2016 Acc Pad
2016 Acc Pad
2016 Acc Pad
PII: S0735-1097(16)36902-9
DOI: 10.1016/j.jacc.2016.11.007
Reference: JAC 23164
Please cite this article as: Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA,
Drachman DE, Fleisher LA, Fowkes FGR, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L,
Olin JW, Patel RAG, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D,
Walsh ME, 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral
Artery Disease, Journal of the American College of Cardiology (2016), doi: 10.1016/j.jacc.2016.11.007.
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Gerhard-Herman MD, et al.
2016 AHA/ACC Lower Extremity PAD Guideline
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Developed in Collaboration With the American Association of Cardiovascular and Pulmonary
Rehabilitation, Inter-Society Consensus for the Management of Peripheral Arterial Disease, Society for
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Cardiovascular Angiography and Interventions, Society for Clinical Vascular Surgery, Society of
Interventional Radiology, Society for Vascular Medicine, Society for Vascular Nursing, Society for
Vascular Surgery, and Vascular and Endovascular Surgery Society
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WRITING COMMITTEE MEMBERS*
Marie D. Gerhard-Herman, MD, FACC, FAHA, Chair
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Heather L. Gornik, MD, FACC, FAHA, FSVM, Vice Chair*
Coletta Barrett, RN Leila Mureebe, MD, MPH, RPVI
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Neal R. Barshes, MD, MPH Jeffrey W. Olin, DO, FACC, FAHA*
Matthew A. Corriere, MD, MS, FAHA Rajan A. G. Patel, MD, FACC, FAHA, FSCAI#
Douglas E. Drachman, MD, FACC, FSCAI* Judith G. Regensteiner, PhD, FAHA
Lee A. Fleisher, MD, FACC, FAHA Andres Schanzer, MD*
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Francis Gerry R. Fowkes, MD, FAHA*# Mehdi H. Shishehbor, DO, MPH, PhD, FACC, FAHA, FSCAI *
Naomi M. Hamburg, MD, FACC, FAHA Kerry J. Stewart, EdD, FAHA, MAACVPR
Scott Kinlay, MBBS, PhD, FACC, FAHA, FSVM, FSCAI* ** Diane Treat-Jacobson, PhD, RN, FAHA
Robert Lookstein, MD, FAHA, FSIR* M. Eileen Walsh, PhD, APN, RN-BC, FAHA
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*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with
industry and other entities may apply; see Appendix 1 for recusal information. Functioning as the lay volunteer/patient representative.
ACC/AHA Representative. Vascular and Endovascular Surgery Society Representative. Society for Cardiovascular Angiography and
Interventions Representative. ACC/AHA Task Force on Clinical Practice Guidelines Liaison. #Inter-Society Consensus for the
Management of Peripheral Arterial Disease Representative. **Society for Vascular Medicine Representative. Society of Interventional
Radiology Representative. Society for Clinical Vascular Surgery Representative. Society for Vascular Surgery Representative.
American Association of Cardiovascular and Pulmonary Rehabilitation Representative. Society for Vascular Nursing
Representative.
This document was approved by the American College of Cardiology Board of Trustees in October 2016, the American Heart
Association Science Advisory and Coordinating Committee in September 2016, and the American Heart Association Executive
Committee in October 2016.
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 1
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2016 AHA/ACC Lower Extremity PAD Guideline
The American College of Cardiology requests that this document be cited as follows: Gerhard-Herman MD, Gornik HL, Barrett C,
Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FGR, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin
JW, Patel RAG, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 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;XX:xxx-xx.
This article has been copublished in Circulation and reprinted in Vascular Medicine.
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Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org) and the
American Heart Association (professional.heart.org). For copies of this document, please contact Elsevier Inc. Reprint Department via
fax (212-633-3820) or e-mail (reprints@elsevier.com).
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Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the
express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site
(http://www.elsevier.com/about/policies/author-agreement/obtaining-permission).
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2016 by the American Heart Association, Inc. and American College of Cardiology Foundation.
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Table of Contents
Preamble................................................................................................................................................................................... 4
1. Introduction......................................................................................................................................................................... 8
1.1. Methodology and Evidence Review ............................................................................................................. 8
1.2. Organization of the Writing Committee........................................................................................................ 9
1.3. Document Review and Approval ................................................................................................................. 9
1.4. Scope of Guideline .................................................................................................................................. 10
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2. Clinical Assessment for PAD ........................................................................................................................................... 14
2.1. History and Physical Examination: Recommendations ................................................................................. 14
3. Diagnostic Testing for the Patient With Suspected Lower Extremity PAD (Claudication or CLI) .................................. 16
3.1. Resting ABI for Diagnosing PAD: Recommendations .................................................................................. 16
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3.2. Physiological Testing: Recommendations ................................................................................................... 17
3.3. Imaging for Anatomic Assessment: Recommendations................................................................................. 24
4. Screening for Atherosclerotic Disease in Other Vascular Beds for the Patient With PAD .............................................. 25
4.1. Abdominal Aortic Aneurysm: Recommendation.......................................................................................... 25
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4.2. Screening for Asymptomatic Atherosclerosis in Other Arterial Beds (Coronary, Carotid, and Renal Arteries) ...... 25
5. Medical Therapy for the Patient With PAD ...................................................................................................................... 26
5.1. Antiplatelet Agents: Recommendations ...................................................................................................... 26
5.2. Statin Agents: Recommendation ............................................................................................................... 28
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5.3. Antihypertensive Agents: Recommendations .............................................................................................. 29
5.4. Smoking Cessation: Recommendations ...................................................................................................... 29
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5.5. Glycemic Control: Recommendations ........................................................................................................ 30
5.6. Oral Anticoagulation: Recommendations ................................................................................................... 31
5.7. Cilostazol: Recommendation .................................................................................................................... 32
5.8. Pentoxifylline: Recommendation............................................................................................................... 32
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Preamble
Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have
translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular
health. These guidelines, based on systematic methods to evaluate and classify evidence, provide a cornerstone
of quality cardiovascular care.
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In response to reports from the Institute of Medicine (1, 2) and a mandate to evaluate new knowledge
and maintain relevance at the point of care, the ACC/AHA Task Force on Clinical Practice Guidelines (Task
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Force) modified its methodology (3-5). The relationships among guidelines, data standards, appropriate use
criteria, and performance measures are addressed elsewhere (5).
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Intended Use
Practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular
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disease. The focus is on medical practice in the United States, but guidelines developed in collaboration with
other organizations may have a broader target. Although guidelines may be used to inform regulatory or payer
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decisions, the intent is to improve quality of care and align with patients interests. Guidelines are intended to
define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical
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judgment. Guidelines are reviewed annually by the Task Force and are official policy of the ACC and AHA.
Each guideline is considered current until it is updated, revised, or superseded by published addenda, statements
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of clarification, focused updates, or revised full-text guidelines. To ensure that guidelines remain current, new
data are reviewed biannually to determine whether recommendations should be modified. In general, full
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Modernization
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Processes have evolved to support the evolution of guidelines as living documents that can be dynamically
updated. This process delineates a recommendation to address a specific clinical question, followed by concise
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text (ideally <250 words) and hyperlinked to supportive evidence. This approach accommodates time constraints
on busy clinicians and facilitates easier access to recommendations via electronic search engines and other
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evolving technology.
Evidence Review
Writing committee members review the literature; weigh the quality of evidence for or against particular tests,
treatments, or procedures; and estimate expected health outcomes. In developing recommendations, the writing
committee uses evidence-based methodologies that are based on all available data (3-7). Literature searches
focus on randomized controlled trials (RCTs) but also include registries, nonrandomized comparative and
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descriptive studies, case series, cohort studies, systematic reviews, and expert opinion. Only selected references
are cited.
The Task Force recognizes the need for objective, independent Evidence Review Committees (ERCs)
that include methodologists, epidemiologists, clinicians, and biostatisticians who systematically survey, abstract,
and assess the evidence to address systematic review questions posed in the PICOTS format (P=population,
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I=intervention, C=comparator, O=outcome, T=timing, S=setting) (2, 4-6). Practical considerations, including
time and resource constraints, limit the ERCs to evidence that is relevant to key clinical questions and lends
itself to systematic review and analysis that could affect the strength of corresponding recommendations.
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Recommendations developed by the writing committee on the basis of the systematic review are marked SR.
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Guideline-Directed Management and Treatment
The term guideline-directed management and therapy (GDMT) refers to care defined mainly by ACC/AHA
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Class I recommendations. For these and all recommended drug treatment regimens, the reader should confirm
dosage with product insert material and carefully evaluate for contraindications and interactions.
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Recommendations are limited to treatments, drugs, and devices approved for clinical use in the United States.
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the effect of the intervention on the basis of the type, quality, quantity, and consistency of data from clinical
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trials and other reports (Table 1) (3-5). Unless otherwise stated, recommendations are sequenced by COR and
then by LOE. Where comparative data exist, preferred strategies take precedence. When >1 drug, strategy, or
therapy exists within the same COR and LOE and no comparative data are available, options are listed
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alphabetically.
The ACC and AHA sponsor the guidelines without commercial support, and members volunteer their time. The
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Task Force zealously avoids actual, potential, or perceived conflicts of interest that might arise through
relationships with industry or other entities (RWI). All writing committee members and reviewers are required
to disclose current industry relationships or personal interests, from 12 months before initiation of the writing
effort. Management of RWI involves selecting a balanced writing committee and assuring that the chair and a
majority of committee members have no relevant RWI (Appendix 1). Members are restricted with regard to
writing or voting on sections to which their RWI apply. For transparency, members comprehensive disclosure
information is available online (http://jaccjacc.acc.org/Clinical_Document/2016_LEPAD_Guideline_RWI.pdf).
Comprehensive disclosure information for the Task Force is also available at
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http://www.acc.org/guidelines/about-guidelines-and-clinical-documents/guidelines-and-documents-task-forces.
The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing
different geographic regions, sexes, ethnicities, intellectual perspectives/biases, and scopes of clinical practice,
and by inviting organizations and professional societies with related interests and expertise to participate as
partners or collaborators.
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Individualizing Care in Patients With Associated Conditions and Comorbidities
Managing patients with multiple conditions can be complex, especially when recommendations applicable to
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coexisting illnesses are discordant or interacting (8). The guidelines are intended to define practices meeting the
needs of patients in most, but not all, circumstances. The recommendations should not replace clinical judgment.
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Clinical Implementation
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Management in accordance with guideline recommendations is effective only when followed. Adherence to
recommendations can be enhanced by shared decision making between clinicians and patients, with patient
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engagement in selecting interventions on the basis of individual values, preferences, and associated conditions
and comorbidities. Consequently, circumstances may arise in which deviations from these guidelines are
appropriate.
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Table 1. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions,
Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015)
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1. Introduction
1.1. Methodology and Evidence Review
The recommendations listed in this guideline are, whenever possible, evidence based. An initial extensive
evidence review, which included literature derived from research involving human subjects, published in
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English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for
Healthcare Research and Quality, and other selected databases relevant to this guideline, was conducted from
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January through September 2015. Key search words included but were not limited to the following: acute limb
ischemia, angioplasty, ankle-brachial index, anticoagulation, antiplatelet therapy, atypical leg symptoms, blood
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pressure lowering/hypertension, bypass graft/bypass grafting/surgical bypass, cilostazol,
claudication/intermittent claudication, critical limb ischemia/severe limb ischemia, diabetes, diagnostic testing,
endovascular therapy, exercise rehabilitation/exercise therapy/exercise training/supervised exercise, lower
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extremity/foot wound/ulcer, peripheral artery disease/peripheral arterial disease/peripheral vascular
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disease/lower extremity arterial disease, smoking/smoking cessation, statin, stenting, and vascular surgery.
Additional relevant studies published through September 2016, during the guideline writing process, were also
considered by the writing committee, and added to the evidence tables when appropriate. The final evidence
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utilized by the writing committee to formulate recommendations. Additionally, the writing committee reviewed
documents related to lower extremity peripheral artery disease (PAD) previously published by the ACC and
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AHA (9, 10). References selected and published in this document are representative and not all-inclusive.
As stated in the Preamble, the ACC/AHA guideline methodology provides for commissioning an
independent ERC to address systematic review questions (PICOTS format) to inform recommendations
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developed by the writing committee. All other guideline recommendations (not based on the systematic review
questions) were also subjected to an extensive evidence review process. For this guideline, the writing
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committee in conjunction with the Task Force and ERC Chair identified the following systematic review
questions: 1) Is antiplatelet therapy beneficial for prevention of cardiovascular events in the patient with
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symptomatic or asymptomatic lower extremity PAD? 2) What is the effect of revascularization, compared with
optimal medical therapy and exercise training, on functional outcome and quality of life (QoL) among patients
with claudication? Each question has been the subject of recently published, systematic evidence reviews (11-
13). The quality of these evidence reviews was appraised by the ACC/AHA methodologist and a vendor
contracted to support this process (Doctor Evidence [Santa Monica, CA]). Few substantive randomized or
nonrandomized studies had been published after the end date of the literature searches used for the existing
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evidence reviews, so the ERC concluded that no additional systematic review was necessary to address either of
these critical questions.
A third systematic review question was then identified: 3) Is one revascularization strategy
(endovascular or surgical) associated with improved cardiovascular and limb-related outcomes in patients with
critical limb ischemia (CLI)? This question had also been the subject of a high-quality systematic review that
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synthesized evidence from observational data and an RCT (14); additional RCTs addressing this question are
ongoing (15-17). The writing committee and the Task Force decided to expand the survey to include more
relevant randomized and observational studies. Based on evaluation of this additional evidence the ERC decided
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that further systematic review was not needed to inform the writing committee on this question. Hence, the ERC
and writing committee concluded that available systematic reviews could be used to inform the development of
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recommendations addressing each of the 3 systematic review questions specified above. The members of the
Task Force and writing committee thank the members of the ERC that began this process and their willingness
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to participate in this volunteer effort. They include Aruna Pradhan, MD, MPH (ERC Chair); Natalie Evans, MD;
Peter Henke, MD; Dharam J. Kumbhani, MD, SM, FACC; and Tamar Polonsky, MD.
