Eur J Vasc Endovasc Surg (xxxx) xxx, xxx

CLINICAL PRACTICE GUIDELINE DOCUMENT

The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease

in People With Diabetes Mellitus and a Foot Ulcer
Robert Fitridge a,*, Vivienne Chuter b, Joseph Mills c, Robert Hinchliffe d, Nobuyoshi Azuma e, Christian-Alexander Behrendt f, Edward J. Boyko g,
Michael S. Conte h, Misty Humphries i, Lee Kirksey j, Katharine C. McGinigle k, Sigrid Nikol l, Joakim Nordanstig m, Vincent Rowe n, David Russell o,
Jos C. van den Berg p, Maarit Venermo q, Nicolaas Schaper r
a
Faculty of Health and Medical Sciences, University of Adelaide and Vascular and Endovascular Service, Royal Adelaide Hospital Adelaide, Australia
b
School of Health Sciences, Western Sydney University, Campbelltown, Australia
c
Baylor College of Medicine, Houston, TX, USA
d
Bristol Centre for Surgical Research, University of Bristol, Bristol, UK
e
Asahikawa Medical University, Hokkaido, Japan
f
Department of Vascular and Endovascular Surgery, Asklepios Clinic Wandsbek, Asklepios Medical School, Hamburg, Germany
g
University of Washington, Seattle, WA, USA
h
University of California, San Francisco Medical Centre, CA, USA
i
UC Davis Medical Centre, Sacramento, CA, USA
j
The Cleveland Clinic, Cleveland, OH, USA
k
University of North-Carolina, Chapel Hill, NC, USA
l
Clinical and Interventional Angiology, Asklepios Klinik, St Georg, Hamburg, Germany
m
Sahlgrenska University Hospital, Gothenburg, Sweden
n
David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
o
Leeds Teaching Hospitals NHS Trust, Leeds, UK
p
CENTRO VASCOLARE TICINO Ospedale Regionale di Lugano, sede Civico and Universitätsinstitut für Diagnostische, Interventionelle und Pädiatrische Radiologie
Inselspital, Universitätsspital Bern Switzerland
q
Helsinki University Hospital, University of Helsinki, Helsinki, Finland
r
Division of Endocrinology, Dept. Internal Medicine, MUMCþ, The Netherlands

Abstract: Diabetes related foot complications have become a major cause of morbidity and are implicated in most
major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral
artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events.
The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the
management and prevention of diabetes related foot complications since 1999. This guideline is an update of the
2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with
diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular
Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of
recommendations relevant to clinicians in all countries.
This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment,
Development and Evaluation framework clinically relevant questions were formulated, and the literature was
systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated
which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability,
equity, resources required, and when available, costs.
Through this process five recommendations were developed for diagnosing PAD in a person with diabetes,
with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to
estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or
gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of
people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing
Committee has highlighted key research questions where current evidence is lacking.
The Writing Committee believes that following these recommendations will help healthcare professionals to
provide better care and will reduce the burden of diabetes related foot complications.
Keywords: Chronic limb threatening ischaemia, Critical limb ischaemia, Diabetes mellitus, Diabetes related foot ulcer, Endovascular intervention,
Peripheral artery disease
Available online XXX
Ó The Author(s). Published by Elsevier Inc. on behalf of The Society for Vascular Surgery, Elsevier B.V on behalf of European Society for Vascular
Surgery and John Wiley & Sons Ltd.
* Corresponding author.
E-mail address: robert.fi[email protected] (Robert Fitridge).
1078-5884/Ó The Author(s). Published by Elsevier Inc. on behalf of The Society for Vascular Surgery, Elsevier B.V on behalf of European Society for Vascular
Surgery and John Wiley & Sons Ltd.
https://doi.org/10.1016/j.ejvs.2023.07.020

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
2 Robert Fitridge et al.

TABLE OF CONTENTS
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
List of Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
External experts, patient representatives and review process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Target population and target audience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6
Guideline writing group conflict of interest policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
Definitions and terminology as used in this document . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8
Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Future research priorities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Contribution of authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

ABBREVIATIONS GVG Global Vascular Guidelines

ABI Ankle brachial index HbA1c Haemoglobin A1c
ADA American Diabetes Association IDSA Infectious Diseases Society of America
AP Ankle pressure IWGDF International Working Group on the Diabetic
CDUS Colour Duplex ultrasound Foot
CI Confidence interval LDL Low density lipoproteins
CLTI Chronic limb threatening ischaemia MAC Medial arterial calcification
COI Conflict of interest MACE Major adverse cardiovascular events
CTA Computed tomography angiography MALE Major adverse limb events
CWD Continuous wave Doppler MRA Magnetic resonance angiography
DFU Diabetes related foot ulcer NLR Negative likelihood ratio
DSA Digital subtraction angiography PAD Peripheral artery disease
EAS European Atherosclerosis Society PICO Population, Intervention, Comparison, Outcome
EASD European Association for the Study of PLR Positive likelihood ratio
Diabetes SGLT-2 Sodiumeglucose cotransporter 2
eGRF Estimated glomerular filtration rate SPP Skin perfusion pressure
ESC European Society of Cardiology SVS Society for Vascular Surgery
ESVM European Society of Vascular Medicine TBI Toe brachial index
ESVS European Society for Vascular Surgery TcPO2 Transcutaneous oxygen pressure
GLASS Global Limb Anatomic Staging System TP Toe pressure
GRADE Grading of Recommendations, Assessment, WIfI Wound/Ischaemia/foot Infection
Development and Evaluation WFVS World Federation of Vascular Societies

LIST OF RECOMMENDATIONS

Summary of recommendations

Chapter Recommendation Grade Certainty of

evidence
Diagnosis 1. In a person with diabetes without a foot ulcer, take a relevant history for Strong Low
peripheral artery disease, examine the foot for signs of ischaemia and
palpate the foot pulses at least annually, or with any change in clinical
status of the feet.

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 3

-continued
Chapter Recommendation Grade Certainty of
evidence
2. In a person with diabetes without a foot ulcer, if peripheral artery Conditional Low
disease (PAD) is suspected, consider performing pedal Doppler
waveforms in combination with ankle brachial index (ABI) and toe
brachial index (TBI). No single modality has been shown to be optimal
for the diagnosis of PAD and there is no value above which PAD can be
excluded. However, PAD is less likely in the presence of ABI 0.9 e 1.3;
TBI  0.70; and triphasic or biphasic pedal Doppler waveforms.

3. In a person with diabetes and a foot ulcer or gangrene, take a relevant Strong Low
history for peripheral artery disease, examine the person for signs of
ischaemia and palpate the foot pulses.

4. In a person with diabetes and a foot ulcer or gangrene, evaluate pedal Strong Low
Doppler waveforms in combination with ankle brachial index (ABI)
and toe brachial index (TBI) measurements to identify the presence of
peripheral artery disease (PAD).
No single modality has been shown to be optimal for the diagnosis of
PAD, and there is no value above which PAD can be excluded. However,
PAD is less likely in the presence of ABI 0.9 e 1.3; TBI  0.70; and
triphasic or biphasic pedal Doppler waveforms.

5. In a person with diabetes without a foot ulcer in whom a non- Best Practice Statement
emergency invasive foot procedure is being considered, peripheral
artery disease should be excluded by performing assessment of pedal
Doppler waveforms in combination with ankle brachial index and toe
brachial index.

Prognosis 6. In a person with diabetes and a foot ulcer or gangrene, consider Conditional Low
performing ankle pressures and ankle brachial index (ABI)
measurements to assist in the assessment of likelihood of healing and
amputation.
Ankle pressure and ABI are weak predictors of healing. A low ankle
pressure (e.g., < 50 mmHg) or ABI (e.g., < 0.5) may be associated with
a greater likelihood of impaired healing and greater likelihood of major
amputation.

7. In a person with diabetes and a foot ulcer or gangrene, consider Conditional Low
performing a toe pressure measurement to assess likelihood of healing
and amputation.
A toe pressure  30 mmHg increases the pre-test probability of healing
by up to 30% and a value < 30 mmHg increases the pre-test probability
of major amputation by approximately 20%.

8. In a person with diabetes and a foot ulcer or gangrene, if a toe pressure Conditional Low
cannot be performed, consider performing a transcutaneous oxygen
pressure (TcPO2) measurement or a skin perfusion pressure (SPP) to
assess likelihood of healing.
A TcPO2  25 mmHg increases the pre-test probability of healing by up
to 45% and value < 25 mmHg increases the pre-test probability of
major amputation by approximately 20%. An SPP  40 mmHg increases
the pre-test probability of healing by up to 30%.

9. In a person with diabetes and a foot ulcer or gangrene, it is suggested Conditional Low
that the presence of peripheral artery disease and other causes of
poor healing should always be assessed. Diabetes related micro-
angiopathy should not be considered the primary cause of foot
ulceration, gangrene, or poor wound healing without excluding other
causes.

Continued

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
4 Robert Fitridge et al.

-continued
Chapter Recommendation Grade Certainty of
evidence
10. In a person with diabetes, peripheral artery disease and a foot ulcer or Conditional Low
gangrene, consider using the Wound/Ischaemia/foot Infection (WIfI)
classification system to estimate healing likelihood and amputation risk.

Treatment 11. In a person with diabetes, peripheral artery disease, and a foot ulcer or Best Practice Statement
gangrene who is being considered for revascularisation, evaluate the
entire lower extremity arterial circulation (from aorta to foot) with
detailed visualisation of the below knee and pedal arteries.

12. In a person with diabetes, peripheral artery disease, a foot ulcer, and Best Practice Statement
clinical findings of ischaemia, a revascularisation procedure should
be considered. Findings of ischaemia include absent pulses,
monophasic or absent pedal Doppler waveforms, ankle pressure < 100
mmHg or toe pressure < 60 mmHg. Consult a vascular specialist unless
major amputation is considered medically urgent.

13. In a person with diabetes, peripheral artery disease, a foot ulcer, and Best Practice Statement
severe ischaemia i.e., an ankle brachial index < 0.4, ankle pressure
< 50 mmHg, toe pressure < 30 mmHg or transcutaneous oxygen
pressure < 30 mmHg or monophasic or absent pedal Doppler
waveforms, urgently consult a vascular specialist regarding possible
revascularisation.

14. In a person with diabetes, peripheral artery disease, and a foot ulcer Best Practice Statement
with infection or gangrene involving any portion of the foot,
urgently consult a vascular specialist in order to determine the timing
of a drainage procedure and a revascularisation procedure.

15. In a person with diabetes and a foot ulcer, when the wound Best Practice Statement
deteriorates or fails to significantly improve (e.g., a less than 50%
reduction in wound area within four weeks) despite appropriate
infection and glucose control, wound care, and offloading, reassess the
vascular status and consult with a vascular specialist regarding
possible revascularisation.

16. In a person with diabetes, peripheral artery disease, and a foot ulcer or Best Practice Statement
gangrene, avoid revascularisation when the riskebenefit ratio for the
probability of success of the intervention is clearly unfavourable.

17. In a person with diabetes, peripheral artery disease, and a foot ulcer or Conditional Moderate
gangrene who has an adequate single segment saphenous vein in
whom infrainguinal revascularisation is indicated and who is suitable
for either approach, consider bypass in preference to endovascular
therapy.

18. A person with diabetes, peripheral artery disease (PAD), and a foot Best Practice Statement
ulcer or gangrene, should be treated in a centre with expertise in, or
rapid access to, endovascular and surgical bypass revascularisation. In
this setting, consider making treatment decisions based on the risk to
and preference of the individual, limb threat severity, anatomical
distribution of PAD, and the availability of autogenous vein.

19. In a person with diabetes, peripheral artery disease, and a foot ulcer or Best Practice Statement
gangrene, revascularisation procedures should aim to restore in line
blood flow to at least one of the foot arteries.

20. In a person with diabetes, peripheral artery disease, and a foot ulcer or Conditional Very low
gangrene undergoing an endovascular procedure, consider targeting
the artery on angiography that supplies the anatomical region of the
ulcer, when possible or practical.

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 5

-continued
Chapter Recommendation Grade Certainty of
evidence
21. In a person with diabetes and either a foot ulcer or gangrene who has Best Practice Statement
undergone revascularisation, objectively assess adequacy of perfusion
e.g., using non-invasive bedside testing.

22. A person with diabetes, peripheral artery disease, and either a foot Best Practice Statement
ulcer or gangrene should be treated by a multidisciplinary team as
part of a comprehensive care plan.

23. In a person with diabetes and peripheral artery disease the following Best Practice Statement
target levels should be:
HbA1c < 8% (< 64 mmol/mol), but higher target HbA1c value may
be necessary depending on the risk of severe hypoglycaemia.
Blood pressure < 140/ 90 mmHg but higher target levels may be
necessary depending on the risk of orthostatic hypotension and other
side effects.
Low density lipoprotein target of < 1.8 mmol/L (< 70 mg/dL) and
reduced by at least 50% of baseline. If high intensity statin therapy
(with or without ezetimibe) is tolerated, target levels < 1.4 mmol/L
(55 mg/dL) are recommended.

24. In a person with diabetes and symptomatic peripheral artery disease: Best Practice Statement
treatment with single antiplatelet therapy should be used,
treatment with clopidogrel should be considered as first choice in
preference to aspirin,
combination therapy with aspirin (75 mg to 100 mg once daily) plus
low dose rivaroxaban (2.5 mg twice daily) should be considered for
people without a high bleeding risk.

25. In a person with type 2 diabetes and peripheral artery disease: Best Practice Statement
with an eGFR > 30 mL/min/1.73m2, a sodium glucose cotransporter-
2 (SGLT-2) inhibitor or a glucagon like peptide 1 receptor agonist
with demonstrated cardiovascular disease benefit should be
considered, irrespective of the blood glucose level.
SGLT-2 inhibitors should not be started in drug naïve people with a
diabetes related foot ulcer or gangrene and temporary
discontinuation should be considered in people already using these
drugs, until the affected foot is healed.

