furthermore, are the only physicians whose skill set traverses the entire

spectrum of care: from preoperative medical optimization to postoperative intensive care

management, across traditional operating rooms, hybrid suites, and off-site locations. As such,

the anesthesiologist can offer a “continuity of care” that other specialties cannot provide.

A notable criteria favoring endovascular intervention is the presence of comorbidities that may

place a patient at increased risk of perioperative complications from surgical revascularization,

in whom an endovascular-first approach should be employed regardless of anatomy.8 An

equally important consideration, frequently underappreciated by non-anesthesiologists, is what

sort of anesthetic or sedation technique will be tolerated by the patient. While the majority of

endovascular interventions can be successfully performed under monitored anesthesia care,

CLI patients, in particular, may be poor candidates for sedation due the severity of coexisting

disease or actively decompensated comorbidities. These patients may be exquisitely sensitive

to what would otherwise be considered innocuous doses of sedatives. An inability to lie flat

related to decompensated heart failure, pain control issues related to ongoing ischemia, or

cognitive dysfunction (baseline or delirium) may make it difficult or impossible to cooperate

during the procedure. This may lead to escalating doses of sedation by less experienced

providers, which may not be tolerated due to limited physiologic reserve. General anesthesia

may be considered for these reasons, recognizing that these patients are at elevated risk for

general anesthesia due to advanced medical comorbidities and limited time for perioperative

optimization. Regardless of anesthetic technique employed, these patients are frequently

fragile, with hemodynamics and metabolic derangements that can be labile and difficult to

control. Early engagement of an anesthesiologist may help risk stratify which patients require

the presence of an anesthesiologist, and which patients may safely undergo sedation by a non-

anesthesiologist.

Conclusion

PAD is widely prevalent and associated with significant morbidity and mortality. The natural

history is variable, and it is unclear what the risk factors are for progression to CLI. Aggressive

medical optimization of comorbid conditions and lifestyle interventions are important, although

the optimal treatment strategy, particularly for antiplatelet therapy, has yet to be determined.

Similarly, the optimal revascularization strategy has yet to be determined for both IC and CLI.

There has been a steady trend toward endovascular interventions for PAD, and this trend is

likely to continue in the future as technology and proceduralist skill continues to evolve. There is
limited high quality data to recommend surgical versus endovascular repair, and the “best”

treatment may very well depend on patient and proceduralist factors, as well as technological

and anatomic considerations. Large randomized controlled trials that evaluate different

revascularization techniques will be critical in the future. There is an increasing appreciation for

the importance of a multidisciplinary team who can work together to provide optimal care in this

patient population. The anesthesiologist, with the unique skill set to care for the patient from the

pre- to post-operative period, in a variety of procedural locations, is the obvious choices to lead

this team in the perioperative period. In the coming years, the challenge will be to step up into a

leadership role not just in the operating room, but across the entire scope of perioperative care.

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Table 1. Patients at Increased Risk of PAD

 Age ≥65 years

 Age 50–64 years, with risk factors for ASCVD (e.g., diabetes mellitus, history of
smoking, hyperlipidemia, hypertension) or family history of PAD
 Age <50 years, with diabetes mellitus and 1 additional risk factor for ASCVD
 Individuals with known ASCVD in another vascular bed (e.g., coronary, carotid,
subclavian, renal, mesenteric artery stenosis, or abdominal aortic aneurysm)
ASCVD = atherosclerotic vascular disease; PAD = peripheral artery disease

(Note to publisher: Adapted from Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016
AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery
Disease: A Report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Nov 8. pii: S0735-
1097(16)36902-9. doi: 10.1016/j.jacc.2016.11.007 – permission for use obtained from Copyright
Clearance Center but Elsevier publication)
Table 2. History and/or Physical Examination Findings Suggestive of PAD

History
 Claudication
 Other non-joint related exertional lower extremity symptoms (not typical of
claudication)
 Impaired walking function
 Ischemic rest pain

Physical Examination
 Abnormal lower extremity pulse examination
 Vascular bruit
 Nonhealing lower extremity wound
 Lower extremity gangrene
 Other suggestive lower extremity findings (e.g., elevation pallor/dependent rubor)
PAD = peripheral artery disease