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1.2. Organization of the Writing Committee
The writing committee consisted of clinicians, including noninvasive and interventional cardiologists, exercise
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physiologists, internists, interventional radiologists, vascular nurses, vascular medicine specialists, and vascular
surgeons, as well as clinical researchers in the field of vascular disease, a nurse (in the role of patient
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representative), and members with experience in epidemiology and/or health services research. The writing
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committee included representatives from the ACC and AHA, American Association of Cardiovascular and
Pulmonary Rehabilitation, Inter-Society Consensus for the Management of Peripheral Arterial Disease, Society
for Cardiovascular Angiography and Interventions, Society for Clinical Vascular Surgery, Society of
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Interventional Radiology, Society for Vascular Medicine, Society for Vascular Nursing, Society for Vascular
Surgery, and Vascular and Endovascular Surgery Society.
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This document was reviewed by 2 official reviewers nominated by the ACC and AHA; 1 to 2 reviewers each
from the American Association of Cardiovascular and Pulmonary Rehabilitation, Inter-Society Consensus for
the Management of Peripheral Arterial Disease, Society for Cardiovascular Angiography and Interventions,
Society for Clinical Vascular Surgery, Society of Interventional Radiology, Society for Vascular Medicine,
Society for Vascular Nursing, Society for Vascular Surgery, and Vascular and Endovascular Surgery Society;
and 16 additional individual content reviewers. Reviewers RWI information was distributed to the writing
committee and is published in this document (Appendix 2).
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This document was approved for publication by the governing bodies of the ACC and the AHA and
endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, Inter-Society
Consensus for the Management of Peripheral Arterial Disease, Society for Cardiovascular Angiography and
Interventions, Society for Clinical Vascular Surgery, Society of Interventional Radiology, Society for Vascular
Medicine, Society for Vascular Nursing, Society for Vascular Surgery, and Vascular and Endovascular Surgery
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Society.
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Lower extremity PAD is a common cardiovascular disease that is estimated to affect approximately 8.5 million
Americans above the age of 40 years and is associated with significant morbidity, mortality, and QoL
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impairment (18). It has been estimated that 202 million people worldwide have PAD (19). The purpose of this
document is to provide a contemporary guideline for diagnosis and management of patients with lower
extremity PAD. This document supersedes recommendations related to lower extremity PAD in the ACC/AHA
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2005 Guidelines for the Management of Patients With Peripheral Arterial Disease (9) and the 2011
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ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease
(10). The scope of this guideline is limited to atherosclerotic disease of the lower extremity arteries (PAD) and
includes disease of the aortoiliac, femoropopliteal, and infrapopliteal arterial segments. It does not address
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nonatherosclerotic causes of lower extremity arterial disease, such as vasculitis, fibromuscular dysplasia,
physiological entrapment syndromes, cystic adventitial disease, and other entities. Future guidelines will address
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aneurysmal disease of the abdominal aorta and lower extremity arteries and diseases of the renal and mesenteric
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arteries.
In developing the 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity
Peripheral Artery Disease, the writing committee reviewed the evidence to support recommendations in the
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relevant ACC/AHA guidelines noted in Table 2 and affirms the ongoing validity of the related
recommendations, thus obviating the need to repeat existing guideline recommendations in the current
guideline. Table 2 also contains a list of other statements that may be of interest to the reader. Table 3 includes
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undergoing noncardiac surgery
Lifestyle management to reduce cardiovascular risk AHA/ACC 2013 (22)
Assessment of cardiovascular risk ACC/AHA 2013 (23)
Blood cholesterol to reduce atherosclerotic cardiovascular risk in
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ACC/AHA 2013 (24)
adults
Peripheral arterial disease (lower extremity, renal, mesenteric, and 2005 (9) and
ACC/AHA
abdominal aortic) 2011 (10)
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Secondary prevention and risk-reduction therapy for patients with
AHA/ACC 2011 (25)
coronary and other atherosclerotic vascular disease
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Atherosclerotic occlusive disease of the lower extremities guideline SVS 2015 (26)
Measurement and interpretation of the ankle-brachial index AHA 2012 (27)
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Cardiac disease evaluation and management among kidney and liver
AHA/ACC 2012 (28)
transplantation candidates
Intensive glycemic control and the prevention of cardiovascular
ADA/ACC/AHA 2009 (29)
events
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arteriography KCVD
Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure (JNC NHLBI 2003 (32)
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7)*
*A revision to the current document is being prepared, with publication expected in 2017. The new title is expected to be
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Detection, Evaluation,
Prevention and Management of High Blood Pressure.
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AAPA indicates American Academy of Physician Assistants; ABC, Association of Black Cardiologists; ACC, American
College of Cardiology; ACPM, American College of Preventive Medicine; ADA, American Diabetes Association; AGS,
American Geriatrics Society; AHA, American Heart Association; APhA, American Pharmacists Association; ASH,
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American Society of Hypertension; ASPC, American Society for Preventive Cardiology; CLCD, Council on Clinical
Cardiology; CVRI, Council on Cardiovascular Radiology and Intervention; KCVD, Council on Kidney in Cardiovascular
Disease; NHLBI, National Heart, Lung, and Blood Institute; NMA, National Medical Association; PAD, peripheral artery
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disease; PCNA, Preventive Cardiovascular Nurses Association; and SVS, Society for Vascular Surgery.
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I. ViableLimb is not immediately threatened; no sensory loss; no muscle
weakness; audible arterial and venous Doppler.
II. ThreatenedMild-to-moderate sensory or motor loss; inaudible arterial
Doppler; audible venous Doppler; may be further divided into IIa
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(marginally threatened) or IIb (immediately threatened).
III. IrreversibleMajor tissue loss or permanent nerve damage inevitable;
profound sensory loss, anesthetic; profound muscle weakness or paralysis
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(rigor); inaudible arterial and venous Doppler (33, 34).
Tissue loss Type of tissue loss:
Minornonhealing ulcer, focal gangrene with diffuse pedal ischemia.
Majorextending above transmetatarsal level; functional foot no longer
salvageable (33).
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Critical limb ischemia (CLI) A condition characterized by chronic (2 wk) ischemic rest pain, nonhealing
wound/ulcers, or gangrene in 1 or both legs attributable to objectively proven arterial
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occlusive disease.
The diagnosis of CLI is a constellation of both symptoms and signs. Arterial
disease can be proved objectively with ABI, TBI, TcPO2, or skin perfusion
pressure. Supplementary parameters, such as absolute ankle and toe pressures and
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pulse volume recordings, may also be used to assess for significant arterial
occlusive disease. However, a very low ABI or TBI does not necessarily mean the
patient has CLI. The term CLI implies chronicity and is to be distinguished from
ALI (35).
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In-line blood flow Direct arterial flow to the foot, excluding collaterals.
Functional status Patients ability to perform normal daily activities required to meet basic needs, fulfill
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usual roles, and maintain health and well-being. Walking ability is a component of
functional status.
Nonviable limb Condition of extremity (or portion of extremity) in which loss of motor function,
neurological function, and tissue integrity cannot be restored with treatment.
Salvageable limb Condition of extremity with potential to secure viability and preserve motor function to
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There are 2 types of structured exercise program for patients with PAD:
1. Supervised exercise program
2. Structured community- or home-based exercise program
Supervised exercise program Structured exercise program that takes place in a hospital or outpatient facility in which
intermittent walking exercise is used as the treatment modality.
Program can be standalone or can be made available within a cardiac
rehabilitation program.
Program is directly supervised by qualified healthcare provider(s).
Training is performed for a minimum of 30 to 45 min per session, in sessions
performed at least 3 times/wk for a minimum of 12 wk (36-46). Patients may not
initially achieve these targets, and a treatment goal is to progress to these levels
over time.
Training involves intermittent bouts of walking to moderate-to-maximum
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Term Definition
claudication, alternating with periods of rest.
Warm-up and cool-down periods precede and follow each session of walking.
Structured community- or home- Structured exercise program that takes place in the personal setting of the patient rather
based exercise program than in a clinical setting (41, 47-51).
Program is self-directed with the guidance of healthcare providers who prescribe
an exercise regimen similar to that of a supervised program.
Patient counseling ensures that patients understand how to begin the program,
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how to maintain the program, and how to progress the difficulty of the walking
(by increasing distance or speed).
Program may incorporate behavioral change techniques, such as health coaching
and/or use of activity monitors.
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Emergency versus urgent An emergency procedure is one in which life or limb is threatened if the patient is
not in the operating room or interventional suite and/or where there is time for no
or very limited clinical evaluation, typically within <6 h.
An urgent procedure is one in which there may be time for a limited clinical
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evaluation, usually when life or limb is threatened if the patient is not in the
operating room or interventional suite, typically between 6 and 24 h.
Interdisciplinary care team A team of professionals representing different disciplines to assist in the evaluation and
management of the patient with PAD.
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For the care of patients with CLI, the interdisciplinary care team should include
individuals who are skilled in endovascular revascularization, surgical
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revascularization, wound healing therapies and foot surgery, and medical
evaluation and care.
Interdisciplinary care team members may include:
o Vascular medical and surgical specialists (i.e., vascular medicine,
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ischemic amputation.
ABI indicates ankle-brachial index; ALI, acute limb ischemia; CLI, critical limb ischemia; MI, myocardial infarction; PAD,
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peripheral artery disease; TBI, toe-brachial index; and TcPO2, transcutaneous oxygen pressure.
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Recommendations for History and Physical Examination
COR LOE Recommendations
Patients at increased risk of PAD (Table 4) should undergo a comprehensive
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I B-NR medical history and a review of symptoms to assess for exertional leg
symptoms, including claudication or other walking impairment, ischemic
rest pain, and nonhealing wounds (52-57).
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The symptoms and signs of PAD are variable. Patients with PAD may
experience the classic symptom of claudication or may present with advanced
disease, including CLI. Studies have demonstrated that the majority of patients
with confirmed PAD do not have typical claudication but have other nonjoint-
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related limb symptoms or are asymptomatic (53, 55). Atypical lower extremity
symptoms related to PAD may include pain or discomfort that begins at rest but
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See Online Data
worsens with exertion, pain or discomfort that does not stop an individual from
Supplement 1.
walking, and pain or discomfort that begins with exertion but is not alleviated
within 10 minutes of rest (54). Patients with PAD who do not have typical
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claudication but have other leg symptoms, or who are asymptomatic, have been
shown to have functional impairment comparable to patients with claudication
(54). Thus, all patients at increased risk of PAD should be asked not only about
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claudication but also about other exertional nonjoint-related limb symptoms and
perceived walking impairment.
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2016 AHA/ACC Lower Extremity PAD Guideline
and absence of bruits decreases the likelihood of confirmed PAD (56, 58). The
presence of nonhealing lower extremity wounds may be a sign of CLI. Findings
of cool or discolored skin and delayed capillary refill are not reliable for PAD
diagnosis (56). To confirm the diagnosis of PAD, abnormal physical examination
findings must be confirmed with diagnostic testing (Section 3), generally with
the ABI as the initial test.
PT
Patients with PAD should undergo noninvasive blood pressure
I B-NR measurement in both arms at least once during the initial assessment (60-
62).
An inter-arm blood pressure difference of >15 to 20 mm Hg is abnormal and
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suggestive of subclavian (or innominate) artery stenosis. Patients with PAD are
at increased risk of subclavian artery stenosis (60-62). Measuring blood pressure
in both arms identifies the arm with the highest systolic pressure, a requirement
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for accurate measurement of the ABI (27). Identification of unequal blood
See Online Data
pressures in the arms also allows for more accurate measurement of blood
Supplement 1
pressure in the treatment of hypertension (i.e., blood pressure is taken at the arm
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with higher measurements). Although a difference in arm systolic pressures of
>15 to 20 mm Hg suggests subclavian (or innominate) artery stenosis, in the
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absence of symptoms (e.g., arm claudication or symptoms of vertebral artery
steal), no further imaging or intervention is warranted.
Table 4. Patients at Increased Risk of PAD
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Age 65 y
Age 5064 y, with risk factors for atherosclerosis (e.g., diabetes mellitus, history of smoking,
hyperlipidemia, hypertension) or family history of PAD (63)
Age <50 y, with diabetes mellitus and 1 additional risk factor for atherosclerosis
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Individuals with known atherosclerotic disease in another vascular bed (e.g., coronary, carotid,
subclavian, renal, mesenteric artery stenosis, or AAA)
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Claudication
Other nonjoint-related exertional lower extremity symptoms (not typical of claudication)
Impaired walking function
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COR LOE Recommendations
In patients with history or physical examination findings suggestive of PAD
I B-NR (Table 5), the resting ABI, with or without segmental pressures and
waveforms, is recommended to establish the diagnosis (64-69).
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The resting ABI is obtained by measuring systolic blood pressures at the arms
(brachial arteries) and ankles (dorsalis pedis and posterior tibial arteries) in the
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supine position by using a Doppler device. The ABI of each leg is calculated by
dividing the higher of the dorsalis pedis or posterior tibial pressure by the higher
of the right or left arm blood pressure (27). In patients with a history or physical
See Online Data examination suggestive of PAD, the ABI has good validity as a first-line test in
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the diagnosis of PAD, as shown by vascular imaging, with sensitivities ranging
from 68% to 84% and specificities from 84% to 99% (64-69). Segmental lower
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extremity blood pressures and Doppler or plethysmographic waveforms (pulse
volume recordings) can be used to localize anatomic segments of disease (e.g.,
aortoiliac, femoropopliteal, infrapopliteal) (34, 70, 71).