EXTERNAL EXPERTS, PATIENT REPRESENTATIVES AND for the first time in late 2020 and the first draft of the guideline
REVIEW PROCESS was sent out for review in December 2022.
The review process had several steps, in which six external
experts, four patient representatives, and guideline reviewers METHODOLOGY
of the International Working Group on the Diabetic Foot This guideline is also part of a set of guidelines (and their
(IWGDF), European Society for Vascular Surgery (ESVS), and supporting systematic reviews) of the IWGDF on the man-
Society for Vascular Surgery (SVS) were involved. The external agement of diabetes related foot ulcers, which all used the
experts and patient representatives were from various coun- same Grading of Recommendations, Assessment, Develop-
tries and continents (Singapore, Japan, South Africa, China, ment and Evaluation (GRADE) methodology. These guide-
Hong Kong, Colombia, Bulgaria, Australia, England, the USA). lines address the other aspects of management and are
The process started with review of the clinical questions that published separately. The IWGDF editorial board had the
the Writing Committee proposed to address, which were task of ensuring that there would not be too much overlap
subsequently adjusted, and which formed the basis of the between these documents and that they were consistent
guideline development. The first preliminary version of the with each other. The ESVS and SVS Executive Board agreed
guideline was reviewed by the IWGDF, ESVS, and members of with this approach. The methodology used is described in
the SVS Document Oversight Committee. The revised text was detail in a separate IWGDF document (https://doi.org/10.
then reviewed by the external experts and patient represen- 1002/dmrr.3656); here a summary is provided.1
tatives, and subsequently a new version was submitted for In brief, the GRADE system was followed.2,3 GRADE is
review to the three organisations.The Writing Committee met structured by the development of clinical questions and
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
6 Robert Fitridge et al.

selection of critical outcomes, which are subsequently trans- Conditional. All Writing Committee members voted on each
lated in the PICO (Population, Intervention, Comparison, recommendation. For a Strong Recommendation at least 75%
Outcome) format. The Writing Committee developed the and for a Conditional Recommendation at least 60% had to
clinical questions to be investigated after consultation with the agree. After each recommendation, a rationale is provided for
external experts and patient representatives. Critically how each recommendation was determined.1,14
important outcomes for clinical questions were voted upon by There were situations where sufficient direct evidence
the Writing Committee members. Subsequently, the PICOs supporting the formulation of a recommendation could not be
were created and voted on for inclusion by Writing Committee identified, but performing the actions recommended would
members.The PICOs to be included were then reviewed by the very likely result in clear benefit, or not performing the test or
external experts, patient representatives, and the guideline intervention in marked harm. In these situations, an ungraded
committee of the societies involved.The systematic reviews of Best Practice Statement was formulated with a rationale
the literature to address the clinical questions were performed explaining how the statement was arrived at and how GRADE
according to the preferred reporting items for systematic re- criteria for developing such a statement were considered, as
views and meta-analyses (PRISMA) guideline.4 The process of advised in a recent publication of the GRADE group on this
identifying and evaluating the available evidence, with its topic.15 According to GRADE, such recommendations should
main conclusions, resulted in three systematic reviews on be formulated as actionable statements when they are
Diagnosis, on Prognosis, and on Management of Peripheral deemed necessary for practice and when the desirable effects
Arterial Disease in Diabetes Mellitus.These systematic reviews of an intervention clearly outweigh its undesirable effects.
are published separately (https://doi.org/10.1002/dmrr.3683, Although in these cases direct evidence is lacking, they should
https://doi.org/10.1002/dmrr.3701, https://doi.org/10.1002/ be supported by indirect evidence. For the clinical question on
dmrr.3700).5-7 The population of interest was people with the use of current medical therapies to reduce cardiovascular
diabetes mellitus (with or without a foot ulcer or gangrene, risk or lower limb events in people with diabetes and symp-
depending on the clinical question). For diagnosis, the inter- tomatic peripheral artery disease (PAD), the authors did not
vention was any non-invasive bedside test and the comparator perform a systematic review or develop graded recommen-
an objective imaging study; for prognosis the intervention was dations, as recent high quality guidelines on these topics
any non-invasive bedside test and for treatment the in- already exist.16e23 However, to give the reader a complete
terventions were bypass (open) and direct revascularisation overview a summary of these existing guidelines was created,
and the comparators endovascular and indirect revascular- where relevant for the clinical question, and adapted to the
isation, respectively. The primary outcomes were wound person with diabetes mellitus and symptomatic PAD. These
healing, minor and major amputation and adverse events, recommendations were also formulated as Best Practice State-
limb salvage, and wound healing. After the literature search all ments. It is acknowledged that for certain recommendations
abstracts and subsequently selected articles were reviewed by high quality evidence exists, as summarised in other guidelines
two authors, as described in the systematic reviews. Included of organisations such as ESVS, SVS and American Diabetes As-
studies had at least 80% of participants with diabetes or in sociation, but for others there is only lesser quality evidence. In
which the results of the participants with diabetes were re- order not to repeat all these evidence based guidelines already
ported separately. All included studies were assessed for developed by other relevant organisations, ungraded Best
quality and risk of bias with the following instruments, Practice Statements were made, with references provided to the
depending on the type of study: Quality in Prognosis Studies, relevant guidelines. Finally, the Writing Committee considered
the revised quality appraisal tool for studies of diagnostic topics for future research and voted to focus on five key topics,
reliability, ROBINS-I (for assessing risk of bias in non- which are discussed at the end of the guideline.
randomised studies of interventions), the Newcastle-Ottawa The recommendations and corresponding rationales
Scale (for non-randomised studies, including observational were reviewed by the same international external experts
and cohort studies where details regarding allocation to and committees responsible for guideline development of
intervention groups was not provided), and the Cochrane risk the three aforementioned societies. Further details are
of bias 2 tool for randomised controlled trials.8e13 For each provided in the IWGDF guidelines methodology document.1
PICO the quality of evidence was graded for risk of bias, The summary of judgements tables that were the basis for
inconsistency, imprecision, publication bias, and overall qual- formulating each recommendation and Best Practice
ity. The certainty of the evidence was then rated as high, Statement, can be found in the Supplementary material
moderate, low, or very low. for this article. These systematic reviews provide the evi-
The GRADE evidence to decision approach was subse- dence for the graded recommendations made in this
quently used for the development of the recommendations guideline.
during online discussions of the Writing Committee (which
were all recorded and available for later review from the TARGET POPULATION AND TARGET AUDIENCE
Secretary). In developing each recommendation and its Poorly healing foot ulcers or gangrene in people with dia-
strength the following aspects were taken into account: betes mellitus are frequently caused by several factors
benefits, harms, effect size, and certainty; balance of benefits acting in concert. The primary target population of this
and harms; resource use; acceptability; feasibility; equity. The guideline is people with diabetes mellitus with a foot ulcer
strength of each recommendation was graded as Strong or or gangrene on any portion of the foot (with or without
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 7

neuropathy) in whom the presence of PAD could have Chronic limb threatening ischaemia: a clinical syndrome
contributed to the development of the ulcer and or its poor defined by the presence of peripheral artery disease in
healing potential. The secondary target group is people with combination with rest pain, gangrene, or foot ulcer of at
diabetes mellitus in whom the presence of PAD was least two weeks’ duration. Venous, embolic, non-
considered or needed to be excluded. People with pure atherosclerotic, and traumatic aetiologies are excluded.
venous ulcers, ulcers above the ankle, acute limb ischaemia, Diabetes related micro-angiopathy: pathological struc-
embolic disease, and non-atherosclerotic chronic vascular tural and functional changes in the microcirculation of
conditions of the lower extremity were excluded. people with diabetes mellitus, which can occur in any part
The primary target audience of this guideline is vascular of the body as a consequence of the disease.
specialists and all other healthcare professionals who are Diabetes related foot ulcer: a break of the skin of the foot
involved in the diagnosis, management, and prevention of that involves, as a minimum, the epidermis and part of the
diabetes related foot ulcers and gangrene, who work in dermis in a person with diabetes and usually accompanied
primary, secondary, and tertiary care. by neuropathy and or PAD in the lower extremity.
Patient representatives will be approached to discuss Diabetes related foot gangrene: a condition that occurs
which elements of the guideline should be included in the when body tissue dies because of insufficient blood supply,
Information for Patients. This will result in a list of items that infection, or injury.
should be addressed in this information. Given cultural and Foot perfusion: tissue perfusion strictly means the vol-
language differences, the final text should be produced on a ume of blood that flows through a unit of tissue and is often
national or local level. expressed in mL blood/100 g of tissue. With respect to
clinical assessment of the foot, perfusion is traditionally
GUIDELINE WRITING GROUP CONFLICT OF INTEREST measured by the surrogate markers of systolic arterial
POLICY pressure at the level of the ankle and toe arteries. Pressure
The three organisations participating in this guideline are measurements may be misleading in people with diabetes
committed to developing trustworthy clinical practice guide- due to the frequent presence of medial calcification. This
lines through transparency and full disclosure by those has led to the development of a number of alternative
participating in the process of guideline development. To clinically used means of assessing tissue perfusion, including
prevent a major Conflict of Interest (COI), members of the TcPO2 (transcutaneous pressure of oxygen), SPP (skin
Writing Committee were not allowed to serve as an officer, perfusion pressure), PAT (pedal acceleration time), and near
board member, trustee, owner, or employee of a company infrared spectrophotometry (NIRS).
directly or indirectly involved in the topic of this guideline. Multidisciplinary team: a group of people from relevant
Before the first and last meeting of the Writing Committee, clinical disciplines, whose interactions are guided by specific
members were asked to report any COI in writing. In addition, team functions and processes to achieve team and person
at the beginning of each meeting this question was also asked defined favourable outcomes.
and if answered yes, the members were asked to submit an Peripheral artery disease (PAD): obstructive atheroscle-
updated COI form. These COIs included income received from rotic vascular disease of the arteries from aorta to foot with
biomedical companies, device manufacturers, pharmaceutical clinical symptoms, signs, or abnormalities on non-invasive
companies, or other companies producing products related to or invasive vascular assessment, resulting in disturbed or
the field. In addition, industry relationships had to be disclosed impaired circulation in one or more extremities.
each time and these included: ownerships of stocks or options
or bonds of a company, any consultancy, scientific advisory
committee membership, or lecturer for a company, research INTRODUCTION
grants, or income from patents.These incomes could either be The incidence of diabetes continues to increase in all
personal or obtained by an institution with which the member countries. Recent estimates are that 537 million people are
had a relationship. All disclosures were reviewed by the three affected by diabetes (1 in 11 adults worldwide) and that 783
organisations, and these can be found at IWGDFguidelines. million individuals will be affected by 2045.25 Diabetes is
org/. No company was involved in the development or re- associated with significant risk of foot complications
view of the guideline. Nobody else involved in the guideline including ulceration, gangrene, and amputation. Develop-
received any payment or remuneration of any costs. ment of diabetes related foot ulceration (DFU) precedes up
to 85% of non-traumatic amputations, with an annual
DEFINITIONS AND TERMINOLOGY AS USED IN THIS incidence of ulceration of approximately 2% and lifetime
DOCUMENT incidence of DFU up to 34%.26 Diabetes related complica-
The definitions and criteria for diabetes related foot disease tions in the lower limb, including peripheral neuropathy and
were standardised by the IWGDF and in parallel to this PAD, typically precede the development of DFU.27 Collec-
guideline an update is published.24 In addition, in this tively, these complications are a leading global cause of
guideline the following terminology was used: disability, hospitalisation, and amputation, with a high
Bedside testing: any non-invasive test assessing for PAD mortality rate following amputation.28
in the lower limb using a measure of blood flow that could Diabetes is a significant risk factor for development of
be conducted at the bedside. PAD. In a recent systematic review, Stoberock et al.29 found
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
8 Robert Fitridge et al.