(Note to publisher: Taken from Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016
AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery
Disease: A Report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Nov 8. pii: S0735-
1097(16)36902-9. doi: 10.1016/j.jacc.2016.11.007 – permission for use obtained from Copyright
Clearance Center but Elsevier publication)
Table 3. Behavioral and Lifestyle Recommendations for PAD
6 7
2005 /2011 Recommendations
Patients who are smokers or former
smokers should be asked about
status of tobacco use at every visit
7
(COR I, LOE A)
Patients should be assisted with
counseling and developing a plan for
quitting that may include
pharmacotherapy and/or referral to a
smoking cessation program (COR I,
7
LOE A)
Individuals with lower extremity PAD
who smoke cigarettes or use other
forms of tobacco should be advised
by each of their clinicians to stop
smoking and offered behavioral and
pharmacological treatment (COR I,
7
LOE C)
In the absence of contraindication or
other compelling clinical indication, 1
or more of the following
pharmacological therapies should be
offered: varenicline, bupropion, and
nicotine replacement therapy (COR I,
7
LOE A)
A program of supervised exercise
training is recommended as an initial
treatment modality for patients with
intermittent claudication (COR I, LOE
6
A)
The usefulness of unsupervised
exercise programs is not well
established as an effective initial
treatment modality for patients with
intermittent claudication (COR IIb,
6
LOE B)
8
2016 Updated Recommendations Comment
Patients with PAD who smoke Clarified
cigarettes or use other forms of recommendation
tobacco should be advised at every to emphasize
visit to quit (COR I, LOE A) smoking cessation
counseling at
every visit
Patients with PAD who smoke Combination of
cigarettes should be assisted in previous
developing a plan for quitting that recommendations;
includes pharmacotherapy (i.e., change in level of
varenicline, bupropion, and/or evidence (from C
nicotine replacement therapy) and/or to A)
referral to a smoking cessation
program (COR I, LOE A)
Patients with PAD should avoid New
exposure to environmental tobacco recommendation
smoke at work, at home, and in public
places (COR I, LOE B-NR)
In patients with claudication, a Modification of
supervised exercise program is existing
recommended to improve functional recommendation;
status and quality of life and to reduce change in level of
leg symptoms (COR I, LOE A) evidence (from A
to B-R)
A supervised exercise program should
be discussed as a treatment option for
claudication before possible
revascularization (COR I, LOE B-R)
In patients with PAD, a structured New
community- or home-based exercise recommendation
program with behavioral change regarding
techniques can be beneficial to structured, but
improve walking ability and functional unsupervised,
status (COR IIa, LOE A) exercise programs
In patients with claudication, New
alternative strategies of exercise recommendation
therapy, including upper-body
ergometry, cycling, and pain-free or
low-intensity walking that avoids
 moderate-to-maximum claudication
while walking, can be beneficial to
improve walking ability and functional
status (COR IIa, LOE A)

COR = class of recommendation; LOE = level of evidence; PAD = peripheral artery disease;

Table 4. Management of Antiplatelet Agents for PAD

2016 Updated
2011 Recommendations7 Comment
Recommendations8
Antiplatelet therapy is indicated to reduce Antiplatelet therapy with Modified (wording
the risk of MI, stroke, and vascular death aspirin alone (75–325 mg clarified) and
in individuals with symptomatic PAD, per day) or clopidogrel combined
including those with IC or CLI, prior to alone (75 mg per day) is recommendations;
lower extremity revascularization or recommended to reduce change in level of
amputation (COR I, LOE A) MI, stroke, and vascular evidence for
death in patients with individual drugs
Aspirin, typically in daily doses of 75 to symptomatic PAD (COR I, (from B to A)
325 mg, is recommended as safe and LOE A)
effective antiplatelet therapy to reduce the
risk of MI, stroke, and vascular death in
individuals with symptomatic PAD,
including those with IC or CLI, prior to
lower extremity revascularization
(endovascular or surgical), or prior to
amputation for lower extremity ischemia
(COR 1, LOE B)