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0.90 are diagnosed with PAD (67-69). Those with ABI 0.91 to 0.99 may
possibly have PAD and should undergo exercise ABI, if the clinical suspicion of
PAD is significant (Tables 4 and 5) (73, 74). Values >1.40 indicate that the
See Online Data arteries were not able to be compressed, which is more common among
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Supplement 4.
individuals with diabetes mellitus and/or advanced chronic kidney disease. In the
setting of noncompressible ABI values, additional imaging can be used to
diagnose PAD if the clinical suspicion is significant (Figures 1 and 2) (72).
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These cutpoints for ABI interpretation have been previously proposed and
represent a reasonable standardized categorization (27).
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2016 AHA/ACC Lower Extremity PAD Guideline
PT
shown to be associated with improvement in functional status in patients with
asymptomatic PAD (93, 94), the benefit of resting ABI testing to identify
asymptomatic patients who are at increased risk of functional decline and may
benefit from structured exercise programs remains to be determined.
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In patients not at increased risk of PAD (Table 4) and without history or
III: No physical examination findings suggestive of PAD (Table 5), the ABI is not
B-NR
Benefit
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recommended (95, 98).
The prevalence of PAD among individuals without risk factors for
atherosclerosis and who are <50 years of age is low. Data from population-based
cohort studies have demonstrated a low prevalence (approximately 1%) of
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abnormal resting ABI among individuals <50 years of age (95, 98). In the
See Online Data NHANES (National Health and Nutrition Study), approximately 95% of
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Supplement 4.
participants with an abnormal resting ABI had at least 1 risk factor for
atherosclerosis (95). The yield of ABI testing among younger, asymptomatic
individuals without risk factors for atherosclerosis is low, and these patients
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noncompressible arteries, which cause an artificial elevation of the ABI (99, 100,
102, 103). A TBI 0.70 is abnormal and diagnostic of PAD because the digital
arteries are rarely noncompressible (99-102, 104, 105). Patients with
See Online Data
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PT
IIa B-NR treadmill ABI testing can be useful to objectively assess functional status
(71, 74, 107-110).
In patients with PAD, exercise treadmill ABI testing can objectively assess
symptoms, measure change in ABI in response to exercise, and assess functional
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status (71, 74, 107-110) (Figure 1). It can be useful to correlate exertional lower
extremity symptoms to a decline in ABI after treadmill exercise. Exercise
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treadmill ABI testing can document the magnitude of symptom limitation in
patients with PAD and provide objective data that can demonstrate the safety of
See Online Data
exercise and help to individualize exercise prescriptions in patients with PAD
Supplement 5.
before initiation of a formal program of structured exercise training. Exercise
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ABI may also be used to objectively measure the functional improvement
obtained in response to claudication treatment (e.g., structured exercise program
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or revascularization). Administration of a 6-minute walk test in a corridor is a
reasonable alternative to treadmill ABI testing for assessment of functional status
(54).
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patients with diabetes mellitus and a nonhealing wound (Figure 2) (115, 116). A
TBI 0.70 is considered diagnostic of PAD (101, 104, 105). Doppler or
plethysmographic waveforms taken at the toe supplement the toe pressure and
TBI measurement and may be severely dampened in the setting of CLI. The
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cold. TcPO2 measurements are performed with a standardized protocol and are
taken at multiple sites (117). Correlation between TBI, TcPO2, and SPP has been
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reported (113). TcPO2 >30 mm Hg has been used to predict ulcer healing (118).
SPP 30 to 50 mm Hg is associated with increased likelihood of wound healing
(113). If perfusion measures are normal or only mildly impaired, alternative
causes of the nonhealing wounds are considered (Table 7). TcPO2 and SPP can
be used in angiosome-targeted assessment for revascularization (119).
In patients with PAD with an abnormal ABI (0.90) or with
noncompressible arteries (ABI >1.40 and TBI 0.70) in the setting of
IIa B-NR
nonhealing wounds or gangrene, TBI with waveforms, TcPO2, or SPP can
be useful to evaluate local perfusion (112-116).
See Online Data Perfusion assessment measures (e.g., TBI with waveforms, TcPO2, SPP) can be
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2016 AHA/ACC Lower Extremity PAD Guideline
Supplement 5. useful when the ABI is only mildly reduced (e.g., ABI 0.700.90) to determine
whether factors other than PAD may be contributing to impaired wound healing
(Figure 2). These perfusion assessment measures are obtained in a warm room to
prevent arterial vasoconstriction in response to the cold. TcPO2 measurements
are performed with a standardized protocol and are taken at multiple sites(117).
The likelihood of wound healing decreases with toe pressure <30 mm Hg (100).
PT
There is correlation between TBI, TcPO2, and SPP. TcPO2 >30 mm Hg has been
used to predict ulcer healing (118). SPP 30 to 50 mm Hg is associated with
increased likelihood of wound healing (113). TcPO2 and SPP can be used in
angiosome-targeted assessment for revascularization (119). Additional perfusion
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assessment may also be useful for patients with nonhealing wounds or gangrene
who have noncompressible arteries (ABI >1.40) but who have a diagnosis of
PAD that is based on an abnormal TBI (ABI 0.70).
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Table 6. Alternative Diagnoses for Leg Pain or Claudication With Normal Physiological Testing (Not
PAD-Related)
Effect of Effect of Effect of Other
Condition Location Characteristic
Exercise Rest Position Characteristics
Symptomatic Behind Swelling, With exercise Also present None Not intermittent
Bakers cyst knee, down tenderness at rest
calf
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Venous Entire leg, Tight, bursting After walking. Subsides Relief speeded History of
claudication worse in pain slowly by elevation iliofemoral deep
calf vein thrombosis;
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edema; signs of
venous stasis
Chronic Calf Tight, bursting After much Subsides very Relief with Typically heavy
compartment muscles pain exercise slowly rest muscled athletes
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syndrome (jogging)
Spinal Often Pain and May mimic Variable Relief by Worse with
stenosis bilateral weakness claudication relief but can lumbar spine standing and
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buttocks, take a long flexion extending spine
posterior time to
leg recover
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Nerve root Radiates Sharp Induced by Often present Improved by History of back
compression down leg lancinating pain sitting, at rest change in problems; worse
standing, or position with sitting; relief
walking when supine or
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sitting
Hip arthritis Lateral hip, Aching After variable Not quickly Improved Symptoms
thigh discomfort degree of relieved when not variable;
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Foot/ankle Ankle, Aching pain After variable Not quickly May be Symptoms
arthritis foot, arch degree of relieved relieved by not variable; may be
exercise bearing weight related to activity
level or present at
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rest
Modified from Norgren L, et al. (35).
PAD indicates peripheral artery disease.
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Table 7. Alternative Diagnoses for Nonhealing Wounds With Normal Physiological Testing (Not PAD-
Related)
Condition Location Characteristics and Causes
Venous ulcer Distal leg, Develops in regions of skin changes due to chronic venous disease
especially above and local venous hypertension
medial mellolus Typically wet (i.e., wound drainage) rather than dry lesion
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Distal small arterial Toes, foot, leg Diabetic microangiopathy
occlusion End-stage renal disease
(microangiopathy) Thromboangiitis obliterans (Buergers)
Sickle-cell anemia
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Vasculitis (e.g., Churg-Strauss, Henoch-Schonlein purpura,
leukocytoclastic vasculitis, microscopic polyangiitis, polyarteritis
nodosa)
Scleroderma
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Cryoagglutination
Embolic (e.g., cholesterol emboli, thromboemboli, endocarditis)
Thrombotic (e.g., antiphospholipid antibody syndrome, Sneddons
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syndrome, warfarin skin necrosis, disseminated intravascular
coagulation, livedoid vasculitis, protein C or S deficiency,
prolonged vasospasm)
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Local injury Toes, foot, leg Trauma
Insect or animal bite
Burn
Medication related Toes, foot, leg Drug reactions (e.g., erythema multiforme)
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Autoimmune injury Toes, foot, leg With blisters (e.g., pemphigoid, pemphigus, epidermolysis bullosa)
Without blisters (e.g., dermatomyositis, lupus, scleroderma)
Infection Toes, foot, leg Bacterial (e.g., pseudomonas, necrotizing streptococcus)
Fungal (e.g., blastomycosis, Madura foot, chromomycosis)
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Mycobacterial
Parasitic (e.g., Chagas, leishmaniasis)
Viral (e.g., herpes)
Malignancy Toes, foot, leg
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TE
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ABI indicates ankle-brachial index; CLI, critical limb ischemia; CTA, computed tomography angiography; MRA, magnetic
resonance angiography; TcPO2, transcutaneous oxygen pressure; and TBI, toe-brachial index.
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2016 AHA/ACC Lower Extremity PAD Guideline
PT
anatomic location and severity of stenosis for patients with symptomatic
PAD in whom revascularization is considered (118, 120-122).
For symptomatic patients in whom ABI/TBI confirms PAD and in whom
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revascularization is considered, additional imaging with duplex ultrasonography,
CTA, or MRA is useful to develop an individualized treatment plan, including
assistance in selection of vascular access sites, identification of significant
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lesions, and determination of the feasibility of and modality for invasive
treatment. All 3 of these noninvasive imaging methods have good sensitivity and
specificity as compared with invasive angiography (118, 120-122). Renal
function does not affect the safety of duplex ultrasonography, although duplex
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offers lower spatial resolution than CTA and MRA in the setting of arterial
See Online Data calcification. The tomographic data from CTA and MRA afford 3-dimensional
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Supplement 6. reconstruction of the vessels examined. The iodinated contrast used in CTA
confers risk of contrast-induced nephropathy and (rarely) severe allergic reaction
(123, 124); CTA uses ionizing radiation. MRA does not use ionizing radiation;
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By definition, CLI results from extensive PAD that limits tissue perfusion.
Because timely diagnosis and treatment are essential to preserve tissue viability
N/A in CLI, it is often most effective and expeditious to pursue invasive angiography
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for anatomic assessment may be perceived to confer greater risk to the patient
than invasive angiography (e.g., patient with advanced chronic kidney disease for
whom contrast dose for invasive angiography would be lower than that required
for CTA).
Invasive and noninvasive angiography (i.e., CTA, MRA) should not be
III:
B-R performed for the anatomic assessment of patients with asymptomatic PAD
Harm
PT
(123, 124, 126).
Angiography, either noninvasive or invasive, should not be performed for the
anatomic assessment of patients with PAD without leg symptoms because
See Online Data delineation of anatomy will not change treatment for this population. This lack of
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Supplements 6 benefit occurs in the setting of risk of contrast-induced nephropathy, patient
and 7. discomfort, and allergic reactions (123, 124, 126).This recommendation does not
SC
address assessment of lower extremity aneurysmal disease or nonatherosclerotic
causes of arterial disease, which is beyond the scope of this document.
PAD has been recognized as a risk factor for AAA. In observational studies, the
prevalence of AAA (aortic diameter 3 cm) was higher in patients with symptomatic
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PAD than in the general population (127, 129) and in a population of patients with
atherosclerotic risk factors (128). The prevalence of AAA among patients with PAD
increased with age, beginning in patients 55 years of age, and was highest in patients
See Online Data
75 years of age (129). There are no data on AAA screening in patients with
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Supplement 8.
asymptomatic PAD. This recommendation refers to screening patients with
symptomatic PAD for AAA regardless of patient age, sex, smoking history, or family
history of AAA. Recommendations for screening the general population with risk
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factors for AAA (based on age, sex, smoking history, and family history) have been
previously published (9).
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that screening all patients with PAD for asymptomatic atherosclerosis in other arterial beds improves clinical
outcome. Intensive treatment of risk factors through GDMT is the principle method for preventing adverse
cardiovascular ischemic events from asymptomatic disease in other arterial beds.
PT
Patients with PAD should receive a comprehensive program of GDMT, including structured exercise and
lifestyle modification, to reduce cardiovascular ischemic events and improve functional status. Smoking
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cessation is a vital component of care for patients with PAD who continue to smoke. A guideline-based program
of pharmacotherapy to reduce cardiovascular ischemic events and limb-related events should be prescribed for
each patient with PAD and is customized to individual risk factors, such as whether the patient also has diabetes
SC
mellitus. Previous studies have demonstrated that patients with PAD are less likely to receive GDMT than are
patients with other forms of cardiovascular disease, including coronary artery disease (CAD) (136-138).
I A alone (75 mg per day) is recommended to reduce MI, stroke, and vascular death
in patients with symptomatic PAD (139-142).
The effect of antiplatelet therapy on cardiovascular events has been systematically
D
Among patients patients with symptomatic PAD treated with antiplatelet therapy,
there was a 22% odds reduction for cardiovascular events, including MI, stroke, or
vascular death (139). Symptomatic patients with lower extremity PAD included both
those with claudication and those with prior lower extremity revascularization. The
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See Online Data 1500 mg daily, whereas there was a significantly smaller (13%) reduction in
Supplement 13. cardiovascular events in patients being treated with <75 mg of aspirin per day (139).
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PT
increased cardiovascular risk (79). Subgroup analysis in a trial evaluating
See Online Data asymptomatic patients did not show an effect of aspirin in patients with an abnormally
Supplement 13. low ABI (<0.80 or 0.90) (76). However, the trial was not powered to analyze
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subgroups, and the uncertainty of the result does not rule out the possibility that
aspirin could provide benefit in such patients, especially in those at increased risk of
cardiovascular events. Another trial that included asymptomatic patients was too
SC
small to derive meaningful conclusions (140).
In asymptomatic patients with borderline ABI (0.910.99), the usefulness of
IIb B-R antiplatelet therapy to reduce the risk of MI, stroke, or vascular death is
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uncertain (75, 76, 139, 142).
In asymptomatic patients with an abnormal or borderline ABI, 2 RCTs found that
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aspirin had no effect in reducing cardiovascular events (75, 76) and might increase
bleeding (76). However, the trials were not powered to examine patients with
See Online Data
borderline ABI separately. Given that cardiovascular risk is lower in patients with
Supplement 13.
borderline ABI than in those with abnormal ABI (80), it would be unlikely that
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aspirin would have a meaningful effect in this subgroup when there was no evidence
of an effect in the total trial populations.