that the prevalence of PAD was 10 e 26% in the general vary markedly between and within countries and this
adult population and 20 e 28% in those with diabetes. In guideline is a multinational initiative. However, emphasis is
those with DFU, the prevalence of PAD was 50%, which is given to which expertise should be present, in terms of
consistent with the findings of the multicentre Eurodiale knowledge, skills, and competence, to manage people
study.29,30 PAD in people with diabetes is characterised by a according to the expected standards of care.
disease pattern that is frequently multisegmental and
bilateral with impaired collateral formation, often long Related guidelines
segment tibial artery occlusions, and is more distally This guideline is also part of the IWGDF guidelines on the
distributed in the lower limb including frequent presenta- prevention and management of diabetes related foot disease.
tion of infragenicular arterial occlusive disease, with an Management of PAD in these people without addressing the
increased risk of amputation.31e33 The diagnosis of PAD and other aspects of DFU treatment will frequently result in sub-
chronic limb threatening ischaemia (CLTI) is frequently optimal outcomes. The reader is therefore referred to the other
complicated by the absence of classical symptoms of PAD IWGDF guidelines for these aspects. This IWGDF, ESVS, SVS
such as intermittent claudication and rest pain, probably intersocietal guideline on PAD in people with diabetes mellitus
due to factors such as sedentary lifestyle and loss of pain is also part of the IWGDF guidelines on the management of
sensation due to diabetes related peripheral neuropathy, diabetes related foot complications with additional chapters on
which is present in the majority of people with an Classification (https://doi.org/10.1002/dmrr.3648),38 Preven-
(ischaemic) DFU.30,32 Co-existent medial artery calcification tion (https://doi.org/10.1002/dmrr.3651),39 Offloading (https://
(MAC), which is also associated with peripheral neuropathy, doi.org/10.1002/dmrr.3647),40 Infection (https://doi.org/10.
is common and can affect the accuracy of non-invasive tests 1002/dmrr.3687),104 Charcot (https://doi.org/10.1002/dmrr.
such as the ankle brachial index (ABI) by causing elevation 3646),41 and Wound healing (https://doi.org/10.1002/dmrr.
of ankle and, to a lesser extent, digital pressures.34 3644).42 These guidelines are summarised for daily clinical
In people with diabetes early diagnosis of PAD is essen- use in the Practical Guidelines on the Prevention and Man-
tial.29 The disease process is associated with greater likeli- agement of Diabetes Related Foot Disease (https://doi.org/10.
hood of delayed or non-healing of DFU, gangrene, and 1002/dmrr.3657).43 This guideline builds on a previous version
amputation in addition to increased rates of cardiovascular of the IWGDF guideline on peripheral artery disease in patients
morbidity and mortality.35 The prognosis of a person with with foot ulcers and diabetes, and integrates with the Global
diabetes, PAD, and foot ulceration requiring amputation is Vascular Guidelines (GVG) on the management of Chronic Limb
worse than for many common cancers, up to 50% of people Threatening Ischaemia.20,37
will not survive five years.26,36 PAD places the person at
very high risk of adverse cardiovascular events and thus
optimal medical management of cardiovascular risk factors DIAGNOSIS
should be ensured.32 Early and adequate assessment of foot
perfusion is necessary to ensure that elevated risk of Clinical question
delayed or poor wound healing and amputation is identified In a person with diabetes with or without a foot ulcer, does
early so this can be addressed without treatment delay. medical history and clinical examination (including pulse
Despite the severity of the outcomes of PAD in people palpation) compared with a reference test (imaging - digital
with diabetes, and particularly for those with DFU, there are subtraction angiography [DSA], magnetic resonance angi-
few practice guidelines that specifically address the diag- ography [MRA], computed tomography angiography [CTA],
nosis and management of PAD in this population. Formu- colour Duplex ultrasound [CDUS]) accurately identify and
lating recommendations for this specific population should reliably diagnose PAD?
take into account the multisystem nature of diabetes and
the impact of other diabetes complications on the utility of Clinical question
diagnostic tests, wound healing, amputation, and survival In a person with diabetes with or without a foot ulcer, which
outcomes. One of the guidelines that specifically addressed non-invasive bedside testing alone or in combination compared
these topics has been that of the IWGDF, with the last with reference tests (imaging - digital subtraction angiography
version produced in 2019.37 Instead of making a new [DSA], magnetic resonance angiography [MRA], computed to-
updated version, the IWGDF together with the ESVS and the mography angiography [CTA], colour Duplex ultrasound [CDUS])
SVS decided to collaborate in writing this new, intersociety, should be performed to accurately and reliably diagnose PAD?
practice guideline on PAD in diabetes mellitus, with
emphasis on people with diabetes related foot ulcers or
Recommendation 1
gangrene. The aim is to provide evidence based recom-
mendations on the diagnosis, prognosis (i.e., the prognostic In a person with diabetes without a foot ulcer, take a relevant
history for peripheral artery disease, examine the foot for
value of different non-invasive tests), and treatment of PAD signs of ischaemia and palpate the foot pulses at least
in people with a foot ulcer and diabetes. Each of these annually, or with any change in clinical status of the feet.
topics is discussed in the different sections below. It is not
Grade Certainty of evidence
the intention to detail the specific roles, tasks, and re-
sponsibilities of each medical specialty involved as these Strong Low

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 9

Although based on low quality evidence, data demon-

Recommendation 2
strating increased likelihood of PAD in those with weak or
In a person with diabetes without a foot ulcer, if peripheral absent pulses and elevated risk of cardiovascular
artery disease (PAD) is suspected, consider performing pedal
morbidity and mortality support the preference of a
Doppler waveforms in combination with ankle brachial index
(ABI) and toe brachial index (TBI). No single modality has person with diabetes for clinical examination including
been shown to be optimal for the diagnosis of PAD and there pulse palpation to be performed.35,5 The non-invasive
is no value above which PAD can be excluded. However, PAD nature of clinical examination and pulse palpation sug-
is less likely in the presence of ABI 0.9 e 1.3; TBI ‡ 0.70; and gest that these assessments would be valued by people
triphasic or biphasic pedal Doppler waveforms.
with diabetes as initial diagnostic tests. As equipment is
Grade Certainty of evidence not required, the Writing Committee considered pulse
Conditional Low palpation and other forms of clinical examination as
having low resource requirements, which can be applied
on a broad scale by a range of practitioners, and offer a
Rationale method to increase equity of healthcare access that is
Diagnosis and treatment of PAD is critical due to the both feasible for healthcare providers and acceptable for
increased risk of developing DFU as well as the increased people with diabetes. This Strong Recommendation is
rate of complications from co-existent cardiovascular therefore made, based on low certainty of evidence and
disease including myocardial infarction and stroke.35 Evi- expert opinion.
dence for the diagnostic accuracy of pulse palpation for Bedside testing techniques that provide objective mea-
PAD in people with diabetes without DFU is limited with surement of peripheral blood flow in the lower extremity
two studies of low quality demonstrating that although (e.g., ankle brachial index [ABI], toe brachial index [TBI],
presence of pulses does not exclude disease, there is a and pedal Doppler waveforms) have been shown to be
small increase in ability to rule disease in where a foot useful to diagnose and exclude PAD in people with dia-
pulse is absent or weak (positive likelihood ratio [PLR] betes. The systematic review demonstrates that multiple
1.84 e 2.46).44,45 The PLR gives the change in odds of bedside testing techniques that offer objective measure-
experiencing an outcome if the test is positive, whereas ment of the peripheral circulation in the lower limb are
the negative likelihood ratio (NLR) expresses a change in useful as a means to rule disease in or out for people with
odds of experiencing an outcome if the test is negative. A diabetes without a DFU but who are suspected of having
PLR or NLR of 1.0 means that the test does not change the PAD.5
probability of the outcome over and above the pre-test Forty studies investigating the diagnostic accuracy of
probability and therefore is not a useful diagnostic test. non-invasive bedside tests in populations with diabetes
However, it is important to recognise that pulse palpation were identified.5 Twenty eight of the studies used pro-
should be performed, and results considered in the spective recruitment and the remainder were retrospec-
context of other clinical examinations that may be asso- tive. Overall, the studies were of low quality and evidence
ciated with PAD including hair loss, muscle atrophy, and was judged as being of low certainty. Although it was not
reduced peripheral skin temperature. It should be noted possible to identify the absolute threshold or normal
that these clinical examinations are highly subjective and values of bedside tests, it is suggested that PAD is more
such findings may also be associated with neuropathy. likely to be present in this population with an ABI < 0.9 or
PAD may also be asymptomatic or have an atypical pre- > 1.3, a TBI < 0.70, and presence of one or more
sentation in people with diabetes as in other elderly or at monophasic Doppler waveforms from assessment of pedal
risk populations.27,46,47 For example, peripheral neuropa- arteries with continuous wave Doppler (CWD).5 In people
thy can mask pain symptoms and autonomic neuropathy without DFU, an ABI of < 0.90 is associated with a mod-
can result in a warm foot, meaning that the widely rec- erate to large increase in likelihood of PAD with PLRs
ognised signs and symptoms of PAD may not be ranging from 4.17 to 17.91; however, the ability to rule
present.48 disease out is variable (NLR 0 e 0.54) (Supplementary
These recommendations are applicable to all people with Table S1). A TBI < 0.70 has a moderate ability to di-
diabetes. When DFU is absent, but there are clinical signs agnose and exclude PAD (PLR 2.0 e 3.55, NLR 0.25 e 0.44),
and symptoms of PAD or PAD is suspected, for example due and the presence of a visual monophasic pedal Doppler
to long standing diabetes, chronic hyperglycaemia, other waveform (compared with a biphasic or triphasic Doppler
diabetes complications such as peripheral neuropathy, or waveform where the waveform crosses the zero flow
the presence of atherosclerotic disease in other vascular baseline and contains both forward and reverse velocity
beds, more frequent screening vascular assessment components)53 has a moderate ability to diagnose and
including additional bedside testing is necessary. These exclude PAD (PLR 7.09, NLR 0.19).
recommendations are consistent with other (inter)national Non-invasive bedside tests are therefore likely to be
guidelines on the management of diabetes, endorsing beneficial for people without a DFU; however, high quality
annual clinical assessment for PAD (and for other foot studies of diagnostic accuracy are required. A summary of
complications) in people with diabetes.49e52 results is provided in Supplementary Table S1.

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
10 Robert Fitridge et al.

When calculating the ABI in the leg of a person with and this group of people with asymptomatic disease. The role
without DFU for the purposes of diagnosing PAD, it is of additional testing in those with intermittent claudica-
advised to use the lower systolic blood pressure of either tion is outside the scope of this guideline.
the dorsalis pedis or posterior tibial artery as this improves
the diagnostic accuracy of the test.5 For PAD affecting ar- Recommendation 3
teries below the knee, this calculation method identifies the In a person with diabetes and a foot ulcer or gangrene, take a
most severe disease while using the higher pressure iden- relevant history for peripheral artery disease, examine the
tifies the least affected artery. Use of three tests (ABI, TBI, person for signs of ischaemia and palpate the foot pulses.
and pedal Doppler waveforms) is recommended. This is Grade Certainty of evidence
because the accuracy of the tests may be affected by the
Strong Low
presence of other diabetes related complications.
Due to the use of bedside measures to monitor PAD
status over time, reliability (or reproducibility) of the tests
is important in determining their clinical effectiveness. The
Recommendation 4
systematic review showed that the reliability of both the
ABI and TBI was good to excellent. However, these tests In a person with diabetes and a foot ulcer or gangrene,
are limited by wide margins of error, which affect the evaluate pedal Doppler waveforms in combination with
ankle brachial index (ABI) and toe brachial index (TBI)
amount of change required for this to be considered a true measurements to identify the presence of peripheral artery
change rather than related to error in the measurement. disease (PAD).
For example, an ABI measured by the same rater requires a No single modality has been shown to be optimal for the
change of 0.15 to be considered a true change.54 There- diagnosis of PAD, and there is no value above which PAD can
fore, care should be taken in performing the measurement be excluded. However, PAD is less likely in the presence of
ABI 0.9 e 1.3; TBI ‡ 0.70; and triphasic or biphasic pedal
to control for factors that may introduce error including Doppler waveforms.
incorrect positioning of the person being tested (this
should be horizontal supine) and incorrect testing pro- Grade Certainty of evidence
cedures (e.g., pre-test exercise, caffeine consumption, Strong Low
etc.).
The recommendation identifies the need to perform
bedside testing in people with diabetes in whom PAD is Rationale
suspected. In people with diabetes without a DFU, the PAD is present in approximately half of the people with a
presence of PAD will increase the risk of a future DFU and DFU.29,30 Therefore, in any person with diabetes and a foot
amputation. The presence of PAD will influence the fre- ulcer or gangrene, PAD should be considered and should be
quency of screening and the measures that can be safely excluded with the appropriate diagnostic strategies. Sub-
taken to reduce the risk of amputation, as described in the sequently, once diagnosed the second question is whether
Prevention Guidelines of the IWGDF (https://doi.org/10. the PAD is of sufficient severity to contribute to delayed
1002/dmrr.3651).39 It is therefore critical that, apart wound healing and increased risk of amputation. This will
from the history and foot examination, risk factors for PAD inform whether further investigation or intervention is
are also considered such as long standing or poorly required. In addition, although cardiovascular risk factor
controlled diabetes or diagnosis of atherosclerosis in other modification is always indicated in people with diabetes,
vascular beds. Considering the benefits and harms of this those with symptomatic PAD (i.e., including those with a
recommendation it is judged to be essential to diagnose or DFU) belong to the very high cardiovascular risk category
exclude PAD in this population given the large impact of and need more intensive risk treatment, as described in the
untreated disease, the low burden of the tests to the ‘Treatment’ section.
person undergoing testing, and the high likelihood that Apart from taking a clinical history, all people with a DFU
diagnosis will be valued by them. All aforementioned or gangrene should undergo a complete physical examina-
bedside tests (ABI, TBI, CWD) should be performed by tion, including palpation of the lower limb pulses which can
trained healthcare professionals in a standardised manner help to determine the presence of arterial disease.55 In the
and these tests can be applied by a wide range of practi- systematic review on diagnosis, one low quality study that
tioners, after having received adequate training. From the assessed the diagnostic accuracy of pedal pulse assessment
perspective of middle or high income countries the re- in a population where all participants had a DFU was
sources required to undertake bedside testing are rela- identified.56 Pulse palpation had a PLR of 1.38 and a NLR
tively low compared with other methods of diagnosing 0.75 for PAD in people presenting with a foot ulcer.56 These
PAD such as CDUS, CTA, MRA, and angiography. It is likely likelihood ratios represent a very small ability of the test to
that many people will value the knowledge that their feet identify or exclude disease. Pulse palpation should be seen
need more intensive care to prevent amputation, but this as the first step in a systematic evaluation of the affected
has not been studied in a sufficiently large cohort. Based limb and foot, but when DFU is present further diagnostic
on the uncertainty of the evidence a Conditional Recom- procedures should be performed with non-invasive bedside
mendation was made for additional non-invasive testing in testing techniques as clinical examination is not sufficient to
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 11