Clopidogrel (75 mg) is recommended as

safe and effective alternative antiplatelet
therapy to reduce the risk of MI, stroke,
and vascular death in individuals with
symptomatic PAD, including those with IC
or CLI, prior to lower extremity
revascularization (endovascular or
surgical), or prior to amputation for lower
extremity ischemia (COR 1, LOE B)
Antiplatelet therapy can be useful to In asymptomatic patients Modified
reduce the risk of MI, stroke, or vascular with PAD (ABI ≤0.90), recommendation
death in asymptomatic individuals with an antiplatelet therapy is (clarified wording);
ABI less than or equal to 0.90 (Class IIa, reasonable to reduce the clarification of level
LOE C) risk of MI, stroke, or of evidence to
vascular death (COR IIa, reflect expert
LOE C-EO) opinion
The usefulness of antiplatelet therapy to In asymptomatic patients Modified
reduce the risk of MI, stroke, or vascular with borderline ABI (0.91– recommendation
death in asymptomatic individuals with 0.99), the usefulness of (clarified wording);
borderline abnormal ABI, defined as 0.91 antiplatelet therapy to change in level of
to 0.99, is not well established (Class IIb, reduce the risk of MI, evidence (from A to
LOE A) stroke, or vascular death is B-R)
uncertain (COR IIb, LOE
B-R)
The combination of aspirin and The effectiveness DAPT Modified
clopidogrel may be considered to reduce (aspirin and clopidogrel) to recommendation
the risk of cardiovascular events in reduce the risk of (clarified wording);
patients with symptomatic atherosclerotic cardiovascular ischemic clarification of level
lower extremity PAD, including those with events in patients with of evidence to
IC or CLI, prior to lower extremity symptomatic PAD is not reflect randomized
revascularization (endovascular or well established (COR IIb, trials
surgical), or prior to amputation for lower LOE B-R)
extremity ischemia and who are not at
increased risk of bleeding and who are at
high perceived cardiovascular risk (COR
IIb, LOE B)
DAPT may be reasonable New
to reduce the risk of limb recommendation
related events in patients
with symptomatic PAD
after lower extremity
revascularization (COR IIb,
LOE C-LD)
The overall clinical benefit New
of vorapaxar added to recommendation
existing antiplatelet
therapy in patients with
symptomatic PAD is
uncertain (COR IIb, LOE
B-R)

COR = class of recommendation; LOE = level of evidence; MI = myocardial infarction; PAD =

peripheral artery disease; IC = intermittent claudication; CLI = critical limb ischemia; ABI = ankle
brachial index; DAPT = dual antiplatelet therapy
Table 5. Therapy for CLI: Findings that Prompt Consideration of Surgical or
Endovascular Revascularization
Findings Favoring Surgical
Revascularization
Factors associated with poor durability or
technical failure of endovascular treatment
Endovascular treatment likely to preclude or
complicate subsequent achievement of in-line
blood flow via surgical revascularization
Findings Favoring Endovascular
Revascularization
The presence of patient comorbidities may
place patients at increased risk of
perioperative complications from surgical
revascularization. In these patients, an
endovascular-first approach should be used
regardless of anatomy
Patients with rest pain and disease at
multiple levels may undergo a staged
approach as part of endovascular-first
approach
Patients without suitable autologous vein for
bypass grafts
Example
Common femoral artery lesions
Long segment lesion involving below-knee
popliteal and/or infrapopliteal arteries in a
patient with suitable single-segment
autogenous vein conduit
Diffuse multilevel disease that would require
endovascular revascularization at multiple
anatomic levels
Small-diameter target artery proximal to site
of stenosis or densely calcified lesion at
location of endovascular treatment
Single-vessel runoff distal to ankle
Example
coronary ischemia, cardiomyopathy,
congestive heart failure, severe lung disease,
and chronic kidney disease
In-flow disease may be addressed first out-
flow disease addressed in a staged manner,
if/when required, if clinical factors or patient
safety prevent addressing all diseased
segments at one setting
Previous vein harvest for coronary artery
bypass surgery and no adequate remaining
veins for conduits; available vein of
inadequate diameter

(Note to publisher: Taken from Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016
AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery
Disease: A Report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Nov 8. pii: S0735-
1097(16)36902-9. doi: 10.1016/j.jacc.2016.11.007 – permission for use obtained from Copyright
Clearance Center but Elsevier publication)
Table 6. Interdisciplinary Care Team for PAD

A team of professionals representing different disciplines to assist in the evaluation and

management of the patient with PAD. For the care of patients with CLI, the interdisciplinary
care team should include individuals who are skilled in endovascular revascularization,
surgical revascularization, wound healing therapies and foot surgery, and medical evaluation
and care.

Interdisciplinary care team members may include:

 Vascular medical and surgical specialists (ie, vascular medicine, vascular surgery,
interventional radiology, interventional cardiology)
 Nurses
 Orthopedic surgeons and podiatrists
 Endocrinologists
 Internal medicine specialists
 Infectious disease specialists
 Radiology and vascular imaging specialists
 Physical medicine and rehabilitation clinicians
 Orthotics and prosthetics specialists
 Social workers
 Exercise physiologists
 Physical and occupational therapists
 Nutritionists/dieticians
PAD = peripheral artery disease; CLI = critical limb ischemia
(Note to publisher: Taken from Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016
AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery
Disease: A Report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Nov 8. pii: S0735-
1097(16)36902-9. doi: 10.1016/j.jacc.2016.11.007 – permission for use obtained from Copyright
Clearance Center but Elsevier publication)