The effectiveness of dual-antiplatelet therapy (DAPT) (aspirin and clopidogrel)
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IIb B-R to reduce the risk of cardiovascular ischemic events in patients with symptomatic
PAD is not well established (143, 144).
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See Online Data events who are not at high risk of bleeding (143, 144). Currently, there are sparse data
Supplement 13. on newer P2Y12 antagonists for PAD. There is uncertainty about the net benefit of
long-term DAPT for patients with PADspecifically the balance of risks of
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cardiovascular ischemic events versus major bleeding. Additional clinical trials are
needed in the population with PAD. Refer to the DAPT guideline focused update for
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There are sparse data on DAPT after lower extremity revascularization. Still, DAPT is
prescribed in up to 55% of patients after endovascular revascularization for CLI
(146). One small RCT of aspirin or aspirin plus clopidogrel in patients undergoing
endovascular revascularization demonstrated that patients with DAPT had fewer
repeat revascularization procedures for clinical symptoms (145). A subsequent small
See Online Data
RCT of aspirin plus placebo or aspirin plus clopidogrel in patients after endovascular
Supplements 13
PT
revascularization also showed a decrease in the need for repeat revascularization at 6
and 14.
months in patients receiving clopidogrel (147). An RCT of aspirin plus placebo or
aspirin plus clopidogrel in patients who underwent below-knee bypass graft showed a
decrease in limb-related events only in the prespecified subgroup of patients with
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prosthetic bypass grafts (148). Refer to the DAPT guideline focused update for DAPT
recommendations specifically for CAD (20).
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IIb B-R The overall clinical benefit of vorapaxar added to existing antiplatelet therapy in
patients with symptomatic PAD is uncertain (149-152).
This novel antagonist of protease-activated receptor-1 added to existing antiplatelet
therapy reduced the risk of cardiovascular ischemic events in patients with
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atherosclerosis who were receiving standard therapy in an RCT (150, 151). However,
it also increased the risk of moderate or severe bleeding. Although the cardiovascular
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benefit was not demonstrated in the subgroup with symptomatic PAD, there was a
See Online Data
reduction in limb-related events with vorapaxar, specifically in acute limb ischemia
Supplement 13.
(ALI) and peripheral revascularization (149, 152). More than half of ALI events in the
PAD subset were due to thrombosis of lower extremity bypass grafts (149).
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Unfortunately, the benefit in limb events in patients with PAD was accompanied by
an increased risk of bleeding (149, 152). Therefore, the overall clinical benefit of
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I A 153-157).
Statin therapy improves both cardiovascular and limb outcomes in patients with PAD
(157). In a subgroup of 6,748 patients with PAD in the HPS (Heart Protection Study),
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simvastatin 40 mg daily reduced the rate of first major vascular event by 22% relative
to placebo (155).
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PAD, statin treatment improved cardiovascular outcomes (96). Guidelines for dosing
and risks of statin medications have been previously published (24).
PT
Antihypertensive therapy should be administered to patients with hypertension
I A and PAD to reduce the risk of MI, stroke, heart failure, and cardiovascular
death (158-162).
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Treatment of elevated blood pressure is indicated to lower the risk of cardiovascular
events (162). Target blood pressure and selection of antihypertensive therapy should
be consistent with current published guidelines for hypertension management.
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Concerns have been raised that antihypertensive therapy may reduce limb perfusion.
See Online Data
However, multiple studies have demonstrated that blood pressure treatment, including
Supplements 17
the use of beta blockers, does not worsen claudication symptoms or impair functional
and 18.
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status in patients with PAD (163-165). There is no evidence that one class of
antihypertensive medication or strategy is superior for blood pressure lowering in
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PAD (158, 166, 167). An updated multisocietal guideline on the management of high
blood pressure is anticipated in 2017.
The use of angiotensin-converting enzyme inhibitors or angiotensin-receptor
IIa A blockers can be effective to reduce the risk of cardiovascular ischemic events in
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Evaluation) trial (168, 169). Patients were normotensive on average at the time of
enrollment. In a subgroup of 4,051 patients with PAD, ramipril reduced the risk of
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MI, stroke, or vascular death by 25%, similar to the efficacy in the entire study
population (168, 169). The efficacy was similar in patients with PAD with
symptomatic disease and asymptomatic low ABI (168). ONTARGET (Ongoing
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See Online Data Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial)
Supplement 17. compared telmisartan, ramipril, and combination therapy in patients with
cardiovascular disease, including PAD, and/or diabetes mellitus (169). All 3
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treatments had similar cardiovascular event rates with higher rates of adverse events
(including hypotension, syncope, and renal failure) in the combination-therapy group.
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The efficacy of telmisartan was similar in the subgroup of 3,468 patients with PAD,
which supports the use of angiotensin-receptor blockers as an alternative to
angiotensin-converting enzyme inhibitors (161). The effect of angiotensin-receptor
blockers in asymptomatic PAD has not been studied.
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Tobacco use is a strong risk factor for the development and progression of PAD (173,
174). Sparse evidence exists with regard to the association of novel tobacco product
use, including electronic cigarettes, and PAD (175). Observational studies suggest
See Online Data
that smoking cessation is associated with lower rates of cardiovascular ischemic
Supplements 19
events, limb-related events, bypass graft failure, amputation, and death in patients
and 20.
with PAD (172, 176-178). Clinician advice increases quit rates, which supports
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simple provider-based measures as a component of smoking cessation programs (22,
171, 179).
Patients with PAD who smoke cigarettes should be assisted in developing a plan
for quitting that includes pharmacotherapy (i.e., varenicline, bupropion, and/or
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I A
nicotine replacement therapy) and/or referral to a smoking cessation program
(170, 180-182).
Coordinated smoking cessation interventions that include nonpharmacological and
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pharmacological approaches have the greatest efficacy. An RCT of a follow-up
program and smoking cessation medications provided to hospitalized patients,
including those with PAD, demonstrated a modest increase in quit rates (181). In an
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RCT of patients with PAD specifically, a comprehensive smoking cessation program
See Online Data combining counseling and pharmacological agents increased the rates of smoking
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Supplements 19 cessation to 21.3%, compared with 6.8% with standard advice (170). Three
and 20. pharmacological approaches (i.e., varenicline, bupropion, and nicotine replacement
therapy) used alone or in combination all increase smoking cessation rates (179, 180,
182). Two meta-analyses of RCTs of smoking cessation medications showed no
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I B-NR Patients with PAD should avoid exposure to environmental tobacco smoke at
work, at home, and in public places (185, 186).
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Passive smoke exposure has been associated with the development of PAD (186).
See Online Data Observational studies have shown lower cardiovascular and cerebrovascular event
Supplement 20. rates in the general population after enactment of smoke-free legislation (185). The
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effects of avoidance of passive smoke exposure on limb-related events are not known.
I C-EO Management of diabetes mellitus in the patient with PAD should be coordinated
between members of the healthcare team.
Diabetes mellitus is an important risk factor for the development of PAD (187).
Furthermore, the presence of diabetes mellitus increases the risk of adverse outcomes
among patients with PAD, including progression to CLI, amputation, and death (188,
189). A comprehensive care plan for patients with PAD and diabetes mellitus is
N/A
important and may include diet and weight management, pharmacotherapy for
glycemic control and management of other cardiovascular risk factors, and foot care
and ulcer prevention (25, 190). Guidelines for glycemic control among patients with
diabetes mellitus and atherosclerotic vascular disease have been previously published
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(25, 29). Regular follow-up with and communication among the patients healthcare
providers, including vascular specialists and diabetes care providers (e.g., primary
care physicians, endocrinologists) constitute an important component of care for
patients with PAD and diabetes mellitus.
IIa B-NR Glycemic control can be beneficial for patients with CLI to reduce limb-related
outcomes (191, 192).
In a cohort of 1,974 participants with diabetes mellitus from the Strong Heart Study,
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compared with patients without PAD, patients with PAD and a Hg A1c level <6.5%
had lower age-adjusted odds of major amputation compared to patients with PAD and
hemoglobin A1c 6.5% to 9.5% and hemoglobin A1c >9.5% (188). Glycemic control
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See Online Data is particularly important for patients with PAD and diabetes mellitus who have CLI.
Supplement 22. Single-center observational studies have demonstrated improved limb-related
outcomes, including lower rates of major amputation and improved patency after
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infrapopliteal intervention, among patients with CLI who have more optimized
glycemic control parameters compared with patients with inferior glycemic control
(191, 192).
the subgroup of patients with autogenous vein bypass grafts (193, 194). However, a
Cochrane systematic review showed no patency benefit with the use of
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anticoagulation compared with antiplatelet therapy (195). All RCTs and observational
See Online Data studies evaluating the effect of anticoagulants on bypass patency demonstrated
Supplements 23
increased bleeding complications associated with anticoagulant use. One RCT
and 24.
evaluating the effectiveness of oral anticoagulation (warfarin) in addition to aspirin in
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PT
COR LOE Recommendation
I A Cilostazol is an effective therapy to improve symptoms and increase walking
distance in patients with claudication (199, 200).
In a Cochrane review including 15 double-blind RCTs with a total of 3,718
RI
participants, cilostazol was associated with improvement in claudication symptoms
but no changes in cardiovascular deaths or QoL when compared with placebo (199).
See Online Data
SC
In 1 RCT, cilostazol was more effective than pentoxifylline or placebo (200). Side
Supplement 25.
effects include headache, abnormal stool (diarrhea), dizziness, and palpitations.
Cilostazol is contraindicated in patients with congestive heart failure (201). In 1 trial,
20% of patients discontinued cilostazol within 3 months (202).
B-R
Benefit
In a Cochrane review of 24 studies with 3,377 participants, there was large variability
in study design and results between individual studies, and therefore the reviews
D
Supplement 26.
patients with moderate-to-severe claudication, there was no difference between
pentoxifylline and placebo in the primary endpoint of maximal walking distance
(200). Therefore, pentoxifylline is not recommended as treatment for claudication.
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Although patients with PAD have been shown to have increased plasma
homocysteine levels compared with patients without PAD, there is no evidence that
B-complex vitamin supplementation improves clinical outcomes in patients with PAD
See Online Data (207). The HOPE-2 trial randomized 5,522 patients with atherosclerotic vascular
Supplements 28 and
disease, including symptomatic PAD, or diabetes mellitus with additional risk factors
29.
to receive folic acid/vitamin B6/vitamin B12 or placebo (205, 206). Despite lowering
PT
of homocysteine levels in the vitamin supplementation arm, there was no
improvement in the primary endpoint of cardiovascular death, MI, or stroke.
RI
Recommendation for Influenza Vaccination
COR LOE Recommendation
SC
I C-EO Patients with PAD should have an annual influenza vaccination.
Observational studies have demonstrated reduced cardiovascular event rates among
patients with cardiovascular disease who have received an influenza vaccination (30).
U
Two RCTs that enrolled patients with CAD demonstrated a benefit of an influenza
See Online Data vaccination on the prevention of cardiovascular events, particularly coronary ischemic
AN
Supplements 30 and
events (208, 209). Although these trials did not specifically enroll participants with
31.
PAD, a majority of patients with PAD also have CAD (30). On the basis of this
evidence, an annual influenza vaccination is recommended as a component of medical
M
Structured exercise therapy is an important element of care for the patient with PAD. Components of structured
TE
The data supporting the efficacy of supervised exercise training as an initial treatment
for claudication continue to develop and remain convincing, building on many earlier
AC
RCTs (40-46, 48, 210, 211). Trials with long-term follow-up from 18 months (37, 38)
to 7 years (36) have demonstrated a persistent benefit of supervised exercise in
patients with claudication. Data also support a benefit of supervised exercise for
See Online Data patients with symptomatic PAD and diabetes mellitus (212). The riskbenefit ratio for
Supplement 32. supervised exercise in PAD is favorable, with an excellent safety profile in patients
screened for absolute contraindications to exercise such as exercise-limiting
cardiovascular disease, amputation or wheelchair confinement, and other major
comorbidities that would preclude exercise (36, 39, 49, 213-216). Despite the health
benefits associated with supervised exercise in patients with PAD, initiating and
maintaining a high level of adherence remain challenging. Frequent contact with
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patients both when performing exercise in the supervised setting and at home has
been somewhat effective in promoting retention (37, 38).
A supervised exercise program should be discussed as a treatment option for
I B-R
claudication before possible revascularization (36-38).
The CLEVER (Claudication: Exercise Versus Endoluminal Revascularization) trial
randomized patients with symptomatic aortoiliac PAD and showed comparable
benefits for supervised exercise and stent revascularization at 6 and 18 months, with
PT
each therapy being superior to optimal medical care (37, 38). Overall, the safety
profile for supervised exercise was excellent. An RCT that compared 7-year
effectiveness of supervised exercise or endovascular revascularization in patients with
RI
stable claudication with iliac or femoropopliteal disease found no differences in
improved walking and QoL outcomes (36). Although more secondary interventions
occurred in the exercise group, the total number of interventions was greater in the
SC
endovascular revascularization group. Collectively, these studies provide strong
support for offering patients a supervised exercise program for reducing claudication
See Online Data symptoms and for improving functional status and QoL.
Supplement 32.
U
A 3-month RCT that compared percutaneous transluminal angioplasty (PTA),
supervised exercise, and combined treatment for claudication found that both
AN
supervised exercise and PTA improved clinical and QoL outcomes, whereas PTA plus
supervised exercise produced greater benefits than either therapy alone (217). The
ERASE (Endovascular Revascularization and Supervised Exercise) study randomized
participants with claudication to endovascular revascularization plus supervised
M
exercise or supervised exercise alone. After 1 year, patients in both groups had
significant improvements in walking distances and health-related QoL, with greater
D
symptoms atypical for claudication) are more recent than studies supporting
supervised exercise programs, and have provided strong evidence in support of the
AC
community- or home-based approach (47, 49, 51, 88, 94, 213). For example, the
See Online Data GOALS (Group Oriented Arterial Leg Study) trial (94) included patients with
Supplement 32.
confirmed PAD with and without claudication (atypical lower extremity symptoms
or no symptoms) and showed increases in several parameters of functional status for
both of these patient cohort subgroups, versus nonexercising controls, after 6
months (88), with improvement maintained at 12 months (94).