exclude PAD. Although of limited value it should not be Rationale

discarded as in the early phase of management other tests Except when required as an emergency to control severe
are sometimes unavailable, or findings may be difficult to infection, all people with diabetes who require foot surgery
interpret. The evidence base is small with low certainty but should have vascular testing consisting of pedal Doppler
as previously discussed this form of testing has low resource waveforms in combination with ABI and toe pressure (TP)
requirements, can be applied on a broad scale by a range of or TBI. Non-emergency invasive procedures, such as elective
practitioners, is feasible, and may increase equity of surgery, may be indicated in people with diabetes without a
healthcare access. This Strong Recommendation is therefore DFU with the intent to address painful foot conditions.
made, based on low certainty of evidence and expert Particularly in those with peripheral neuropathy,64 prophy-
opinion. However, a systematic foot examination for signs of lactic procedures could be considered to address risk factors
ischaemia should be the starting point of a systematic for foot ulceration, such as foot deformity and elevated
evaluation, as failure to diagnose and treat this condition localised plantar pressures. Prior to any surgical procedure
may have dire consequences in many people. When DFU is on the foot in a person with diabetes, PAD status should be
present further diagnostic testing using bedside testing established, and this finding should contribute to determi-
techniques in the first instance should be performed as nation of the suitability of an individual for the procedure.
palpation of foot pulses and clinical examination alone are The decision to perform the elective surgery should be
not sufficient to exclude PAD. made in a shared decision making process that will be
The systematic review identified eight studies56e63 of influenced by balancing the benefit of the operation against
diagnostic accuracy of bedside testing that included partici- the potential harm, such as the risk of poor wound healing
pants with active DFU, with the proportion of the study based on the non-invasive assessments.
population affected ranging from 6.6% to 100%.56,57 One As discussed above, bedside testing generally has mod-
study demonstrated a visual pedal Doppler waveform eval- erate ability to diagnose PAD or to exclude this disease in
uation to be diagnostic (PLR  10), with a moderate ability of people with diabetes mellitus. Any abnormal test result
the test to exclude PAD. In a second study with z 40% of the should be considered indicative of PAD. Therefore, it is
participants having a foot ulcer, the PLR was lower (3.04) and suggested this recommendation will reduce the risk of un-
the NLR similar (0.35).61 In studies in which the majority of diagnosed severe PAD which would potentially negatively
the study population had DFU, an ABI < 0.90 increased the affect post-surgical outcomes and it is likely that people will
pre-test probability of disease by a small amount (PLR 1.69 e value this approach. Feasibility and the impact of these
2.40) with limited ability of the test to exclude disease (NLR tests on resource use are discussed in Recommendation 4.
0.53 e 0.75).56,59,62,63 Similarly, data for the TBI were limited No randomised controlled trials (for ethical reasons) or
and variable with the PLR in both mixed populations (with observational studies of sufficient quality have been per-
and without DFU) and DFU only, ranging from 1.62 (indicating formed on the added value of performing bedside tests
limited ability to diagnose disease) to being diagnostic (PLR  prior to any surgical procedure in the foot. Given the indi-
10) and indicating the test has small to moderate ability to rect evidence discussed above, the major clinical implica-
exclude disease (NLR 0.30 e 0.47).56,59,61,62 tions of missing the diagnosis of PAD and the limited harm
All the aforementioned non-invasive bedside tests (ABI, and additional costs, a Best Practice Statement was made.
TBI, CWD) can be applied by a wide range of practitioners,
in particular in settings where people are treated in sec-
PROGNOSIS
ondary care or specialised outpatient foot clinics. These
tests have low resource requirements relative to other Clinical question
methods of diagnosing PAD such as CDUS and angiography.
In a person with diabetes, suspected PAD, and a foot ulcer
These factors are likely to increase equity in healthcare
or gangrene, which non-invasive bedside tests, alone or in
access and make the tests feasible and acceptable for both
combination, at any time point (including after revascular-
the person having the tests and healthcare providers. Given
isation procedures), predict DFU healing, healing after mi-
the large potential beneficial effect and its impact on sub-
nor amputation, and major amputation?
sequent treatment a Strong Recommendation for this
population has been made, although the limitations of the
Recommendation 6
evidence base are acknowledged.
In a person with diabetes and a foot ulcer or gangrene,
consider performing ankle pressures and ankle brachial
Recommendation 5
index (ABI) measurements to assist in the assessment of
In a person with diabetes without a foot ulcer in whom a non- likelihood of healing and amputation.
emergency invasive foot procedure is being considered, Ankle pressure and ABI are weak predictors of healing. A low
peripheral artery disease should be excluded by performing ankle pressure (e.g., < 50 mmHg) or ABI (e.g., < 0.5) may be
assessment of pedal Doppler waveforms in combination with associated with greater likelihood of impaired healing and
ankle brachial index and toe brachial index. greater likelihood of major amputation.
Grade Certainty of evidence Grade Certainty of evidence
Best Practice Statement Conditional Low

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
12 Robert Fitridge et al.

The predictive capacity of APs and ABI for wound healing was
Recommendation 7
inconsistent in the 15 studies included in the systematic re-
In a person with diabetes and a foot ulcer or gangrene, view.5 Thresholds for AP and ABI which were associated with
consider performing a toe pressure measurement to assess
increased probability of healing could not be identified; how-
likelihood of healing and amputation.
A toe pressure ‡ 30 mmHg increases the pre-test probability ever, a very low ankle pressure (e.g., < 50 mmHg) or ABI (e.g., <
of healing by up to 30% and a value < 30 mmHg increases the 0.5) was associated with a greater likelihood of delayed healing.
pre-test probability of major amputation by approximately According to current guidelines revascularisation should be
20%. considered when such values are measured in people with PAD
Grade Certainty of evidence and an ulcer or gangrene.20 AP and ABI values > 50 mmHg or >
Conditional Low
0.5, respectively, should not be used in isolation to predict
likelihood of ulcer healing given their uncertainty, but detailed
clinical examination and further vascular testing is needed, as
stated in Recommendation 6. Regarding amputation risk, the
probability of major amputation was increased by approxi-
Recommendation 8
mately 45% with an ABI < 0.4 based on one study in people
In a person with diabetes and a foot ulcer or gangrene, if a toe who had undergone transmetatarsal amputation. However, an
pressure cannot be performed, consider performing a ABI threshold < 0.9 was not associated with any probability
transcutaneous oxygen pressure (TcPO2) measurement or a
skin perfusion pressure (SPP) to assess likelihood of healing.
increase.5,67 Thresholds used for AP were highly variable in the
A TcPO2 ‡ 25 mmHg increases the pre-test probability of literature and it was not possible to determine which threshold
healing by up to 45% and value < 25 mmHg increases the pre- was optimal.5 Other research has demonstrated that an
test probability of major amputation by approximately 20%. elevated ABI (> 1.3) is associated with both greater likelihood
An SPP ‡ 40 mmHg increases the pre-test probability of of amputation and worse amputation free survival outcomes
healing by up to 30%.
and therefore should be recognised as a risk factor for poor DFU
Grade Certainty of evidence outcomes. The same observations were made in people
Conditional Low without diabetes, and an elevated ABI is therefore seen as a
marker for more severe cardiovascular disease with an elevated
risk of amputation.68,69
Rationale TP and TBI can assess blood flow distal to the forefoot and
The presence of PAD constitutes a substantially increased risk of in toes, where most DFUs occur.70 Based on 10 studies of low
failure to heal and major lower limb amputation for people with quality it was found that with TP  30 mmHg the pre-test
a diabetes related foot ulcer or gangrene. Bedside testing results probability of healing was increased by up to 30%.71
are an integral component of determining the severity of Regarding major amputation, a value < 30 mmHg increases
ischaemia and, to that end, to determine the need for, and ur- the probability of major amputation by approximately 20%,
gency of, further investigations. Non-invasive bedside tests which suggests a (somewhat) lower predictive capacity
including AP, ABI, and TP should be performed in a person with a compared with the ABI. In the three studies identified, there
DFU or gangrene to guide further management as they can help was inconsistent and insufficient evidence for the use of the
to predict the chance of healing and or major amputation.TcPO2 TBI to predict either healing or major amputation.
and skin perfusion pressure (SPP) give additional information on TcPO2 and SPP are additional tests that have the advantage
healing potential and are useful for measuring perfusion of measuring perfusion at tissue level and therefore reflect
following forefoot amputations when TP are no longer possible. both macrovascular and microvascular function. In the sys-
However, in the authors’ opinion these are secondary tests due tematic review the majority of available studies (n ¼ 7) which
to greater expense and less availability of the equipment and were of low quality, reported that TcPO2 can be used to predict
the time and expertise required to apply them. the likelihood of DFU healing,71e80 although there is variability
Assessment of the pedal arterial Doppler waveforms com- in the thresholds used. With a TcPO2  25 mmHg the pre-test
bined with measurement of the AP and subsequent calculation probability of healing is increased by up to 45%, which was
of the ABI, are usually the first steps in the assessment of PAD. higher than reported for the other tests in the included studies.
Although relevant for its diagnosis, as discussed in the Ratio- Regarding amputation, a value < 25 mmHg increases the
nales of Recommendations 1 and 2, it was not possible to probability of major amputation by approximately 20%, a
identify sufficient data on the capacity for Doppler arterial predictive value that seems lower than that of the ABI when
waveform analysis to predict wound healing in populations the different studies were compared. An SPP ( 40 mmHg)
with DFU.5 Two low quality studies were identified which was shown to increase the pre-test probability of healing by up
concluded that abnormal or absent Doppler waveforms were to 30% in one study of low quality.81 There are insufficient data
associated with a small (15%) increase in the likelihood of investigating the relationship between SPP and amputation
major amputation,65,66 further limiting its use. Similarly, there outcomes to formulate a recommendation.
are currently insufficient data to support the use of TBI to In summary, when comparing different studies, the ABI
predict healing or amputation outcomes; however, TP (as a seemed to have the best predictive capacity for major
component of TBI) has been more widely investigated and is amputation, while the TP and TcPO2 seemed to have a
therefore included in the recommendation. better predictive capacity for wound healing. It was
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 13

noteworthy that there was insufficient evidence for the use have assumed that microvascular disease is present in a
of the TBI to predict either healing or amputation out- high proportion of people with DFU and that it is a major
comes. The number of prospective studies and the number cause of delayed wound healing, often despite a lack of
of participants included in the aforementioned studies were thorough investigation of large vessel arterial disease. As
relatively low, the populations studied differed, and results discussed elsewhere in this guideline, people with diabetes
of the tests performed were frequently not blinded. and a DFU frequently have distal, lower leg obstructive
Moreover, comparison of studies was hampered by the fact atherosclerotic disease, often with involvement of the pedal
that different studies used different thresholds for disease arteries, which due to their smaller size can be difficult to
and thus combining data for analysis was not possible. image. However, advances in imaging and technology have
When bedside testing is not performed the risks of a poor shown that tibial and pedal arteries are potentially treatable
clinical outcome or unnecessary, more costly, investigations by endovascular and open surgical techniques.
are large. As discussed earlier, most bedside tests are of low The term microvascular disease describes abnormalities
burden to both the person and the healthcare system, affecting the arteriolar, capillary and venular vessels. Several
although training and expertise are necessary. If these tests are studies have reported microvascular abnormalities in the skin
not performed, the clinician must rely only on clinical judge- and subcutaneous tissues in people with diabetes. These
ment and on imaging investigations. Although imaging will abnormalities can be structural, i.e. occlusive disease and
provide details of the arterial anatomy, the non-invasive alterations in the blood vessel wall, and functional, such as
bedside tests will inform the clinician about the perfusion in impaired vasodilatory responses to endogenous or noxious
the foot. However, absolute perfusion thresholds applicable stimuli.82 However, in the systematic review on this topic it
for all people cannot be provided as the outcome of the DFU is was not possible to identify studies of sufficient quality
determined not only by the degree of ischaemia. Other factors showing that such abnormalities contribute to impaired
such as infection, extent of tissue loss, and ulcer depth, can wound healing (Supplementary material). One prospective
have a major effect on healing potential and amputation risk, study did report that microvascular changes observed in skin
as discussed below. For this reason and the uncertainty of the biopsies in the feet in people with diabetes and neuro-
evidence, a Conditional Recommendation for use of AP, ABI, ischaemia were associated with poorer wound healing after
and TP to predict the likelihood of healing and amputation was revascularisation.83 However, both these microvascular
made. changes and poorer wound healing could be due to tissue
TcPO2 and SPP tests require more expensive equipment and damage caused by ischaemia and not by pre-existing diabetes
greater expertise for application than other bedside testing, related micro-angiopathy. If perfusion of the foot ulcer is
which may be a barrier for centres in low or middle income adequate but the ulcer fails to heal, other causes of poor
countries. Although healthcare expenditures may increase wound healing should be sought and treated, such as infec-
with each of these measurements, incorrect assessment of the tion, insufficient protection from biomechanical stress,
severity of PAD can result in inadequate treatment and poorer oedema, poor glycaemic control, poor nutritional state, and
outcomes with ultimately an increase in costs. Importantly, all underlying co-morbidities.43 Based on the lack of studies
the aforementioned bedside tests have varying capacity to showing that diabetes related micro-angiopathy contributes
predict likelihood of healing and of amputation, as summarised to poor wound healing in DFU and the potential harm if this is
in the systematic review.6 Based on current evidence no test assumed, a Conditional Recommendation based on low cer-
has convincingly been shown to perform better than other tainty of evidence was made.
tests as a prognostic indicator of both healing and amputation.
In the opinion of the Writing Committee multiple tests should Recommendation 10
be used. Given the limited available evidence on TcPO2 and In a person with diabetes, peripheral artery disease, and a
SPP and their higher costs, a Conditional Recommendation on foot ulcer or gangrene, consider using the Wound/
these two tests was made. Ischaemia/foot Infection (WIfI) classification system to
estimate healing likelihood and amputation risk.
Recommendation 9 Grade Certainty of evidence
In a person with diabetes and a foot ulcer or gangrene, it is Conditional Low
suggested that the presence of peripheral artery disease and
other causes of poor healing should always be assessed.
Diabetes related micro-angiopathy should not be considered Rationale
the primary cause of foot ulceration, gangrene, or poor The Wound, Ischaemia and Foot infection (WIfI) classification
wound healing without excluding other causes.
system was developed to guide the clinician in estimating the
Grade Certainty of evidence risk of amputation and potential benefit of revascularisation in
Conditional Low people with a foot ulcer or gangrene, and is recommended by
the Global Vascular Guideline for limb staging (relating to
severity of limb threat) in people with chronic limb threatening
Rationale ischaemia (CLTI).20 This system was developed by an inter-
The definition of microvascular disease in DFU and its role disciplinary panel of experts and stages the limb based on the
in wound healing are not well understood. Many clinicians presence of, and severity of, the foot wound, ischaemia, and
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
14 Robert Fitridge et al.