As with supervised exercise programs, despite proven benefit, initiating and
maintaining a high level of adherence to community- or home-based exercise
programs remains challenging. Studies that have incorporated behavioral change
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techniques, such as health coaching and activity tracking used in supervised settings,
appear to reduce attrition and promote higher levels of adherence, thereby improving
functional and QoL outcomes, both short term and long term (49, 88, 94).
In patients with claudication, alternative strategies of exercise therapy, including
upper-body ergometry, cycling, and pain-free or low-intensity walking that
IIa A
avoids moderate-to-maximum claudication while walking, can be beneficial to
improve walking ability and functional status (39, 215, 219, 220).
PT
Protocols for exercise therapy for PAD traditionally have recommended intermittent
walking bouts to moderate or higher pain levels interspersed with short periods of
See Online Data rest. Although these protocols are efficacious, intolerance of pain may lead to poor
RI
Supplements 32 and exercise adherence. An increasing number of studies have shown that modalities of
33. exercise that avoid claudication or walking performed at intensities that are pain free
or produce only mild levels of claudication can achieve health benefits comparable to
SC
walking at moderate or higher levels of claudication pain (39, 41, 215, 219-221).
U
Program takes place in a hospital or outpatient facility.
AN
Program uses intermittent walking exercise as the treatment modality.
Program can be standalone or within a cardiac rehabilitation program.
Program is directly supervised by qualified healthcare provider(s).
Training is performed for a minimum of 3045 min/session; sessions are performed at least 3 times/wk for a
M
minimum of 12 wk (36-46).
Training involves intermittent bouts of walking to moderate-to-maximum claudication, alternating with periods of
rest.
D
Warm-up and cool-down periods precede and follow each session of walking.
Program takes place in the personal setting of the patient rather than in a clinical setting (41, 47-51).
Program is self-directed with guidance of healthcare providers.
Healthcare providers prescribe an exercise regimen similar to that of a supervised program.
Patient counseling ensures understanding of how to begin and maintain the program and how to progress the
EP
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Educational efforts are especially important for patients with PAD who have diabetes
mellitus with peripheral neuropathy.
I C-LD In patients with PAD, prompt diagnosis and treatment of foot infection are
recommended to avoid amputation (224-228).
Foot infections (infection of any of the structures distal to the malleoli) may include
cellulitis, abscess, fasciitis, tenosynovitis, septic joint space infection, and
osteomyelitis. Studies have investigated the accuracy of physical findings for
PT
identification of infection and determining infection severity and risk of amputation
(224-226).
Because of the consequences associated with untreated foot infection
RI
especially in the presence of PADclinicians should maintain a high index of
suspicion (228). It is also recognized that the presence of diabetes mellitus with
See Online Data
peripheral neuropathy and PAD may make the presentation of foot infection more
SC
Supplement 34.
subtle than in patients without these problems. Foot infection should be suspected if
the patient presents with local pain or tenderness; periwound erythema; periwound
edema, induration or fluctuance; pretibial edema; any discharge (especially
U
purulent); foul odor; visible bone or a wound that probes-to-bone; or signs of a
systemic inflammatory response (including temperature >38C or <36C, heart rate
AN
>90/min, respiratory rate >20/min or PaCO2 <32 mm Hg, white blood cell count
>12,000 or <4,000/mcL or >10% immature forms) (226). Probe-to-bone test is
moderately predictive for osteomyelitis but is not pathognomonic (227).
M
IIa C-LD In patients with PAD and signs of foot infection, prompt referral to an
interdisciplinary care team (Table 9) can be beneficial (228-230).
The EuroDIALE (European Study Group on Diabetes and the Lower Extremity)
study demonstrated that the presence of both PAD and foot infection conferred a
D
nearly 3-fold higher risk of leg amputation than either infection or PAD alone (228).
The treatment of deep soft-tissue infection typically requires prompt surgical
TE
IIa C-EO It is reasonable to counsel patients with PAD without diabetes mellitus about
AC
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A history of foot ulcers, foot infections, or amputation identifies patients with a very
high (>10%) yearly incidence of recurrent ulcers (231). Examination includes a
N/A visual inspection for foot ulcers (full-thickness epithelial defects) and structural
(bony) deformities, monofilament testing for sensory neuropathy, and palpation for
pedal pulses.
PT
Table 9. 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
RI
endovascular revascularization, surgical revascularization, wound healing therapies and foot surgery, and medical
evaluation and care.
Interdisciplinary care team members may include:
SC
o Vascular medical and surgical specialists (i.e., vascular medicine, vascular surgery, interventional radiology,
interventional cardiology)
o Nurses
o Orthopedic surgeons and podiatrists
U
o Endocrinologists
o Internal medicine specialists
o Infectious disease specialists
AN
o Radiology and vascular imaging specialists
o Physical medicine and rehabilitation clinicians
o Orthotics and prosthetics specialists
o Social workers
M
o Exercise physiologists
o Physical and occupational therapists
o Nutritionists/dieticians
CLI indicates critical limb ischemia; and PAD, peripheral artery disease.
D
TE
should have a customized care plan that also includes medical therapy (Section 5), structured exercise therapy
(Section 6), and care to minimize tissue loss (Section 7). If a strategy of revascularization for claudication is
C
undertaken, the revascularization strategy should be evidence based and can include endovascular
revascularization, surgery, or both.
AC
Because of the variability of ischemic limb symptoms and impact of these symptoms on functional status
and QoL, patients should be selected for revascularization on the basis of severity of their symptoms. Factors to
consider include a significant disability as assessed by the patient, adequacy of response to medical and
structured exercise therapy, status of comorbid conditions, and a favorable riskbenefit ratio. Patient preferences
and goals of care are important considerations in the evaluation for revascularization. The revascularization
strategy should have a reasonable likelihood of providing durable relief of symptoms. A general
recommendation for revascularization as a treatment option for claudication is provided below followed by
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specific recommendations for endovascular (Section 8.1.1) and surgical (Section 8.1.2) procedures if a
revascularization strategy is undertaken.
PT
COR LOE Recommendation
Revascularization is a reasonable treatment option for the patient with lifestyle-
IIa A limiting claudication with an inadequate response to GDMT (12, 37, 38, 232,
233).
RI
A minority of patients with claudication (estimated at <10% to 15% over 5 years or
more) will progress to CLI (234-237). Therefore, the role of revascularization in
claudication is improvement in claudication symptoms and functional status, and
SC
consequently in QoL, rather than limb salvage. Revascularization is reasonable when
See Online Data the patient who is being treated with GDMT (including structured exercise therapy)
Supplements 35 and presents with persistent lifestyle-limiting claudication (12, 37, 38, 232, 233).
U
36. Lifestyle-limiting claudication is defined by the patient rather than by any test. It
includes impairment of activities of daily living and/or vocational and/or recreational
AN
activities due to claudication. There should be clear discussion with the patient about
expected risks and benefits of revascularization, as well as discussion of the
durability of proposed procedures.
M
These techniques continue to involve and now include covered stents, drug-eluting stents (DES), cutting
balloons, and drug-coated balloons. The technique chosen for endovascular treatment is related to lesion
TE
characteristics (e.g., anatomic location, lesion length, degree of calcification) and operator experience.
Assessment of the appropriateness of specific endovascular techniques for specific lesions for the treatment of
EP
distal limb. Stenoses of 50% to 75% diameter by angiography may not be hemodynamically significant, and
AC
resting or provoked intravascular pressure measurements may be used to determine whether lesions are
significant (238, 239). Multiple RCTs have compared endovascular procedures to various combinations of
medical treatment with or without supervised or unsupervised exercise programs (12, 37, 38, 217, 232, 233,
240-251). These trials have used different endpoints and enrolled patients with anatomic disease distribution at
different levels.
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walking parameters and QoL (11, 12, 233). The CLEVER trial enrolled only patients
with aortoiliac disease and compared endovascular therapy to supervised exercise
therapy and to medications alone (37, 38). At 6-month follow-up, both the
RI
endovascular therapy and supervised exercise groups had improved peak walking
time compared with medication alone, with a greater improvement in the supervised
exercise group (37). By 18 months, there was no significant difference between the
SC
endovascular therapy and supervised exercise groups, with a sustained benefit versus
See Online Data medication alone (38). Other RCTs that included patients with aortoiliac disease have
Supplements 35 shown QoL, as assessed by questionnaires and time to onset of claudication, may be
and 36.
U
superior with endovascular treatment in combination with a medical and an exercise
treatment plan, compared versus medical treatment alone (232, 233, 246). The
AN
ERASE trial randomized patients with claudication and aortoiliac (as well as
femoropopliteal) disease to endovascular revascularization plus supervised exercise or
supervised exercise alone. After 1 year, patients in both groups had significant
improvements in walking distances and health-related QoL, with greater
M
medical therapy, with benefit that diminishes by 1 year (217, 232, 240-246, 250, 251).
Two separate systematic reviews that included RCTs that enrolled patients with
femoropopliteal disease, reported that endovascular treatment of claudication
C
improved walking parameters and QoL (11, 12, 233). The durability of endovascular
See Online Data treatment for claudication is directly related to vessel patency. Long-term patency is
AC
Supplement 35. greater in the iliac artery than in the femoropopliteal segment. Furthermore, durability
is diminished with greater lesion length, occlusion rather than stenosis, the presence
of multiple and diffuse lesions, poor-quality runoff, diabetes mellitus, chronic kidney
disease, renal failure, and smoking (252-255). The choice of endovascular therapy as
a revascularization approach for claudication due to femoropopliteal disease therefore
should include a discussion of outcomes, addressing the risk of restenosis and repeat
intervention, particularly for lesions with poor likelihood of long-term durability.
The usefulness of endovascular procedures as a revascularization option for
IIb C-LD patients with claudication due to isolated infrapopliteal artery disease is
unknown (256-258).
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PT
neither of these studies included patient-oriented outcomes, such as walking function
or QoL parameters. Additional efficacy data on the use of infrapopliteal drug-coated
balloon or DES for the treatment of claudication are likely to be published in the near
future.
RI
III: Endovascular procedures should not be performed in patients with PAD solely to
B-NR
Harm prevent progression to CLI (234-237, 259-261).
There are no data to support a practice paradigm of performing endovascular
SC
procedures on patients with PAD for the purpose of preventing progression of
claudication symptoms to CLI. Reported rates of amputation or progression to CLI
from prospective cohort studies of patients with claudication are <10% to 15% over 5
U
See Online Data years or more, and increased mortality rate associated with claudication is usually the
Supplements 36 and result of cardiovascular events rather than limb-related events (234-237, 262).
AN
38. Similarly, there are no data to support revascularization in patients with asymptomatic
PAD. Procedural risks include bleeding, renal failure from contrast-induced
nephropathy, and the possibility of adverse limb outcomes (259-261). Therefore, the
known risks of endovascular procedures outweigh any hypothetical benefit of
M
The superficial femoral and proximal popliteal arteries are the most common
anatomic sites of stenosis or occlusion among individuals with claudication.
Femoral-popliteal bypass is therefore one of the most common surgical procedures
C
for claudication and may be performed under general or regional anesthesia. The
type of conduit and site of popliteal artery anastomosis (above versus below knee)
AC
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PT
patency outcomes for surgical interventions may be superior versus less invasive
endovascular treatments for specific patients, surgical interventions are also
associated with greater risk of adverse perioperative events (280-286). Treatment
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See Online Data selection should therefore be individualized on the basis of the patients goals,
Supplements 37
perioperative risk, and anticipated benefit. Surgical procedures for claudication are
and 38.
usually reserved for individuals who a) do not derive adequate benefit from
SC
nonsurgical therapy, b) have arterial anatomy favorable to obtaining a durable result
with surgery, and c) have acceptable risk of perioperative adverse events. Acceptable
risk is defined by the individual patient and provider on the basis of symptom
U
severity, comorbid conditions, and appropriate GDMT risk evaluation. Guidelines
for the evaluation and management of patients undergoing noncardiac surgery,
AN
including vascular surgical procedures, have been previously published (21).
III: Femoral-tibial artery bypasses with prosthetic graft material should not be used
B-R
Harm for the treatment of claudication (287-289).
Bypasses to the tibial arteries with prosthetic material for treatment of claudication
M
See Online Data should be avoided because of very high rates of graft failure and amputation (287-
Supplement 37.
289).
III: Surgical procedures should not be performed in patients with PAD solely to
D
B-NR
Harm prevent progression to CLI (234-237, 262).
Claudication does not commonly progress to CLI. Reported rates of amputation or
TE
progression to CLI from prospective cohort studies of patients with claudication are
<10% to 15% for 5 years or more, and increased mortality rate associated with
See Online Data claudication is usually the result of cardiovascular events rather than limb-related
Supplements 37
events (234-237, 262). Surgical intervention should not be performed primarily to
EP
and 38.
prevent disease progression, given the risk of adverse perioperative events without
potential for significant benefit. Similarly, there are no data to support surgical
revascularization in patients with asymptomatic PAD to prevent progression to CLI.
C
AC
9. Management of CLI
Patients with CLI are at increased risk of amputation and major cardiovascular ischemic events. Care of the
patient with CLI includes evaluation for revascularization and wound healing therapies, with the objective to
minimize tissue loss, completely heal wounds, and preserve a functional foot. Medical therapy to prevent
cardiovascular ischemic events is also an important component of care for the patient with CLI (Section 5).
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rate and a 22% rate of major amputation at a median follow-up of 12 months (290).
See Online Data
The goal of surgical or endovascular revascularization is to provide in-line blood flow
Supplement 39.
to the foot through at least 1 patent artery, which will help decrease ischemic pain and
RI
allow healing of any wounds, while preserving a functional limb. Multiple RCTs
comparing contemporary surgical and endovascular treatment for patients with CLI
are ongoing (16, 17, 291). Revascularization is not warranted in the setting of a
SC
nonviable limb.
An evaluation for revascularization options should be performed by an
I C-EO
interdisciplinary care team (Table 9) before amputation in the patient with CLI.
U
Patients with CLI should be evaluated by an interdisciplinary care team. Before
amputation, evaluation generally includes imaging for assessment of revascularization
N/A options (e.g., duplex ultrasound, CTA, MRA, or catheter-based angiogram). The
AN
objective of this strategy is to minimize tissue loss and preserve a functional limb with
revascularization.
M
I B-R Endovascular procedures are recommended to establish in-line blood flow to the
foot in patients with nonhealing wounds or gangrene (292, 293).
TE
Supplement 39.
is an effective option for patients with CLI as compared with open surgery (292, 293).
The primary endpoint of amputation-free survival was the same in the endovascular
AC
and surgical arms. Of note, the endovascular arm used only PTA (292, 293). Multiple
RCTs comparing contemporary surgical and endovascular treatment for patients with
CLI are ongoing (16, 17, 291). Table 10 addresses factors that may prompt an
endovascular versus surgical approach to the patient with CLI.
IIa C-LD A staged approach to endovascular procedures is reasonable in patients with
ischemic rest pain (295, 296).
For patients with multilevel disease who suffer from ischemic rest pain, in-flow
lesions are generally addressed first (295, 296). Depending on procedural
N/A
characteristics, including contrast volume used, radiation exposure, and procedure
time, out-flow lesions can be addressed in the same setting or at a later time if
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symptoms persist. This strategy for ischemic rest pain is distinct from the strategy
recommended for CLI in the patient with a nonhealing wound or gangrene. In that
scenario, restoration of direct in-line flow to the foot is essential for wound healing.
IIa B-R Evaluation of lesion characteristics can be useful in selecting the endovascular
approach for CLI (297, 298).
The lesion characteristics to consider include length, anatomic location, and extent of
occlusive disease. For example, if an adequate angioplasty result can be achieved with
PT
PTA alone for short (<10 cm) stenoses in the femoropopliteal segment, then stent
placement is not necessary (297, 298). Presence of thrombosis or calcification at the
lesion site will also affect the endovascular approach. In general, the advantages of
RI
DES and drug-coated balloons over PTA alone or bare-metal stents are more
See Online Data
consistent in the femoropopliteal segment than for infrapopliteal interventions (257,
Supplement 39.
258, 299-309). However, these differences are mainly for patency, restenosis, and
SC
repeat-revascularization endpoints. Most studies were underpowered or did not
examine other patient-oriented outcomes, such as amputation or wound healing in
CLI. Endovascular techniques continue to evolve rapidly, and there has been limited
U
literature comparing techniques with regard to clinically significant outcomes, such as
amputation or wound healing.
AN
IIb B-NR Use of angiosome-directed endovascular therapy may be reasonable for patients
with CLI and nonhealing wounds or gangrene (310-319).
During the past decade, the goal of care with regard to endovascular therapy for the
treatment of nonhealing wounds due to CLI has been establishment of direct in-line
M
blood flow to the affected limb. The angiosome concept has also been described in the
literature in relation to the treatment of nonhealing wounds. Angiosome-directed
treatment entails establishing direct blood flow to the infrapopliteal artery directly
D
responsible for perfusing the region of the leg or foot with the nonhealing wound.
Multiple retrospective studies and 1 small nonrandomized prospective study assessing
TE
the efficacy of this concept have been published (119, 310-321). Meta-analyses of
these studies found improved wound healing and limb salvage with angiosome-guided
See Online Data
therapy but cautioned that the quality of the evidence was low (322, 323). Although
Supplements 39
EP
angiosome-guided therapy include the potential for longer procedural times, more
contrast exposure, and more technically complex procedures. The impact of all these
factors needs to be weighed against the likelihood of a technically successful
procedure providing hypothetical added benefit over the establishment of in-line
blood flow.
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Table 10. Therapy for CLI: Findings That Prompt Consideration of Surgical or Endovascular
Revascularization
Findings That Favor Consideration of Surgical
Examples
Revascularization
Factors associated with technical failure or poor Lesion involving common femoral artery, including origin of deep
durability with endovascular treatment femoral artery
PT
Long segment lesion involving the below-knee popliteal and/or
infrapopliteal arteries in a patient with suitable single-segment
autogenous vein conduit
RI
Diffuse multilevel disease that would require endovascular
revascularization at multiple anatomic levels
Small-diameter target artery proximal to site of stenosis or densely
SC
calcified lesion at location of endovascular treatment
Endovascular treatment likely to preclude or Single-vessel runoff distal to ankle
complicate subsequent achievement of in-line blood
flow through surgical revascularization
U
Findings That Favor Consideration of
Examples
AN
Endovascular Revascularization
The presence of patient comorbidities may place Patient comorbidities, including coronary ischemia,
patients at increased risk of perioperative cardiomyopathy, congestive heart failure, severe lung disease, and
complications from surgical revascularization. In chronic kidney disease
M
may undergo a staged approach as part of addressed in a staged manner, when required, if clinical factors or
endovascular-first approach patient safety prevent addressing all diseased segments at one
TE
setting
Patients without suitable autologous vein for bypass Some patients have had veins harvested for previous coronary
grafts artery bypass surgery and do not have adequate remaining veins
for use as conduits. Similarly, patients may not have undergone
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PT
In patients with CLI for whom endovascular revascularization has failed and a
IIa B-NR suitable autogenous vein is not available, prosthetic material can be effective for
bypass to the below-knee popliteal and tibial arteries (331-333).
RI
There are studies demonstrating that patients for whom endovascular treatment for
CLI has failed can be treated successfully with autogenous vein bypass graft (332,
See Online Data 333) or prosthetic material (331). Although autogenous vein is the preferred conduit
Supplement 42.
SC
for surgical revascularization, prosthetic conduit is a secondary option for patients
with CLI without suitable saphenous vein who require surgical revascularization.
A staged approach to surgical procedures is reasonable in patients with ischemic
IIa C-LD
rest pain (334-336).
U
It is reasonable to perform a staged approach to revascularization in patients with
ischemic rest pain with multilevel disease. For example, aortoiliac (inflow) disease
AN
may be treated first with endovascular treatment or by surgical reconstruction,
N/A
depending on lesion characteristics, patient comorbidities, and patient preference
(337, 338). Combined percutaneous and surgical revascularization may require
M
separate interventions, typically with the most proximal procedure performed first.
The management of patients with CLI and nonhealing wounds should include
coordinated efforts for both revascularization and wound healing, because the risk of
limb-threatening infections remains until complete wound healing is achieved. The
structure and activities of interdisciplinary care teams for CLI may vary according to
C
several factors, including the local availability of resources. Previous groups have
described various combinations of activities of this team, which are in addition to
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achieved (339).
Revascularization should be coordinated with the efforts of clinicians who
manage foot infections, provide offloading, and achieve complete wound healing,
either through medical therapy, surgical options, or a combination thereof. Coordinated
and timely interdisciplinary care can achieve excellent limb outcomes for patients with
PAD and nonhealing foot wounds (229, 339-341).
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I C-LD In patients with CLI, wound care after revascularization should be performed
with the goal of complete wound healing (339).
A comprehensive plan for treatment of CLI must include a plan for achieving an intact
skin surface on a functional foot. One study demonstrated a limb salvage rate of 100%
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at 3 years in a cohort of patients with CLI who achieved complete wound healing with
endovascular revascularization and dedicated wound care (339). Before
revascularization, the interdisciplinary care team should devise a plan to achieve the
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goal of complete wound healing. After successful revascularization, most patients with
gangrene of the foot are evaluated for minor amputation with staged/delayed primary
closure or surgical reconstruction when feasible (342-344). Negative-pressure wound
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therapy dressings are helpful to achieve wound healing after revascularization and
See Online Data
minor (i.e., digit or partial foot) amputation when primary or delayed secondary
Supplement 44.
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closure is not feasible (345, 346). Spontaneous amputation, or autoamputation, of
gangrenous digits should be reserved for palliation in patients without options for
revascularization (345, 347, 348).
Other evidence-based guidelines relevant to those with nonhealing foot
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wounds following revascularization cover the full spectrum of diabetic foot problems
(349) or separately consider the management of infection (225, 350), offloading (351),
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and wound care (352). To date, there are no trials or high-quality studies that have
focused on wound healing adjuncts in limbs with severe PAD (e.g., topical cytokine
ointments, skin substitutes, cell-based therapies intended to optimize wound healing).
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(353). The potential benefit appears to outweigh the low risk associated with the use of
these devices.
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IIb C-LD In patients with CLI, the effectiveness of hyperbaric oxygen therapy for wound
healing is unknown (354).
The literature evaluating the utility of hyperbaric oxygen therapy has focused on
patients without severe PAD and has not demonstrated a long-term benefit on wound
healing or improving amputation-free survival when compared with sham treatment
See Online Data (355). There are no published studies evaluating the role of hyperbaric oxygen therapy
Supplement 44. for patients with nonreconstructible PAD. One small RCT that focused on patients
with foot ulcers and PAD (ABI <0.80 or TBI <0.70) for whom no revascularization
was planned demonstrated a significant decrease in ulcer area at 6 weeks, but no
significant differences in ulcer size at 6 months, complete ulcer healing at 6 weeks or 6
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 46
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Gerhard-Herman MD, et al.
2016 AHA/ACC Lower Extremity PAD Guideline
months, and major or minor amputations (354). Further research on the utility of
hyperbaric oxygen therapy in this context is needed.
III: No Prostanoids are not indicated in patients with CLI (356).
B-R
Benefit
A systematic review and meta-analysis concluded that RCTs have not demonstrated
See Online Data
meaningful long-term clinical benefit from the administration of prostanoids to patients
Supplement 43.
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with CLI attributable to nonreconstructible PAD (356).
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ALI is one of the most treatable and potentially devastating presentations of PAD. Timely recognition of arterial
occlusion as the cause of an ischemic, cold, painful leg is crucial to successful treatment. The writing committee
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has used a standard definition of ALI in which symptom duration is <2 weeks (Table 3) (33, 34). Category I
refers to viable limbs that are not immediately threatened. Category II refers to threatened limbs. Category IIa
limbs are marginally threatened and salvageable, if promptly treated. Category IIb are immediately threatened
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limbs that require immediate revascularization if salvage is to be accomplished. Category III are irreversibly
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damaged limbs, in which case resultant major tissue loss or permanent nerve damage is inevitable (34).
I C-EO
experience to assess limb viability and implement appropriate therapy.
Patients with ALI should be rapidly evaluated by a vascular specialist if one is
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In patients with suspected ALI, initial clinical evaluation should rapidly assess
I C-LD
limb viability and potential for salvage and does not require imaging (357-361).
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ALI is a medical emergency and must be recognized rapidly. The time constraint is
due to the period that skeletal muscle will tolerate ischemiaroughly 4 to 6 hours
(362). A rapid assessment of limb viability and ability to restore arterial blood flow
See Online Data should be performed by a clinician able to either complete the revascularization or
Supplements 45 triage the patient (358). Lower extremity symptoms in ALI can include both pain and
and 46. loss of function. The longer these symptoms are present, the less likely the possibility
of limb salvage (360, 361). Clinical assessment must include symptom duration, pain
intensity, and motor and sensory deficit severity to distinguish a threatened from a
nonviable extremity (Figure 3). The bedside assessment should include arterial and
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 47
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2016 AHA/ACC Lower Extremity PAD Guideline
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mortality rates associated with ALI are high (360, 363).
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Diagnosis and Management
of ALI
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Acutely cold, painful leg
Suspected ALI
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motor and sensory assessment, arterial
and venous Doppler signals
(Class I)
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Audible arterial Inaudible arterial Inaudible arterial
Audible venous Audible venous Inaudible venous
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Intact Impaired
Sensory loss limited to toes if present Sensory loss more than toes and with rest pain
No muscle weakness Mild or moderate muscle weakness
Salvageable if Salvageable if
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2016 AHA/ACC Lower Extremity PAD Guideline
PT
(35, 364). This can stop thrombus propagation and may provide an anti-inflammatory
effect that lessens the ischemia. Patients who have received heparin before the onset
N/A of ALI and have a decrease in platelet count may have heparin-induced
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thrombocytopenia (365, 366). In this situation, a direct thrombin inhibitor is given,
rather than heparin, if heparin-induced thrombocytopenia with thrombosis is
suspected.
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10.3. Revascularization for ALI: Recommendations
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Recommendations for Revascularization for ALI
COR LOE Recommendations
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In patients with ALI, the revascularization strategy should be determined by
I C-LD local resources and patient factors (e.g., etiology and degree of ischemia) (367-
369).
For marginally or immediately threatened limbs (Category IIa and IIb ALI [Figure
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See Online Data revascularization strategy. The technique that will provide the most rapid restoration
Supplement 47.
of arterial flow with the least risk to the patient should be selected. For example,
catheter-directed thrombolysis can provide rapid restoration of arterial flow to a
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limb (367-371).