infection. A Delphi consensus process was used to allocate

Table 1. Wound Ischaemia foot Infection Classification System:
these combinations into four clinical stages based on very low Wound clinical category adapted from Mills et al. (reference 84)
(stage 1), low (stage 2), moderate (stage 3), and high (stage 4)
predicted one year risk of major amputation. Consistent with Grade Clinical description
all other commonly used limb staging systems, the individual’s 0 Ischaemic rest pain; without ulcer or gangrene
co-morbidities which are likely to influence wound healing and 1 Minor tissue loss: small shallow ulceration on foot
amputation risk are not incorporated into WIfI. A second or distal leg. No gangrene.
distinct aspect of the WIfI system is the predicted likelihood of Salvageable with simple skin coverage or  2 toe
benefit from revascularisation.84 amputations
2 Major tissue loss: deeper ulceration(s) with exposed
A recent systematic review concluded that in people bone, joint or tendon not involving calcaneus.
undergoing a revascularisation procedure, the likelihood of Gangrenous changes limited to digits.
an amputation after one year increases with higher WIfI Salvageable with extensive forefoot surgery
stages. The estimated one year major amputation rates 3 Extensive ulcer or gangrene involving forefoot or
from four studies comprising 569 participants were 0%, 8% midfoot; full thickness heel ulcer  calcaneal
involvement.
(95% CI 3 e 21%), 11% (95% CI 6 e 18%), and 38% (95% CI Salvageable with complex foot reconstruction and/
21 e 58%), for WIfI clinical stages 1e4, respectively.85 For or complex wound management
the population of people with a DFU, the WIfI system was
evaluated in the IWGDF systematic review on classification
systems, that is published in parallel to this guideline. In
summary, in people with diabetes, PAD, and a foot ulcer, Recommendation 11
this systematic review identified seven studies, with
In a person with diabetes, peripheral artery disease, and a
low certainty of evidence, demonstrating that a high WIfI foot ulcer or gangrene who is being considered for
limb clinical stage is associated with longer time to revascularisation, evaluate the entire lower extremity
healing and increased likelihood of non-healing at six and arterial circulation (from aorta to foot) with detailed
12 months.86e92 Higher WIfI clinical stages are also associ- visualisation of the below knee and pedal arteries.
ated with increased likelihood of major amputation, with one Grade Certainty of evidence
study reporting an amputation rate of 64% for stage 4.93
Best Practice Statement
Similarly, higher WIfI clinical stages have been linked to
high rates of minor amputation and lower rates of amputa-
tion free survival at 12 months.88,89,92,94e99 For prediction of Rationale
revascularisation benefit there are few data available and As per Recommendations 1 e 4, clinical examination and
inadequate evidence to determine whether WIfI revascular- bedside testing should be the first line testing undertaken to
isation benefit staging predicts healing or amputation out- diagnose the presence of PAD. When revascularisation is being
comes in people undergoing revascularisation. considered further anatomical information on the arteries of
The WIfI tool (Tables 1e5) has demonstrated predictive the lower limb should be obtained to assess the presence,
capacity for the key outcomes of wound healing and ampu- severity, and distribution of arterial stenoses or occlusions. In
tation in people with DFU.88,89,92,94e99 It uses clinical grading of this process, adequate imaging of the tibial and pedal vessels is
infection and wound characteristics in combination with non- of critical importance, particularly in planning intervention in
invasive bedside testing to determine the severity of ischaemia people with diabetes and a foot ulcer.20 Modalities that can be
and it has wide availability, also as an online tool (https://apps. used to obtain anatomical information include CDUS, CTA,
apple.com/us/app/svs-ipg/id1014644425). Moreover, it can MRA, or DSA (including anteroposterior and lateral views of the
be used by a wide range of practitioners making its application foot). The Writing Committee considered that each of the im-
in clinical practice feasible, its costs are relatively limited, and it aging techniques have their advantages and disadvantages, and
is expected to be acceptable to practitioners as well as being of their use will depend heavily on the availability of equipment
value to people receiving the care. It is likely to stimulate a and local expertise, preferences of the individual clinician, and
standardised access to a form of vascular assessment, which is associated costs. For these reasons a Best Practice Statement
also relevant for low income countries where invasive testing was formulated. Regarding their use in people with diabetes,
may not be widely available. Due to the observational and
often retrospective nature of most of the current evidence, this Table 2. Wound Ischaemia foot Infection Classification System:
recommendation was made Conditional. Ischaemia category adapted from Mills et al. (reference 84)

TREATMENT Grade ABI Ankle SP e mmHg TP, TcPO2 e mmHg

0 0.8 >100 60
Clinical question 1 0.6e0.79 70e100 40e59
In which persons with diabetes, PAD, and a foot ulcer or 2 0.40e0.59 50e69 30e39
3 <0.40 <50 <30
gangrene using clinical findings, perfusion test findings, and
ABI ¼ ankle brachial index; SP ¼ systolic pressure; TP ¼ toe pressure;
or classification systems, should revascularisation be
TcPO2 ¼ transcutaneous oxygen pressure.
considered?
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 15

Table 3. Wound Ischaemia foot Infection Classification System: foot Infection category adapted from Mills et al. (reference 84)

Grade Clinical description IDSA IWGDF

Class
0 Wound without purulence or manifestations of infection Uninfected 1
1 > 2 manifestations of infection, erythema (< 2 cm), pain or tenderness, warmth, induration or purulent Mild 2
discharge
2 Local infection in a patient who is systemically stable as described above with erythema > 2cm, or Moderate 3
involving subcutaneous structures e.g., abscess, osteomyelitis, septic arthritis or fasciitis
3 Infection in patient with systemic or metabolic toxicity (systematic inflammatory response Severe 4
syndrome/ sepsis)
IDSA ¼ The Infectious Diseases Society of America; IWGDF ¼ International Working Group on the Diabetic Foot.

the utility of some these techniques, such as CDUS and CTA, salvage rate was around 50% at one year.73,100 Analysis of the
can be affected by (severe) MAC, which is frequently present in evidence for revascularisation suggests that revascularisation
the smaller arteries of the leg in people with DFU. MRA images in appropriately selected people with diabetes and haemo-
are incapable of defining the extent of calcification which may dynamically significant PAD, can improve perfusion, expedite
be important when planning revascularisation.20 Finally, as wound healing, and reduce major limb amputations.6 After a
stated in the GVG, catheter DSA, represents the gold standard revascularisation procedure, most studies report limb salvage
imaging technique, especially for the below knee and foot ar- rates of 80 e 85% and ulcer healing in > 60% at 12
teries.20 In many centres DSA is typically used when MRA or months.101 On the other hand, performing a revascularisa-
CTA are not available, fail to adequately define the arterial tion is not without risks. As summarised in the systematic
anatomy, or when an endovascular intervention is planned. review performed by the IWGDF in 2019,101 the peri-
Arterial imaging should allow complete anatomical staging from operative or 30 day mortality rate was around 2% in peo-
aorta to foot using, for example, TASC for aorto-iliac disease and ple with diabetes undergoing either endovascular or surgical
the Global Anatomic Staging System (GLASS), described in the revascularisation.101 The highest risk group includes people
GVG, for infrainguinal and pedal disease.20 with end stage renal disease, who have a 5% peri-operative
mortality rate, 40% one year mortality rate, and one year
Recommendation 12 limb salvage rate of around 70%.101
In a person with diabetes, peripheral artery disease, a foot
People with signs of ischaemia, e.g., as defined by WIfI
ulcer, and clinical findings of ischaemia, a revascularisation and the GVG; absent pulses and monophasic or absent
procedure should be considered. Findings of ischaemia pedal Doppler waveforms, ankle pressure < 100 mmHg or
include absent pulses, monophasic or absent pedal Doppler toe pressure < 60 mmHg, are very likely to have significant
waveforms, ankle pressure < 100 mmHg or toe pressure < 60 PAD that could impact wound healing potential and
mmHg. Consult a vascular specialist unless major amputation
is considered medically urgent.
amputation risk.20,84 The certainty of evidence in the sys-
tematic review on the effects of revascularisation on wound
Grade Certainty of evidence
healing and amputation risk was judged to be very low, as
Best Practice Statement many important factors that can affect outcomes were not
reported, such as the availability of vein conduit, wound
care, offloading, and sufficient anatomical details about the
Rationale extent and severity of the lesions treated. Factors that in-
The natural history of people with diabetes, PAD, and a DFU fluence the decision to revascularise include the degree of
or gangrene remains poorly defined, but in two studies limb threat (e.g., WIfI classification), the amount of tissue
reporting the outcomes of participants with diabetes and loss, presence of infection, co-morbidities, feasibility of the
limb ischaemia who were not revascularised, the limb different revascularisation options, and their risks.

Table 4. Wound Ischaemia foot Infection Classification System: estimated risk of amputation at one year adapted from Mills et al.
(reference 84)
Ischaemia e 0 Ischaemia e 1 Ischaemia e 2 Ischaemia e 3
W-0 VL VL L M VL L M H L L M H L M M H
W-1 VL VL L M VL L M H L M H H M M H H
W-2 L L M H M M H H M H H H H H H H
W-3 M M H H H H H H H H H H H H H H
fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3
VL ¼ Very Low ¼ Class or Clinical Stage 1
L ¼ Low ¼ Class or Clinical Stage 2
M ¼ Moderate ¼ Class or Clinical Stage 3
H ¼ High ¼ Class or Clinical Stage 4

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
16 Robert Fitridge et al.

Table 5. Wound Ischaemia foot Infection Classification System: estimated likelihood of benefit of or requirement for
revascularisation adapted from Mills et al. (reference 84)
Ischaemia e 0 Ischaemia e 1 Ischaemia e 2 Ischaemia e 3
W-0 VL VL VL VL VL L L M L L M M M H H H
W-1 VL VL VL VL L M M M M H H H H H H H
W-2 VL VL VL VL M M H H H H H H H H H H
W-3 VL VL VL VL M M H H H H H H H H H H
fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3 fI-0 fI-1 fI-2 fI-3
VL ¼ Very Low ¼ Class or Clinical Stage 1
L ¼ Low ¼ Class or Clinical Stage 2
M ¼ Moderate ¼ Class or Clinical Stage 3
H ¼ High ¼ Class or Clinical Stage 4

As discussed in other parts of the IWGDF guidelines, for revascularisation, unless contraindicated or technically not
restoration of perfusion in the foot is only part of the possible. There is retrospective evidence demonstrating that a
treatment required to optimise wound healing and to delay in revascularisation of more than two weeks in people
prevent or limit tissue loss, which should be provided by a with diabetes results in increased risk of limb loss.102 This is
multidisciplinary team.43 Any revascularisation procedure supported by observational research demonstrating that a
should be part of a comprehensive care plan that addresses shorter time to revascularisation (< 8 weeks) is associated
other important issues including: prompt treatment of with a higher probability of DFU healing and lower likelihood
concurrent infection, regular wound debridement, biome- of limb loss.74 As shorter time to revascularisation was
chanical offloading, control of blood glucose, assessment associated with higher probability of DFU healing and lower
and improvement of nutritional status, as well as treatment likelihood of limb loss, a Best Practice Statement supporting
of oedema and co-morbidities.43 The decision to perform a urgent referral for vascular consultation in people with DFU
revascularisation procedure and which procedure is and evidence of severe ischaemia was made (Fig. 1).
preferred depends therefore on several factors and in each
individual the balance should be made between expected Recommendation 14
benefits, potential risks, harms and costs, in a shared de- In a person with diabetes, peripheral artery disease, and a
cision making process. For these reasons a Best Practice foot ulcer with infection or gangrene involving any portion of
Recommendation was made. The care of persons with a the foot, urgently consult a vascular specialist in order to
DFU is frequently managed by healthcare professionals who determine the timing of a drainage procedure and a
are not specifically trained in the treatment of PAD. Care for revascularisation procedure.
people with PAD is differently organised in many countries, Grade Certainty of evidence
with different medical disciplines involved, such as vascular Best Practice Statement
surgeons, angiologists, interventional radiologists, nephrol-
ogists, cardiac surgeons, and cardiologists. For this reason,
the term vascular specialist consultation is used in the Rationale
recommendation, but whatever the organisation of care all
people with diabetes and PAD should have access to both In the presence of PAD and infection or gangrene, an ur-
bypass surgery and endovascular procedures. gent revascularisation should be considered. In the pro-
spective Eurodiale study, participants with the
Recommendation 13
combination of a foot infection and PAD had a one year
major amputation rate as high as 44%.103 In addition,
In a person with diabetes, peripheral artery disease, a foot
participants with higher WIfI infection grade had higher
ulcer, and severe ischaemia i.e., an ankle brachial index
< 0.4, ankle pressure < 50 mmHg, toe pressure < 30 mmHg or risk of amputation in several observational studies, as
transcutaneous oxygen pressure < 30 mmHg or monophasic summarised in the IWGDF systematic review on Classifi-
or absent pedal Doppler waveforms, urgently consult a cation Systems (https://onlinelibrary.wiley.com/doi/10.
vascular specialist regarding possible revascularisation. 1002/dmrr.3645).38 Delay in treatment can lead to rapid
Grade Certainty of evidence tissue destruction and life threatening sepsis as described in
Best Practice Statement
the IWGDF/IDSA Guidelines on Management of Diabetic
Foot Infections.104 In a person with a foot abscess or infection of
a deep foot compartment that needs immediate drainage, or
where there is gangrene that must be removed to control the
Rationale infection, immediate surgery should be considered first.104 This
Severe ischaemia is defined in the GVG as an ABI < 0.4, AP should be accompanied by broad spectrum antibiotic therapy,
pressure < 50 mmHg, TP < 30 mmHg or TcPO2 < 30 mmHg which is subsequently tailored according to tissue culture re-
or monophasic or absent pedal Doppler waveforms.20,84 Such sults, as “time is tissue” in these people. Once the sepsis is
perfusion deficits are, as also stated in the GVG, an indication controlled and the person is stabilised, evaluation of the arterial
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 17

Person with diabetes and an ulcer or gangrene

Wound care and offloading as Assess for presence of infection and

Palpate pulses and examine for signs of ischaemia
recommended by IWGDF manage as recommended by IWGDF

Evaluate pedal Doppler waveforms, perform ABI and TBI

to diagnose or exclude PAD

Use Wifi to stratify healing likelihood and amputation risk

Absent pulses, monophasic or absent ABI 0.90–1.3, TBI ≥ 0.70, triphasic

pedal Doppler waveforms or ankle PAD, ulcer with infection or biphasic pedal Doppler waveforms,
pressure < 100 mm Hg or or gangrene persist with wound care and treatment
TP < 60 mm Hg of infection as needed

ABI < 0.4, ankle pressure < 50 mm Hg, Consult vascular specialist Urgent consultation by Re-assess perfusion if there is lack of
TP < 30 mm Hg or TcPO2 < 30 mm Hg unless urgent amputation vascular specialist healing progress at 4 weeks
or monophasic or absent pedal Doppler indicated
waveforms

Urgent revascularisation procedure should

be considered, consult vascular specialist

Figure 1. Assessment and management pathway for a person with diabetes, peripheral artery disease, and a foot ulcer with findings of
ischaemia, infection, or gangrene. Yellow ¼ Conditional Recommendation; green ¼ Strong Recommendation; gray ¼ Best Practice
Recommendation; ABI ¼ ankle brachial index; IWGDF ¼ International Working Group on the Diabetic Foot; TBI ¼ toe brachial index; TP ¼
toe pressure; PAD ¼ peripheral artery disease; WIfI ¼ Wound Ischaemia foot Infection classification system

tree should lead to consideration for prompt revascularisation depth, elevated foot pressures at the wound site, and inad-
(i.e., within a few days) in people with substantial perfusion equate wound care. A number of studies have demonstrated
deficits. Once blood flow is improved and infection is that a reduction in percentage of wound area of more than
controlled, a definitive operation may be required to create a 50% by four weeks after presentation is predictive of healing
functional foot, which may require soft tissue and bone at 12 weeks.106e109 This has been shown to be the case
reconstruction.105 Due to the risk of amputation in this clinical independent of the ulcer size at baseline and supports review
scenario, the likelihood that the person will value avoidance of of treatment protocols where adequate wound reduction is
amputation, and the need for appropriate prioritisation of not being achieved in the four week timeframe. Presence of
intervention strategies to achieve this, the Writing Committee suspected CLTI or a DFU that is failing to adequately heal
formulated a Best Practice Statement. despite best practice care requires prompt consultation with
a vascular specialist and assessment of whether a revascu-
Recommendation 15 larisation procedure is indicated. There is no direct evidence
In a person with diabetes and a foot ulcer, when the wound
supporting the recommendation which is a pragmatic
deteriorates or fails to significantly improve (e.g., a less than statement based on indirect evidence and expert opinion.
50% reduction in wound area within four weeks) despite Given the risk of poor outcomes when PAD is left untreated
appropriate infection and glucose control, wound care, and in a person with a poorly healing ulcer, a Best Practice
offloading, reassess the vascular status and consult with a Statement has been made.
vascular specialist regarding possible revascularisation.
Grade Certainty of evidence Recommendation 16
Best Practice Statement In a person with diabetes, peripheral artery disease, and
a foot ulcer or gangrene, avoid revascularisation when the
riskebenefit ratio for the probability of success of the
intervention is clearly unfavourable.
Rationale
Grade Certainty of evidence
Multiple factors may contribute to delayed or non-healing
of DFU, including presence of infection, wound size and Best Practice Statement

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
18 Robert Fitridge et al.

Rationale Rationale
Revascularisation should not be performed if there is no Once the decision to revascularise has been made, the next
realistic chance of wound healing, when major amputation is decision is whether an endovascular, an open (i.e., bypass
inevitable, a functional foot is unlikely to be achieved, or when or endarterectomy) procedure, or a combination of both
life expectancy is short and there is unlikely to be benefit to the (i.e., hybrid procedure) should be performed. Recommen-
person. The Writing Committee considered that in such per- dation 18 highlights the complementary role of open and
sons any revascularisation procedure is unlikely to be of endovascular techniques in contemporary vascular practice.
benefit to the person and may cause harm. Many affected In particular, endovascular techniques have largely replaced
individuals pose high peri-procedural risk because of comor- open surgery in the management of aorto-iliac disease and
bidities. In particular, the following people may not be suitable also allow treatment of foot and pedal arch disease.
for revascularisation: those who are very frail, have short life The majority of studies identified in the systematic re-
expectancy, have poor functional status, are bed bound, and or view on endovascular and bypass surgical outcomes were
have a large area of tissue destruction that renders the foot observational and retrospective case series, with a high risk
functionally unsalvageable and those who cannot realistically of bias.7 The BEST CLI trial was a large randomised clinical
be expected to mobilise following revascularisation. There are trial with low risk of bias comparing an endovascular first
occasional situations where an arterial inflow procedure is with a surgical first approach. People with CLTI who were
performed to improve the likelihood of healing of a major limb deemed appropriate for revascularisation for infrainguinal
amputation (below or above knee). arterial occlusive disease were included.111 The primary
There is evidence from several observational studies of a outcome was above ankle amputation of the index limb or a
50% healing rate for ischaemic DFU in people with diabetes major re-intervention in the index limb (new bypass, vein
unsuitable for revascularisation and this should also be graft interposition revision, thrombectomy or thrombolysis)
considered in determining choice of care.74,100 The decision to or death. It was designed in two parallel cohort trials:
proceed to primary amputation, or to adopt a palliative Cohort 1 people who had an adequate single segment great
approach, should be made in conjunction with the person and saphenous vein (GSV) available for use as a bypass conduit,
the multidisciplinary team110 including a vascular specialist and Cohort 2 people without an adequate single segment
unless an emergency procedure is indicated as discussed GSV who required an alternate conduit. Treatment with a
earlier. The Writing Committee considered that in these cir- GSV bypass first approach was superior to endovascular
cumstances where healing is improbable a person is unlikely to therapy first for the primary outcome (hazard ratio [HR],
value the outcomes from revascularisation over no revascu- 0.68; 95% confidence interval [CI] 0.59 e 0.79; p < .001). In
larisation. Similarly in such circumstances the benefit of
Cohort 2 the primary outcomes were similar between the
revascularisation will not outweigh the potential harms.
two groups. Subgroup analysis of people in Cohort 1 fav-
Clinical question oured surgery in people with diabetes (HR 0.72; CI 0.61 e
In people with diabetes, PAD, and either a foot ulcer or 0.86) with benefit comparable with those without diabetes
gangrene, how does endovascular revascularisation (HR 0.57; CI 0.41 e 0.78). At the time of writing this
compare with open or hybrid revascularisation? guideline, further results of this study have not been pub-
lished. Of note, whole group data for Cohort 1 demon-
strated a higher rate of major amputation in those
Recommendation 17 undergoing an endovascular procedure compared with
those having surgery (Surgery: 74/709 [10.4%] Endovas-
In a person with diabetes, peripheral artery disease, and a
foot ulcer or gangrene who has an adequate single segment
cular: 106/711 [14.9%]). Further subanalysis may demon-
saphenous vein in whom infrainguinal revascularisation is strate this is relevant to those with diabetes and therefore
indicated and who is suitable for either approach, consider this may affect an individual’s preference for intervention.
bypass in preference to endovascular therapy. From the perspective of the person receiving treatment, the
Grade Certainty of evidence difference in length of hospital stay should be taken into
Conditional Moderate
account, which in the systematic review was longer in the
bypass publications than in endovascular publications. In
addition, people might prefer to have an endovascular
Recommendation 18 approach given the more invasive approach of bypass
A person with diabetes, peripheral artery disease (PAD) and a surgery.
foot ulcer or gangrene, should be treated in a centre with Considering costs, there are probably no major differ-
expertise in, or rapid access to, endovascular and surgical ences except the length of hospital stay; however, this is yet
bypass revascularisation. In this setting, consider making to be determined and may be an additional outcome of the
treatment decisions based on the risk to and preference of the
individual, limb threat severity, anatomical distribution of
BEST-CLI study. Subsequent analyses are also awaited to
PAD, and the availability of autogenous vein. shed more light on the anatomical patterns and extent of
disease treated, as well as which patterns of disease were
Grade Certainty of evidence
not well represented or excluded. As BEST-CLI is currently
Best Practice Statement the only randomised controlled trial (RCT) in this area, the
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 19

certainty of the evidence for the recommendation was

Recommendation 19
moderate. Given the important differences in outcomes in
the BEST-CLI trial it is recommended to consider bypass In a person with diabetes, peripheral artery disease, and a
foot ulcer or gangrene, revascularisation procedures should
surgery as the first option in people with a suitable
aim to restore in line blood flow to at least one of the foot
saphenous vein. It is acknowledged that this recommen- arteries.
dation may lead to some major changes in the policy of the
Grade Certainty of evidence
many centres, which currently have an endovascular first
approach for everyone. Best Practice Statement
The recommendation may not be feasible in the short
term in all countries due to the lack of equipment and
Rationale
expertise. Finally, it should be noted that in the BEST-CLI
study, endovascular procedures could be performed in the In people with diabetes and a foot ulcer or gangrene
iliac and common femoral artery to ensure optimal inflow in whom revascularisation is required, optimising
into the bypass, emphasising that a centre treating PAD in blood flow to the foot is important to maximise the chance
people with a DFU should have the expertise to perform of healing the foot and avoiding amputation. Incomplete
both endovascular and bypass procedures. In addition, in revascularisation (including treating inflow disease when
some centres the immediate availability of an endovascular distal disease is present or bypassing into blind segment
approach might be a reason to opt for this treatment when arteries with no runoff), can result in delayed or non-wound
an urgent revascularisation is needed or when the surgical healing and a substantial risk of amputation.
risk is deemed too high. For these reasons and the mod- Bypass surgery is ideally performed to an outflow
erate certainty of the evidence a Conditional Recommen- vessel that runs into the foot. However, bypasses per-
dation was made. formed to the peroneal artery (which rely on collaterali-
In people with diabetes in whom a revascularisation is sation to the foot) are most effective when there is good
considered but who do not have a suitable single segment collateralisation to the foot and a patent pedal arch is
GSV for bypass surgery, the results in BEST-CLI were similar present.99 Pedal arch patency also seems to be associated
for endovascular and surgical bypass. This statement is in with improved wound healing and reduced risk of major
line with the results of the systematic review, in which the amputation.113
non-randomised and observational studies showed that the
evidence was inadequate to establish whether an endo-
vascular, open, or hybrid revascularisation technique is su- Recommendation 20
perior. Each of these techniques has its advantages and In a person with diabetes, peripheral artery disease, and a
disadvantages. A successful distal venous bypass can result foot ulcer or gangrene undergoing an endovascular
in a marked increase of blood flow to the foot, but general, procedure, consider targeting the artery on angiography that
spinal, or epidural anaesthesia is usually necessary and a supplies the anatomical region of the ulcer, when possible or
practical.
suitable vein, as a bypass conduit, should be present, as in
the BEST-CLI trial. An endovascular procedure has several Grade Certainty of evidence
logistical advantages, but sometimes, very complex in- Conditional Very low
terventions are necessary to obtain adequate blood flow in
the foot and a failed endovascular intervention may lead to
worse outcomes when an open procedure is performed Rationale
subsequently.112 Over the past few decades, there have Angiosomes are three dimensional regions of tissue and
been significant advances in endovascular techniques; skin supplied by a source artery. The six angiosomes of the
however, parallel to this, there have been improvements in foot and ankle are supplied by the posterior tibial artery
anaesthesia and peri-operative care that have helped (n ¼ 3), peroneal artery (n ¼ 2), and anterior tibial artery
improve surgical outcomes. As there is no one size fits all (n ¼ 1) (Fig. 3). Communications between angiosomes
approach to treatment for people with diabetes, PAD, and include direct arterial to arterial connections, as well as
foot ulceration or gangrene, it is important that a treating choke vessels which link adjacent angiosomes.113e115 The
centre has the expertise and facilities to provide a range of effect or influence of angiosome based revascularisation on
treatment options with availability of both endovascular wound healing and prevention of amputation (major and
and open techniques. It is recommended that for each minor) in the management of diabetes related foot com-
person requiring lower limb revascularisation, all revascu- plications remains controversial.
larisation techniques should be considered (Fig. 2). Direct revascularisation involves revascularisation of the
tibial artery supplying the angiosome in which the tissue
Clinical question loss has occurred. The alternative to this is indirect revas-
In people with diabetes, PAD, and either a foot ulcer or cularisation where the tibial artery treated is the artery in
gangrene, how does direct angiosome revascularisation which successful in line flow to the foot is most likely to be
compare with indirect angiosome revascularisation? achieved by endovascular techniques or is deemed the best

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
20 Robert Fitridge et al.