Assessment of the comparative effectiveness of catheter-based thrombolysis versus
open surgery is complicated by variable definitions of ALI in this literature. Four
RCTs comparing catheter-based thrombolysis to surgery (367, 369-371), as well as a
meta-analysis (368), have demonstrated similar limb salvage rates between the 2
See Online Data approaches but better survival with catheter-based therapy. The survival advantage of
Supplement 47.
catheter-based therapy may be at least in part attributable to multiple comorbidities
found among the population of patients who present with ALI. Increased
comorbidities are likely to contribute to increased perioperative risk. Several of the
RCTs included patients with relatively chronic ischemia. Acuity and severity are both
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 49
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2016 AHA/ACC Lower Extremity PAD Guideline
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See Online Data immobile because of prolonged ischemia. Patients who have an insensate and
Supplement 48. immobile limb in the setting of prolonged ischemia (>6 to 8 hours) are unlikely to
have potential for limb salvage (34, 362). In addition, in this setting the reperfusion
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and circulation of ischemic metabolites can result in multiorgan failure and
cardiovascular collapse. However, if pain can be controlled and there is no evidence
of infection, amputation may be deferred if this meets with the patients goals.
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Patients with ALI should be monitored and treated (e.g., fasciotomy) for
I C-LD
compartment syndrome after revascularization (372, 373).
The lower extremity muscles reside in compartments, surrounded by fascia and bones.
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Reperfusion to ischemic muscles can cause cellular edema, resulting in increased
compartment pressure. When compartment pressure is >30 mm Hg, there is capillary
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and venule compression that leads to malperfusion of the muscle; this is compartment
See Online Data syndrome. Fasciotomy is indicated when the compartment pressure increases.
Supplement 48.
Measurement of intracompartment pressure is not always easily accessible. In such
cases, evaluation for fasciotomy is prompted by development of increased pain, tense
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muscle, or nerve injury. Fasciotomy should be considered for patients with Category
IIb ischemia for whom the time to revascularization is >4 hours.
In patients with ALI with a salvageable limb, percutaneous mechanical
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IIa B-NR
thrombectomy can be useful as adjunctive therapy to thrombolysis (374-378).
See Online Data Multiple nonrandomized studies have suggested that percutaneous mechanical
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and 50. fibrinolytics. In the event that thromboembolectomy does not restore arterial flow,
bypass can be performed (381-383).
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2016 AHA/ACC Lower Extremity PAD Guideline
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uncovering clinical evidence of other conditions that can result in ALI through either
embolic or thrombotic mechanisms. These conditions include atrial fibrillation, left
ventricular thrombus, aortic dissection, trauma, hypercoagulable state, and presence of a
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limb artery bypass graft. The clinical history should identify the presence or absence of
N/A
a history of MI, symptoms and signs of left ventricular dysfunction resulting in
congestive heart failure, or possible endocarditis. The history should evaluate for
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possibility of deep vein thrombosis with intracardiac shunt (e.g., patent foramen ovale
or other that may result in paradoxical arterial embolism), hypercoagulable state, and
family history of thrombosis.
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IIa C-EO In the patient with a history of ALI, testing for a cardiovascular cause of
thromboembolism can be useful.
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Treatment of ALI should not be delayed for testing for the underlying cause of the limb
ischemia. Delay from symptom onset to revascularization is a major determinant of
outcome (360, 361). The evaluation of a cardiovascular cause of ALI is most useful in
the patient without underlying PAD. Evaluation for cardiovascular cause includes
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N/A
electrocardiogram or additional heart rhythm monitoring to detect atrial fibrillation,
electrocardiogram to detect evidence of MI, and echocardiography to further determine
whether there is a cardiac etiology for thromboembolism, such as valvular vegetation,
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medical therapy, optimizing functional status with structured exercise and, when indicated, revascularization.
functional status.
A comprehensive care plan for patients with PAD includes periodic clinical
evaluation by a healthcare provider with experience in the care of vascular patients.
Clinical evaluation should include assessment of cardiovascular risk factors,
assessment of adherence to medical therapy, and re-evaluation of smoking cessation
N/A efforts. Comprehensive lifestyle modification, including heart-healthy nutrition, is
encouraged (22). Patients with PAD should also undergo periodic assessment of limb
symptoms, functional status, and their ability to participate in vocational and
recreational activities. Ongoing participation in a structured exercise program should
be facilitated. Foot examination and patient counseling about healthy foot behaviors
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 51
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2016 AHA/ACC Lower Extremity PAD Guideline
PT
endovascular) require additional ongoing assessment and care. Follow-up visits after
N/A
revascularization should include reassessment of the patients limb symptoms and
interval change in functional status, as well as participation in a structured exercise
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program. Pulse examination and ABI are included in the assessment. A change in ABI
of 0.15 is considered clinically significant (388).
Duplex ultrasound can be beneficial for routine surveillance of infrainguinal,
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IIa B-R autogenous vein bypass grafts in patients with PAD (389-395).
A general surveillance schedule may be at 4 to 6 weeks, 6 months, and 12 months in
the first year and yearly thereafter. It is important that testing frequency is
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individualized to the patient, type of arterial bypass, and any prior duplex scan
findings. Duplex graft surveillance focuses on the identification of high-grade stenosis
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(e.g., peak systolic velocity >300 cm/s and peak systolic velocity ratio across the
See Online Data stenosis >3.5) or impending graft failure (e.g., PSV <40 cm/s) (392, 395). Detection
Supplements 51 of a graft stenosis prompts the consideration of further revascularization to treat the
and 52. stenosis and maintain graft patency. Duplex may detect significant stenoses that may
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not be detected by a decline in ABI (394). Although case series have demonstrated
high rates of primary assisted patency with a duplex ultrasound-surveillance strategy,
RCTs of duplex surveillance versus clinical surveillance with the ABI have
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demonstrated mixed results in terms of a benefit on patency and limb outcomes (391,
393, 396).
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Supplement 52.
routine duplex surveillance versus clinical surveillance plus the ABI after
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2016 AHA/ACC Lower Extremity PAD Guideline
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Basic science and translational studies to better understand the vascular biology of endovascular
therapies and bypass grafting and to develop new methods for preventing restenosis after
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revascularization.
Determination of risk factors for progression from asymptomatic PAD to symptomatic disease,
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including CLI.
RCTs needed to determine the value of using the ABI to identify asymptomatic patients with PAD
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for therapies to reduce cardiovascular risk (e.g., antiplatelet agents, statins, and other therapies).
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Advancement in PAD diagnostics, such as technologies for simplified yet highly accurate
measurement of the ABI and tools for more reliable noninvasive perfusion assessment in CLI.
Comparative-effectiveness studies to determine the optimal antiplatelet therapy (drug or drugs and
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dosage) for prevention of cardiovascular and limb-related events in patients with PAD.
Development of additional medical therapies for claudicationan area of unmet medical need with
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Studies to investigate the role of dietary intervention, in addition to statin therapy, to improve
outcome and modify the natural history of PAD.
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Additional research to identify the best community- or home-based exercise programs for patients
with PAD to maximize functional status and improve QoL, as well as the role of such exercise
programs before or in addition to revascularization.
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Development and validation of improved clinical classification systems for PAD that incorporate
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symptoms, anatomic factors, and patient-specific risk factors and can be used to predict clinical
outcome and optimize treatment approach. An example of a recently developed classification
system is the Society for Vascular Surgery limb classification system, based on wound, ischemia,
and foot infection (WIfI), which has been validated in different populations and may permit more
meaningful prognosis in patients with CLI (405-409).
Comparative- and cost-effectiveness studies of the different endovascular technologies for treatment
of claudication and CLI, including drug-coated balloons and DES. Studies should include patient-
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 53
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2016 AHA/ACC Lower Extremity PAD Guideline
centered endpoints, such as functional parameters, time to wound healing, and QoL, in addition to
standard patency-focused outcomes. These studies could then be incorporated into value-based
clinical algorithms for approach to revascularization for claudication and CLI.
Additional studies to demonstrate the impact of multisocietal registries on clinical outcomes and
appropriate use. At present, these include the Vascular Quality Initiative (VQI), the National
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Cardiovascular Data Registry Peripheral Vascular Intervention Registry (PVI Registry), and
the National Radiology Data Registry for Interventional Radiology (NRDR). These registries
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provide an opportunity to obtain real-world data on surgical and endovascular procedures for
PAD and to improve quality by providing feedback to participating centers. Future efforts should
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incorporate these registries into interventional RCTs and postmarketing studies of PAD-related
devices.
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13. Advocacy Priorities
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The writing committee identified 3 priorities for multisocietal advocacy initiatives to improve health care for
patients with PAD. First, the writing committee supports the availability of the ABI as the initial diagnostic test
to establish the diagnosis of PAD in patients with history or physical examination findings suggestive of PAD
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(Table 5). Although the ABI test is generally reimbursed by third-party payers for patients with classic
claudication or lower extremity wounds, payers may not provide reimbursement for the ABI with other findings
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suggestive of PAD, such as lower extremity pulse abnormalities or femoral bruits. The writing committee
affirms the importance of confirming the diagnosis of PAD in such patients to allow for GDMT as delineated in
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this document. Second, the writing committee supports the vital importance of insuring access to supervised
exercise programs for patients with PAD. Although extensive high-quality evidence supports supervised
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exercise programs to improve functional status and QoL, only a minority of patients with PAD participate in
such programs because of lack of reimbursement by third-party payers. Third, the writing committee recognizes
the need for incorporation of patient-centered outcomes into the process of regulatory approval of new medical
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therapies and revascularization technologies. For revascularization technologies, regulatory approval is driven
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primarily by data on angiographic efficacy (i.e., target lesion patency) and safety endpoints. The nature of the
functional limitation associated with PAD warrants the incorporation of patient-centered outcomes, such as
functional parameters and QoL, into the efficacy outcomes for the approval process.
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Gerhard-Herman MD, et al.
2016 AHA/ACC Lower Extremity PAD Guideline
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American College of Cardiology/American Heart Association
Lisa Bradfield, CAE, Director, Guideline Methodology and Policy
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Abdul R. Abdullah, MD, Associate Science and Medicine Advisor
Allison Rabinowitz, MPH, Project Manager, Clinical Practice Guidelines
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American Heart Association
Steven R. Houser, PhD, FAHA, President
Nancy Brown, Chief Executive Officer
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Rose Marie Robertson, MD, FAHA, Chief Science and Medicine Officer
Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations
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Comilla Sasson, MD, PhD, FACEP, Vice President, Science and Medicine
Katherine Sheehan, Science and Medicine Advisor, Director of Guidelines Operations
Jody Hundley, Production Manager, Scientific Publications, Office of Science Operations
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Key Words: ACC/AHA Clinical Practice Guideline, peripheral artery disease, claudication, critical limb
ischemia, acute limb ischemia, antiplatelet agents, supervised exercise, endovascular procedures, bypass
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Appendix 1. Author Relationships With Industry and Other Entities (Relevant)2016 AHA/ACC Guideline on the Management of Patients With
Lower Extremity Peripheral Artery Disease (March 2015)
Committee Employment Consultant Speakers Ownership/ Personal Institutional, Expert Voting
Member Bureau Partnership/ Research Organizational, Witness Recusals by
Principal or Other Section*
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Financial Benefit
Marie D. Harvard Medical School None None None None None None None
Gerhard-Herman Associate Professor
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(Chair)
Heather L. Cleveland Clinic Foundation, None None Summit AstraZeneca None None 3.1, 3.2,
Theravasc
SC
Gornik (Vice Cardiovascular Medicine Doppler 5.15.3, and
Chair) Medical Director, Systems 5.6.
Noninvasive Vascular Zin Medical
Laboratory
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Coletta Barrett Our Lady of the Lake None None None None None None None
Regional Medical Center
AN
Vice President
Neal R. Barshes Baylor College of Medicine, None None None None None None None
Division of Vascular Surgery
M
and Endovascular Therapy
Michael E. DeBakey
Department of Surgery
D
Assistant Professor
Matthew A. University of Michigan None None None None None None None
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Corriere Frankel Professor of
Cardiovascular Surgery,
Associate Professor of
EP
Surgery
Douglas E. Massachusetts General Abbott Vascular None None Atrium None None 4, 8.1.1
Drachman HospitalTraining Director St. Jude Medical Medical 9.1.2, and
Bard
C
10.2.2.
Lutonix
AC
Lee A. Fleisher University of Pennsylvania None None None None None None None
Health System Department of
Anesthesiology and Critical
CareChair
Francis Gerry R. University of Edinburgh AstraZeneca None None None None None 5.15.3, 5.6,
Fowkes Emeritus Professor of Bayer 5.10, 7, and
Epidemiology Merck 9.2.
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PT
Hamburg Medicine, Cardiovascular
Medicine SectionAssociate
Professor of Medicine
RI
Scott Kinlay VA Boston Healthcare None None None Medtronic None None 4, 5.6, 8.1.1,
SystemAssociate Chief, The Medicines 9.1.1,
Cardiology Director, Cardiac Company 10.2.1, and
SC
Catheterization Laboratory & 10.2.2.
Vascular Medicine
Robert Lookstein Mount Sinai Medical Boston Scientific Cordis None Shockwave None None 4, 5.6, 8.1.1,
U
Center Chief, Medrad (DSMB) 9.1.1,
Interventional Radiology; Interventional 10.2.1, and
AN
Professor of Radiology and Possis 10.2.2.
Surgery; Vice Chair, The Medicines
Department of Radiology Company
M
Sanjay Misra Mayo Clinic, Division of None None None Johnson & None None 4, 7, 8, and
Vascular and Interventional Johnson 10.2.2.
RadiologyProfessor; (DSMB)
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Department of Radiology
Interventional Radiologist
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Leila Mureebe Duke University Medical None None None None None None None
CenterAssociate Professor
of Surgery, Division of
EP
Vascular Surgery
Jeffrey W. Olin Ichan School of Medicine at AstraZeneca None Northwind AstraZeneca None None 5.15.3, 5.6,
Mount Sinai, Zena and Merck 5.10, and 12.
C
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Queensland School of
MedicineSenior Lecturer
Judith G. University of Colorado, None None None None None None None
RI
Regensteiner Health Sciences Center,
Division of Cardiology
Associate Professor of
SC
Medicine
Andres Schanzer University of Massachusetts Cook Medical None None None None None 4, 8.1.1,
Medical SchoolProfessor 9.1.1, and
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of Surgery and Quantitative 10.2.2.