Person with diabetes, PAD and an ulcer, gangrene

in whom revascularisation is indicated

Image arterial system from aorta to pedal arch using;

Arterial colour duplex ultrasound
CT Angiography
MR Angiography
or DS Angiography

Assess GSV for suitability for bypass if open bypass Patient deemed unfit for bypass or arterial
or endovascular intervention likely indicated lesion considered suitable for straightforward
endovascular procedure

Patient suitable for bypass or endovascular procedure DS angiography ± intervention

Ideally target artery supplying angiosome

Single segment GSV suitable associated with ulcer or gangrene
Suitable single segment GSV for bypass not available
Consider bypass Endovascular procedure or
bypass

Figure 2. Approach to vascular intervention for a person with diabetes and a foot ulcer or gangrene. Yellow ¼
Conditional Recommendation; gray ¼ Best Practice Recommendation; PAD ¼ peripheral artery disease; CT ¼
computed tomography; GSV ¼ great saphenous vein; MR ¼ magnetic resonance; DS ¼ digital subtraction.

tibial outflow vessel for anastomosis in bypass surgery but (extent of tissue loss, severity of ischaemia, presence of
does not directly supply the affected area of tissue loss. The infection). Comparison of primary outcomes (healing and
systematic review found that open vascular reconstruction amputation) or adverse events is therefore problematic.
procedures were equally effective whether direct or indirect Based on the available data it appears direct revascular-
revascularisation to the affected foot angiosome was isation may have improved outcomes and therefore it was
performed.7 considered that this procedure is likely to be preferred by
In addition, healing and amputation outcomes for direct people receiving treatment to improve healing and pre-
and indirect endovascular revascularisation show that if vent amputation. However, the Writing Committee
direct revascularisation is possible, DFU healing time and considered there is likely to be important variability in
major amputation may be reduced compared with indirect patient values due to the lack of clear benefit of one
revascularisation. There is inadequate evidence to deter- approach over the other.
mine whether direct revascularisation is superior to indirect Factors such as the severity of ischaemia and tissue loss
revascularisation to prevent minor amputation.116 Indirect (e.g., WIfI staging) and patient suitability for the procedure
revascularisation with collaterals was associated with
wound healing and limb salvage outcomes which were
similar to direct revascularisation outcomes and notably Medial plantar
Anterior tibial artery
better than the indirect revascularisation without collateral artery
cohorts.117e121
The majority of studies included in the systematic re-
view used endovascular procedures with data probably Lateral plantar
favouring direct revascularisation. For bypass procedures Posterior tibial artery

there was little difference in healing and amputation artery

Peroneal artery
outcomes at 12 months between direct and indirect
revascularisation.121e124 These studies had a high risk of Anterior tibial artery
bias, lacked randomisation (and it is unlikely that this will Posterior tibial
ever be possible), and were mostly retrospective. Baseline artery
Peroneal artery
variables such as wound and foot staging (e.g., by WIfI)
and extent of tissue loss were reported infrequently. Dorsalis pedis artery
Heterogeneity of the included studies was found to be
high, preventing meta-analysis of data. This is likely to be
Figure 3. Angiosome distribution in the lower leg and foot.
due to high variability in participants and wound stage

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 21

and presence of comorbidities, as well as the availability of based on indirect evidence and expert opinion has been
expertise and costs of the procedures (which may vary made.
between locations and countries) drives decision making in
relation to the type of procedure considered appropriate Recommendation 22
with these factors also impacting. Several studies have A person with diabetes, peripheral artery disease, and either
noted that only a minority of foot and ankle wounds in their a foot ulcer or gangrene should be treated by a
series corresponded to one angiosome. Kret et al.125 found multidisciplinary team as part of a comprehensive care plan.
that only 36% of wounds in their series corresponded to a Grade Certainty of evidence
single distinct angiosome. Similarly, Aerden et al.126 found it
Best Practice Statement
difficult to allocate people to direct revascularisation versus
indirect revascularisation due to the presence of multiple
wounds and large wounds that had more than one angio-
some supplying them. In such cases it is the opinion of the Rationale
Writing Committee that the best quality artery should As discussed in several parts of this guideline and in other
preferentially be targeted. Many clinicians will consider IWGDF guidelines on the diagnosis and management of
attempting to treat the second vessel supplying the wound DFU, restoration of perfusion in the foot is only part of the
as well, although there is a lack of evidence to support this treatment, which should be provided by a multidisciplinary
approach.7 care team.43 Lack of access to specialist care is associated
with worse foot outcomes. In rural and remote locations
Clinical question and areas where specialist access is challenging, referral
In people with DFU, do revascularisation perfusion out- pathways that address care access (e.g., through virtual
comes predict healing, major amputation, or the need for referral pathways) are essential to establish to provide
further revascularisation? multidisciplinary care.128 Any revascularisation procedure
should therefore be part of a comprehensive care plan that
Recommendation 21 addresses other important issues including: prompt treat-
In a person with diabetes and either a foot ulcer or gangrene ment of concurrent infection, regular wound debridement,
who has undergone revascularisation, objectively assess biomechanical offloading, control of blood glucose, cardio-
adequacy of perfusion e.g., using non-invasive bedside testing. vascular risk reduction, and treatment of co-morbidities.128
Grade Certainty of evidence Moreover, once the ulcer has healed the risk of recurrence
is up to 50% over five years in several studies so preventive
Best Practice Statement
measures need to be taken and many people need long
term follow up by a dedicated foot complication prevention
team.26
Rationale
There are few available data examining the predictive Clinical question
capacity of post-revascularisation perfusion measures for In a person with diabetes, PAD, and a foot ulcer, which
healing or amputation outcomes or for the need for medical treatments should be advised to prevent major
further revascularisation in people with diabetes. How- adverse cardiovascular events (MACE), major adverse limb
ever, adequate perfusion is essential for wound healing events (MALE), and death?
and clinical examination is often too unreliable. Diabetes
related PAD is characterised by atherosclerotic plaque  MACE is defined as a composite of non-fatal stroke, non-
formation that is long and diffuse in nature and more fatal myocardial infarction, and cardiovascular death.
likely to involve distal vascular beds. Frequently, long  MALE is defined as the development of severe lower leg
term patency is not achieved in endovascular treatment ischaemia leading to a vascular intervention or a major
of tibial lesions.127 lower leg amputation.
Regular assessment of perfusion post-revascularisation  These definitions vary slightly between studies.
should therefore be undertaken due to the risk of occlu-
sion and restenosis after intervention. This should be con- People with diabetes and PAD (with or without a foot
ducted in combination with regular assessment of the foot ulcer) are at a very high cardiovascular risk. Cardiovascular
lesion to determine whether healing is indeed taking place. risk factor goals should always be individualised, taking life
It is recommended that revascularisation should aim to expectancy, expected benefit, treatment burden, potential
improve perfusion to the foot as much as possible, which drug interactions, and undesirable treatment effects into
will vary according to the individual. Due to the lack of data account. While taking these considerations into account,
available determining the optimum time frame for follow the Writing Committee suggests the following treatment
up and the likelihood that this may vary depending on the targets to reduce the risk of future major adverse limb and
testing methods being used, a Best Practice Statement cardiovascular events.

Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
22 Robert Fitridge et al.

recommendations of the CLTI guidelines should be adapted

Recommendation 23
to the specific population of people with diabetes. When it
In a person with diabetes and peripheral artery disease, the was felt applicable, the guidelines of the American Diabetes
following target levels should be:
Association (ADA), the European Association for the Study
HbA1c < 8% (< 64 mmol/mol), but higher target HbA1c
value may be necessary depending on the risk of severe of Diabetes (EASD) and other guidelines on peripheral ar-
hypoglycaemia. tery disease (European Society of Cardiology [ESC]-ESVS,
Blood pressure < 140/90 mmHg but higher target levels European Society of Vascular Medicine [ESVM], and ESC-
may be necessary depending on the risk of orthostatic EASD, ESC- European Atherosclerosis Society [EAS]) were
hypotension and other side effects.
used.16e19,22,23,129
Low density lipoprotein target of < 1.8 mmol/L (< 70 mg/dL)
and reduced by at least 50% of baseline. If high intensity PAD runs a more aggressive course in those with diabetes
statin therapy (with or without ezetimibe) is tolerated, mellitus compared with those without diabetes, with an
target levels < 1.4 mmol/L (55 mg/dL) are recommended. elevated risk of lower leg amputation. In addition, the
Grade Certainty of evidence combination of diabetes and PAD is associated with a high
Best Practice Statement risk of developing complications in other vascular beds. As
discussed previously, persons with an ischaemic diabetes
related foot ulcer have an overall five year cardiovascular
Recommendation 24 mortality of around 50%.130 Therefore, according to the
In a person with diabetes and symptomatic peripheral artery
international guidelines of several major vascular and dia-
disease: betes associations, these individuals should be considered
treatment with single antiplatelet therapy should be used, as having a very high cardiovascular risk and should be
treatment with clopidogrel should be considered as first treated as such. On the other hand, they usually have, in
choice in preference to aspirin, addition to peripheral neuropathy, other diabetes related
combination therapy with aspirin (75 mg to 100 mg once
daily) plus low dose rivaroxaban (2.5 mg twice daily)
complications as well as several co-morbidities, resulting in
should be considered for people without a high bleeding a high burden of diseases and multiple medications.30 Many
risk. affected persons are elderly, frail, and are living in vulner-
Grade Certainty of evidence able socio-economic circumstances with a low quality of
Best Practice Statement life.131,132 It is therefore essential that cardiovascular risk
factor management in these people should be individu-
alised, tailored, and should be part of a shared decision
Recommendation 25 making process, taking life expectancy, diabetes related
complications and co-morbidities, expected benefit, treat-
In a person with type 2 diabetes and peripheral artery
disease:
ment burden, drug interactions, and undesirable treatment
with an eGFR > 30 mL/min/1.73m2, a sodium glucose effects into account. This care should be provided by
cotransporter-2 (SGLT-2) inhibitor or a glucagon like healthcare worker(s) with sufficient expertise in treating
peptide 1 receptor agonist with demonstrated cardiovascular risk factors and glycaemia, preferably by
cardiovascular disease benefit should be considered, person(s) who are part of the multidisciplinary team for
irrespective of the blood glucose level.
SGLT-2 inhibitors should not be started in drug naïve
diabetes related foot care.
people with a diabetes related foot ulcer or gangrene and
temporary discontinuation should be considered in people Glycaemic goals. As stated in the ADA and ESC-EASD
already using these drugs, until the affected foot is healed. guidelines, near normal glycaemia with HbA1c level below
Grade Certainty of evidence 7.0% (53 mmol/mol) will decrease microvascular compli-
Best Practice Statement cations.18,22 Tighter glucose control initiated early in the
course of diabetes in younger individuals leads to a reduc-
tion in macrovascular complications, i.e., cardiovascular
outcomes, over a 20 year timescale. Such glucose control
Rationale can have beneficial effects on microvascular complications
The Writing Committee decided to not write their own in a shorter period of time. However, when blood glucose
guidelines on pharmacological interventions in people with lowering agents are used that have the risk of severe
diabetes, PAD, and a foot ulcer or gangrene in order to hypoglycaemia, this can increase the risk of cardiovascular
reduce cardiovascular risk or to prevent major limb events events and death, as detailed in the ADA and ESC-EASD
as defined above. There are already a number of guidelines guidelines.18,129 As many people with a DFU and PAD also
on cardiovascular risk prevention in people with diabetes have atherosclerotic disease in other vascular beds, tight
and cardiovascular disease, and thus another guideline glucose control can be harmful. The risk of hypoglycaemia is
would have little added value. It was decided to base the markedly lower when people are only treated with met-
Best Practice Statements on the GVG for CLTI produced by formin, a sodium glucose cotransporter-2 inhibitor or a
the ESVS, SVS, and World Federation of Vascular Societies glucagon like peptide 1 receptor agonist. Tight glucose
(WFVS),20 as these address the specific population of peo- control is often not indicated in people with PAD and a DFU
ple with CLTI. However, it was also felt that some of the due to the risk of hypoglycaemia outweighing the potential
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 23