Health Sciences; Program
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Director, Vascular Surgery
Residency
Mehdi H. Cleveland Clinic, Boston None None None Atrium Medical None 4, 8.1.1
M
Shishehbor Interventional Cardiology and Scientific AstraZeneca 9.1.2, and
Vascular Medicine Medtronic 10.2.2.
Director, Endovascular
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Services
Kerry J. Stewart Johns Hopkins University, None None None None None None None
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School of Medicine; Johns
Hopkins Bayview Medical
CenterProfessor of
EP
Medicine; Director, Clinical
and Research Exercise
Physiology
Diane Treat- University of Minnesota, None None None None None None None
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M. Eileen Walsh University of Toledo, College None None None None None None None
of NursingProfessor
This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document. These relationships were
reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process. The table does not
necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of
5% of the voting stock or share of the business entity, or ownership of $5,000 of the fair market value of the business entity; or if funds received by the person from the
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 58
ACCEPTED MANUSCRIPT
business entity exceed 5% of the persons gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency.
Relationships in this table are modest unless otherwise noted.
According to the ACC/AHA, a person has a relevant relationship IF: a) the relationship or interest relates to the same or similar subject matter, intellectual property or asset,
topic, or issue addressed in the document; or b) the company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes
PT
a competing drug or device addressed in the document; or c) the person or a member of the persons household, has a reasonable potential for financial, professional, or other
personal gain or loss as a result of the issues/content addressed in the document.
*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply.
RI
Significant relationship.
No financial benefit.
SC
ACC indicates American College of Cardiology; AHA, American Heart Association; DSMB, data safety monitoring board; and VA, Veterans Affairs.
U
AN
M
D
TE
C EP
AC
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Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive)2016 AHA/ACC Guideline on the Management of Patients
With Lower Extremity Peripheral Artery Disease (March 2016)
Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
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Benefit
Deepak L. Official Brigham and Womens Elsevier None None Amarin* Belvoir None
Bhatt ReviewerACC HospitalExecutive Amgen* Publications
RI
Board of Director of AstraZeneca* (Editor)*
Trustees Interventional Bristol-Myers Biotronik
Cardiovascular Boston Scientific
SC
Squibb*
Programs; Harvard Cardax Clinical
Medical School Eisai* Cardiology
Professor of Medicine
(Deputy Editor)
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Ethicon*
FlowCo Harvard Clinical
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Forest Research
Laboratories* Institute
Ischemix* HMP
Communications
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Mayo Clinic
Medtronic* (Editor)*
Merck Duke Clinical
Research
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Pfizer*
Institute*
PLx Pharma
Journal of
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Regado
Invasive
Biosciences
Cardiology
Roche* (Editor)*
EP
Sanofi-aventis*
Medscape
St. Jude Medical Cardiology
Takeda Slack
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Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
Mark A. Official Dartmouth-Hitchcock None None None None AHA (Past None
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Creager ReviewerAHA Medical Center President)
Director
Philip Official Dartmouth- None None None NIH* NIH None
RI
Goodney ReviewerAHA HitchcockAssociate
Professor of Surgery
and The Dartmouth
SC
Institute Director
John S. Official Medical University of None None None None None None
Ikonomidis Reviewer South CarolinaChief
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ACC/AHA Task
Force on Clinical
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Practice
Guidelines
Amy W. Official Mayo Clinic None None None None None None
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Pollak ReviewerAHA Cardiovascular
Medicine Physician
Michael D. Official Catholic Health Anthera None None AstraZeneca None None
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White ReviewerACC InitiativesChief Pharmaceutic
Board of Academic Officer als
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Governors
Ehrin J. Organizational University of Abbott None None None None None
Armstrong ReviewerSVM ColoradoDirector, Medtronic
EP
Interventional Merck
Cardiology Spectranetics
Bernadette Organizational Loyola University None None None None None None
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Director, Division of
Vascular Surgery and
Endovascular Therapy;
Associate Professor,
Department of Surgery;
Program Director,
Vascular Surgery
Fellowship; Medical
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Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
Director, Vascular
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Noninvasive lab
Alison Organizational University of Tennessee None None None CSL Behring AACVPR None
Bailey Reviewer Chattanooga ZOLL Medical
RI
AACVPR Cardiologist
Todd Brown Organizational University of Alabama None None None Amgen* None None
Reviewer at Birmingham Omthera
SC
AACVPR Associate Professor NIH*
Kristen Organizational University of Maryland None None None None None None
Columbia ReviewerSVN Baltimore Washington
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Medical Center,
Maryland Vascular
AN
CenterNurse
practitioner
Michael S. Organizational University of California Cook Medical None None Bard University of None
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Conte ReviewerSVS San Francisco Medtronic California
Professor and Chief Department of
Surgery
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Alik Farber Organizational Boston Medical Bard None None None None None
Reviewer CenterChief,
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SCVS Division of Vascular
Surgery
Robert Organizational University of Florida Cook None None Cook Medical Cook Medical Defendant,
EP
Feezor Reviewer Associate Professor of Medical* Novate peripheral
VESS Surgery, Division of Medtronic angioplasty,
Vascular Surgery and Terumo 2015
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Endovascular Therapy
Dmitriy N. Organizational Weill Cornell Medical AstraZeneca Abbott None None Biotronic None
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Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
The
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Medicines
Company
Jonathan Organizational James Cook None None None James Cook None None
RI
Golledge Reviewer UniversityProfessor, University*
TASC Department of Surgery,
Head of Vascular
SC
Biology Unit
Bruce H. Organizational Greenville Health None Medtronic None Abbott NCDR None
Gray Reviewer SystemDirector of W.L. Gore ACC
U
SCAI Clinical Trials,
Department of Surgery
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William R. Organizational Colorado Prevention None None None AstraZeneca* CPC Clinical None
Hiatt Reviewer CenterProfessor of Bayer * Research*
TASC Medicine CSI NIH*
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Kowa
Kyushu
University
D
Merck
Pluristem*
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ReNeuron
Joseph Mills Organizational Baylor College of None None None None AnGes None
ReviewerSVS MedicineProfessor Bayer
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and Chief, Division of Cesca
Vascular surgery and
Endovascular Therapy
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Mohammad Organizational University of Colorado None None None None None None
Reza Rajebi ReviewerSIR DenverAssistant
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Professor
Mitchell J. Organizational McConnell Heart Boston Bristol-Myers Contego None W.L. Gore None
Silver ReviewerSVM Hospital for Critical Scientific Squibb* Medical* Medtronic
Limb CareDirector of W.L. Gore Pfizer* NIH
Vascular Imaging Medtronic
Lily Organizational Hpital St-Boniface None None None None None None
Thomson ReviewerSVN HospitalClinical
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 63
ACCEPTED MANUSCRIPT
Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
Research Coordinator,
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Vascular Surgery
Nurse, Section of
Vascular Surgery,
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Health Sciences Centre
Sana M. Al- Content Duke Clinical Research None None None FDA* HRS (Board of None
Khatib Reviewer InstituteAssociate NHLBI* Trustees)
SC
ACC/AHA Task Professor of Medicine PCORI* Elsevier*
Force on Clinical VA (DSMB)
Practice
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Guidelines
Herbert Content Rhode Island None None None Silk Road Bard
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Aronow ReviewerACC HospitalDirector of Medical NIH
Peripheral Cardiac Catheterization Saint Luke's PCORI
Vascular Disease Laboratories Health System SVM
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Member Section The Medicines W.L. Gore
Company
Joshua A. Content Vanderbilt University AstraZeneca* None EMX Bristol-Myers Vascular Defendant,
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Beckman Reviewer Medical Center Merck* JanaCare Squibb* Interventional venous
Director Sanofi* Merck* Advances thrombo-
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NIH embolism,
2015*
James C. Content Geisinger Medical None None None Abbott SCAI (Past None
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Blankenship Reviewer CenterStaff AstraZeneca President)
Physician; Director, Boston Scientific AMA
Cardiac Catheterization GlaxoSmithKline
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Medinal LTD
Orexigen
Therapeutics
St. Jude Medical
Stentys
Takeda
Pharmaceuticals
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 64
ACCEPTED MANUSCRIPT
Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
Biykem Content Michael E. DeBakey None None None Novartis None None
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Bozkurt Reviewer VA Medical Center
ACC/AHA Task The Mary and Gordon
Force on Clinical Cain Chair and
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Practice Professor of Medicine
Guidelines
Joaquin E. Content Oregon Health and None None None None ACC/AHA None
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Cigarroa Reviewer Science University AHA
ACC/AHA Task Clinical Professor of ASA
Force on Clinical Medicine Catheterization
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Practice and
Guidelines Cardiovascular
AN
Intervention
Portland Metro
Area AHA
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(President)
SCAI Quality
Interventional
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Council
NIH
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Federico Content Centro Medico None None None None None None
Gentile Reviewer DiagnosticoDirector,
ACC/AHA Task Cardiovascular Disease
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Force on Clinical
Practice
Guidelines
Seimens* Direct Flow
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Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
Alan Hirsch Content University of Merck* None none Bayer * AHA None
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Reviewer Minnesota Medical Novartis Pluristem (PLX- Tactile Medical*
SchoolProfessor of PAD trialPI)
Medicine, AstraZeneca
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Epidemiology and (EUCLID trial
Community Health, and PI)
Director Vascular Pluristem*
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Medicine Program
Mark A. Content Stanford University Acumen* None None Blue Cross/Blue ACC (Associate None
Hlatky Reviewer School of Medicine Genentech Shield Center for Editor)*
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ACC/AHA Task Professor of Health Effectiveness
Force on Clinical Research and Policy, Evaluation*
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Practice Professor of Medicine George Institute
Guidelines HeartFlow*
NHLBI
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Sanofi-aventis
Michael R. Content Newton-Wellesley AOPA None MC10 Abbott CBSET None
Jaff Reviewer Hospital; Harvard Cardinal Janacare Boston Scientific Intersocietal
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Medical School Health Northwind Cordis Accreditation
Professor of Medicine Covidien PQ Bypass IC Sciences Commission
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Micell Primacea Medtronic SCAI
Vascular SanoV Novello VIVA Physicians
Therapies Valiant Group*
EP
Medical
Jos A. Content UT Southwestern None None None None None None
Joglar Reviewer Medical Center
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Practice Cardiac
Guidelines Electrophysiology
Fellowship Program
Director
Glenn N. Content Baylor College of None None None None None None
Levine Reviewer MedicineProfessor of
ACC/AHA Task Medicine; Director,
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 66
ACCEPTED MANUSCRIPT
Reviewer Representation Employment Consultant Speakers Ownership/ Personal Research Institutional, Expert
Bureau Partnership/ Organizational, or Witness
Principal Other Financial
Benefit
Force on Clinical Cardiac Care Unit
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Practice
Guidelines
Khusrow Content Emory University None Medtronic* None Bard None Plaintiff,
RI
Niazi ReviewerACC Department of Impeto MI
Peripheral MedicineAssociate Terumo resulting in
Vascular Disease Professor of Medicine death,
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Member Section 2015*
Paul D. Content VA Eastern Colorado None None None VA Health AHA (Guest None
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Varosy ReviewerTask Health Care System Services Research Editor)
Force on Associate Professor and Development
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Performance (PI)*
Measures
Christopher Content Ochsner Clinical Neovasc None None AstraZeneca ACE (Board of None
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J. White Reviewer School, University of Pharmaceuticals Directors)
Queensland NIH
Chairman, Department Neovasc
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of Cardiology Surmodics
This table represents all relationships of reviewers with industry and other entities that were reported by authors, including those not deemed to be relevant to this document, at the
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time this document was under development. The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant
interest in a business if the interest represents ownership of 5% of the voting stock or share of the business entity, or ownership of $5,000 of the fair market value of the business
entity; or if funds received by the person from the business entity exceed 5% of the persons gross income for the previous year. Relationships that exist with no financial benefit are
EP
also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Please refer to http://www.acc.org/guidelines/about-guidelines-and-
clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing
Committees.
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*Significant relationship.
No financial benefit.
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AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; ACC, American College of Cardiology; ACE, Accreditation for Cardiovascular
Excellence; AHA, American Heart Association; AMA, American Medical Association; DSMB, data and safety monitoring board; EUCLID, Effects of Ticagrelor and
Clopidogrel in Patients with Peripheral Artery Disease; FDA, U.S. Food and Drug Administration; HRS, Heart Rhythm Society; MI, myocardial infarction; NCDR, National
Cardiovascular Data Registry; NIH, National Institutes of Health; NHLBI, National Heart, Lung, and Blood Institute; PCORI, Patient-Centered Outcomes Research
Institute; PI, primary investigator; PLX-PAD, placental-derived adherent stromal cell; SCAI, Society for Cardiovascular Angiography and Interventions; SCVS, Society for
Clinical Vascular Surgery; SIR, Society of Interventional Radiology; SVM, Society for Vascular Medicine; SVN, Society for Vascular Nursing; SVS, Society for Vascular
2016 by the American Heart Association, Inc. and American College of Cardiology Foundation 67
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Surgery; TASC, Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease; VA, Veterans Affairs; VESS, Vascular and Endovascular
Surgery Society; and VIVA, Vascular Intervention Advances.
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2016 AHA/ACC Lower Extremity PAD Guideline
Appendix 3. Abbreviations
AAA = abdominal aortic aneurysm
ABI = ankle-brachial index
ALI = acute limb ischemia
CAD = coronary artery disease
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CLI = critical limb ischemia
CTA = computed tomography angiography
DAPT = dual-antiplatelet therapy
DES = drug-eluting stent(s)
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GDMT = guideline-directed management and therapy
MI = myocardial infarction
MRA = magnetic resonance angiography
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PAD = peripheral artery disease
PTA = percutaneous transluminal angioplasty
RCT = randomized controlled trial
SPP = skin perfusion pressure
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TBI = toe-brachial index
TcPO2 = transcutaneous oxygen pressure
QoL = quality of life
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