benefit. The ADA recommends in the 2022 Standards of effectiveness of PCSK9 inhibitors in people with diabetes,
Care to aim for an HbA1c < 8% (< 64 mmol/mol) in such PAD, and a foot ulcer or gangrene. In addition, the use of
persons and the ESC-EASD 2019 guideline for levels below these expensive drugs is a problem for many countries in
8 e 9% (< 64 e 75 mmol/l).18,129 However, the target chosen the world, and for these reasons a recommendation on LDL
will depend on factors such as age, duration of diabetes, level below 1.0 mmol/L (40 mg/dL) for this specific popu-
complications, co-morbidities, and risk of hypoglycaemia. lation was not included, but it is acknowledged that in
These target HbA1c levels are higher than the level formu- several countries PCSK9 inhibitors are used to reach these
lated in the GVG for CLTI (< 7.0%, 53 mmol/mol), but as goals in those with recurrent cardiovascular events.
discussed above it is concluded that the risk of such tight In line with the other cardiovascular risk reduction in-
blood glucose control is too high in this specific population. terventions in these usually frail, multimorbid individuals,
treatment and its goals should be based on shared decision
Blood pressure goals. The ESC-EASD guidelines state that
making and should be individualised after careful weighting
RCTs have demonstrated the benefit (reduction of stroke,
of the benefits, harms, and costs. The LDL (and other)
coronary events, and kidney disease) of lowering systolic BP
treatment targets in the recommendation should not be
to < 140 mmHg and diastolic BP to < 90 mmHg.18 Usually,
interpreted as absolute goals but more as desired goals.
multiple drugs are necessary to reach these levels in people
Even if the goal is only partially met, it can result in a
with diabetes. In younger people (e.g., younger than 65
marked reduction in cardiovascular events in these very
years) levels below 130/80 mmHg can be considered if
high risk people. Although very low LDL levels are perhaps
there are no contraindications for such tight blood pressure
not achievable in all, LDL reductions of up to 50% can be
control and the risk of orthostatic hypotension is low. Both
achieved in many with the aforementioned potent statins
the ADA and ESC-EASD stress the importance of individu-
(and ezetimibe), with marked reduction in cardiovascular
alised treatment as overly aggressive blood pressure
risk.16
lowering is not without risk in the usually elderly with a DFU
and those with multiple diabetes related complications and
co-morbidities. Therefore, in these people blood pressures Additional therapies
< 140/90 mmHg are recommended, but in younger in-
Antithrombotic therapy. The subsequent advice on anti-
dividuals (e.g., < 65 years) and with a small risk of adverse
platelet therapy is in line with the recent ESVS antith-
effects of the treatment, lower target levels might be
rombotic guidelines.137 All guidelines strongly recommend
considered.
treatment with a single antiplatelet agent in persons with
Lipid goals. The ADA and EASD guidelines recommend in symptomatic cardiovascular disease, or more specifically
persons with diabetes and atherosclerotic cardiovascular chronic limb threatening ischaemia (CLTI). These drugs
disease an LDL target of < 1.8 mmol/L (70 mmol/L).21 In reduce the risk of cardiovascular events; for the increased
line with the lower the better approach, recent trials sug- risk of gastric bleeding in aspirin treated individuals, a
gest that lower levels of LDL of < 1.4 mmol/L (55 mg/dL) proton pump inhibitor as additional treatment should be
can be beneficial in persons with a very high cardiovascular considered. There is less consensus regarding which drug to
risk. Therefore, the recent ESC-EASD and ESC-EAS guidelines choose, clopidogrel or aspirin. The ADA and ESC-EASD
recommend that such very low LDL levels should be the guideline advises aspirin as first choice in persons with
target in these individuals.18,19 In those with recurrent diabetes and a cardiovascular event but did not specify for
events within two years, even LDL levels < 1.0 mmol/L (40 the presence of PAD.18,21 In the recent ESVM, ESC-ESVS,
mg/dL) are suggested as target in ESC-EAS guidelines.19 and GVG guidelines, clopidogrel is considered as the anti-
With statin therapy such as rosuvastatin 20 e 40 mg or platelet agent of choice in those with PAD. This recom-
atorvastatin 40 e 80 mg, marked reductions of LDL mendation is in particular based on The Clopidogrel versus
cholesterol can be achieved if these relatively simple Aspirin in Patients at Risk for Ischaemic Events (CAPRIE)
treatments are tolerated. When the target is not reached trial, in which clopidogrel was more effective in reducing
ezetimibe can be added, which is available in combination cardiovascular risk without an increased risk of bleeding.133
tablets with both statins. These treatments have limited It should be noted that only a subset of participants in this
side effects in most (but not all) people and are relatively trial had PAD, of which only 21% had diabetes. Also, a meta-
inexpensive. According to the recent ESC-EASD and ESC-EAS analysis did not show any benefit from aspirin for those
guidelines, an LDL level below 1.0 mmol/L (40 mg/dL) can with PAD.134 A post hoc subanalysis of the CAPRIE trial
be the target in people with recurrent cardiovascular events showed that clopidogrel was superior to aspirin in reducing
(within two years), based on a limited number of RCTs in recurrent ischaemic events in those with diabetes.135 The
which relatively few participants with CLTI and diabetes relative risk reduction was comparable with those without
were included. To reach the aforementioned very low LDL diabetes, but due to the greater number of events among
levels, additional treatment with a PCSK9 inhibitor will be people with diabetes, the absolute risk reduction was even
necessary in a proportion of people. PCSK9 inhibitors are larger. Given the potential benefit, it is suggested in a
monoclonal antibodies that have limited side effects but Conditional Recommendation that clopidogrel should be
have the drawback of high costs, parenteral administration, considered as first choice, in line with the aforementioned
and at present there is very limited evidence of the cost guidelines.
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
24 Robert Fitridge et al.

As an additional alternative to single antiplatelet therapy, bypass surgery using an autogenous or prosthetic conduit
combination therapy with aspirin (100 mg once daily) plus may be considered for single antiplatelet therapy to
low dose rivaroxaban (2.5 mg twice daily) should be improve graft patency.137
considered for those with low bleeding risk to prevent car- Arterial duplex scanning post-autologous vein bypass
diovascular events as well as reduce extremity ischaemic surgery is generally advised post-procedure to detect graft
events in those with CLTI, as suggested by the GVG, ESVM, stenoses. The benefits of post-procedure surveillance
and ESC-EASD guidelines and the 2023 ADA Standards of following endovascular intervention remain uncertain;
Care.16,20,23,129 This suggestion is based on the COMPASS following local protocols is suggested.
trial in which this combination therapy was more effective
than aspirin but was also associated with an increased risk of Glucose lowering therapies. In recent years it has become
clinically relevant bleeding, mostly gastrointestinal.136 In this increasingly clear that several sodium glucose
trial approximately 38% had diabetes mellitus and the cotransporter-2 (SGLT-2) inhibitors and glucagon like pep-
benefit of the combination therapy seemed similar in those tide 1 receptor (GLP-1) agonists, which were originally
with and without diabetes. Given this limited evidence base developed to lower blood glucose levels, can also have
and the added treatment burden for this frequently vulner- beneficial cardiovascular effects in persons with type 2
able cohort, a Best Practice Statement in line with the ESVS diabetes.21 These effects are independent of their blood
and ADA recommendations was made.129,137 It should be glucose lowering effect. To what extent this benefit can also
noted that in the COMPASS trial in addition to a high be observed in those with type 1 diabetes mellitus, in
bleeding risk of rivaroxaban, other exclusion criteria included whom glucose management with these drugs only has a
end stage renal disease, severe heart failure, recent stroke, limited (SGLT-2 inhibitors) or no (GLP-1 agonists) role to
history of haemorrhagic or lacunar stroke, and poor life ex- play, remains to be established. In individuals with an eGFR
pectancy.138 A network meta-analysis showed no superiority < 30 mL/min/1.73m2, these drugs are contraindicated.
for aspirin with rivaroxaban over clopidogrel alone for the Therefore, it is advised to consider these drugs in type 2
primary composite endpoint in the chronic PAD subgroups of diabetes mellitus and peripheral artery disease with an
CAPRIE and COMPASS.139 Therefore in the absence of a RCT eGFR > 30 mL/min/1.73m2 after careful review and
directly comparing the two, both clopidogrel alone and possibly adjustment of other blood glucose lowering
aspirin with rivaroxaban are reasonable choices for second- medication to prevent hypoglycaemia, but for SGLT-2 in-
ary cardiovascular prevention for patients with chronic hibitors there are additional caveats.
symptomatic PAD, but the risk of bleeding and contraindi- The SGLT-2 inhibitor canagliflozin was associated with an
cations should be taken into account when discussing the increased risk of amputation in an RCT. This was not a pre-
options with the patient.137 The ESVS antithrombotic specified endpoint and was not observed in the other SGLT-
guidelines recommend that those not at high risk of bleeding 2 inhibitor trials143 or in long term prospective studies, as
who undergo an endovascular intervention for lower ex- concluded in the ADA-EASD 2022 consensus report.144 In
tremity PAD may be considered for a one to six month addition, in post hoc analyses, these drugs had beneficial
course of dual antiplatelet therapy (aspirin plus clopidogrel) cardiovascular and renal effects in people with peripheral
to reduce the risk of MACE and MALE followed by single artery disease.145 However, individuals with foot ulcers
antiplatelet therapy.137 Similarly, those undergoing endovas- were frequently excluded in SGLT-2 inhibitor trials and there
cular intervention who are not at high risk of bleeding should is a second caveat to be considered. Diabetes related
be considered for aspirin (75 e 100 mg daily) and low dose ketoacidosis is a rare but serious side effect of SGLT-2 in-
rivaroxaban (2.5 mg twice daily) to reduce the risk of MACE hibitors and prolonged fasting, acute illness and the peri-
and MALE.137,140 If the bleeding risk is considered to be high, operative period predispose to developing ketoacidosis. In
single antiplatelet therapy should be used post-intervention. these situations, the ADA-EASD recommend temporary
If clopidogrel is used in addition to aspirin and low dose discontinuation of the medication, i.e., three days prior to
rivaroxaban after endovascular intervention, clopidogrel surgery.144 Like those with PAD, a diabetes related foot
should only be used for < 30 days as with longer term use ulcer or gangrene have a high risk of developing a foot
the bleeding risk is likely to outweigh the benefit.137,141 infection or to undergo one or more (urgent) surgical pro-
The ESVS antithrombotic guidelines recommend that cedures, it is suggested for pragmatic reasons that SGLT-2
those undergoing infrainguinal endarterectomy or bypass inhibitors should not be started in drug naïve individuals
surgery who are not at high risk of bleeding should be and that temporary discontinuation should be considered in
considered for aspirin (75 e 100 mg daily) and low dose those already using these drugs, until the affected foot is
rivaroxaban (2.5 mg twice daily) to reduce the risk of MACE healed.
and MALE. Those persons undergoing infrainguinal bypass
surgery with autogenous vein who are not at high bleeding
risk may be considered for treatment with vitamin K Postscript
antagonist to improve graft patency.137,142 The targets discussed in this text are based on reduction of
Those undergoing infrainguinal bypass with a prosthetic cardiovascular events, but it should be noted that this is a
graft may be considered for single antiplatelet therapy. composite endpoint and the definition between trials dif-
Persons at high risk of bleeding undergoing lower extremity fers. MALE is also sometimes differently defined and the
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
Intersocietal Guidelines on PAD in People with DM and Foot Ulcer 25

evidence for reducing lower limb events in persons with have been developed to deal with heavily calcified lesions.
diabetes, PAD, and a foot ulcer by pharmacological treat- Venous arterialisation has also been introduced to attempt
ment is scarce. For this reason, a specific recommendation to revascularise those with no option for revascularisa-
on this topic could not be made. tion.147,148 The role and indications for these interventions
in the general population with CLTI, and in particular those
FUTURE RESEARCH PRIORITIES with diabetes, remains to be clarified.
One of the main limitations of this guideline is the lack of Identify effective regenerative therapies (e.g., cell or gene
prospective randomised trials, inconsistency of classification based) to improve foot perfusion in persons with DFU and
and outcomes reported, and lack of separation of outcome PAD who are not candidates for standard revascularisation.
for people with CLTI with and without diabetes. Data Angiogenesis (formation of new blood vessels from
reporting on PAD in relation to diagnosis, prognosis, and existing ones) is important for the development of arterial
management overwhelmingly relate to the general popu- collateral formation in response to arterial occlusion and
lation. There is a paucity of high level evidence for diagnosis also for wound healing. Diabetes and hyperglycaemia are
and management of those with DFU or gangrene, with associated with impaired angiogenesis. A number of cell,
studies frequently including only persons with intact feet or gene, and protein based therapeutic approaches have, and
inadequately detailing (or controlling for) confounding fac- are, being trialled for both no option CLTI and wound
tors including presences of neuropathy, ulcer, infection, or healing in diabetes. There are currently no therapies that
other contributors to poor outcomes. Moreover, few studies have proven beneficial and trials are ongoing.149
in CLTI cohorts provide subanalysis for those with diabetes,
although they are likely to make up the majority of the
CONTRIBUTION OF AUTHORS
included population. As such, there is clearly a need for
further research into this unique subgroup of individuals The Writing Committee was chaired by R.F. (on behalf of
with diabetes, so that outcomes around the world can be the IWGDF), with R.H. (on behalf of the ESVS) and J.L.M (on
improved. The Writing Committee considers there are a behalf of the SVS) as co-chairs and supported by N.S. (on
number of priority areas for future research. The systematic behalf of the IWGDF). V.C. acted as scientific secretary. The
review of the prognostic capacity of bedside vascular testing three organisations involved were each tasked to select six
to predict DFU healing and amputation outcomes demon- well recognised experts to create an international, multi-
strated a lack of investigations of sufficient quality for disciplinary, writing committee of 18 members in total. Care
several widely available tests including TBI and TcPO2, with was taken to have a global, multidisciplinary group that
inconsistent use of measurement thresholds and a lack of included disciplines such as vascular surgery, angiology,
data examining the effect of combining test outcomes. New interventional radiology, vascular medicine, endocrinology,
technologies to develop optimal tools and measures of foot epidemiology, and podiatry.
perfusion for people with DFU and PAD to guide revascu- All members of the Writing Committee were involved in
larisation therapies would be invaluable in guiding revas- summarising the available evidence in the supporting sys-
cularisation strategies for individuals and for determining tematic reviews, that are published separately, and in
when more aggressive strategies are indicated. writing this guideline. Several members (the chairs, scien-
tific secretary, N.S, and M.S.C.) were assigned to write in-
Further questions dividual sections of the guideline, and all authors reviewed
Which group of people with diabetes and a DFU, tissue loss, and discussed the evidence obtained, the evidence to de-
or gangrene most benefit from urgent revascularisation, and cision items according to GRADE, and each recommenda-
who may benefit from an initial expectant management? tion during group meetings. All authors reviewed and
The Writing Committee has made a Best Practice State- agreed with the final document before societal review and
ment attempting to define which people are likely to subsequent submission for endorsement. All members of
benefit most from urgent vascular assessment and revas- the working group undertook Level 1 GRADE training, and
cularisation. Further studies to clarify person and limb the several working group members undertook Guideline
related factors are needed and such predictions may be Methodology training (McMaster University).
facilitated by new prediction methods such as machine
learning.146 ACKNOWLEDGEMENTS
Do newer endovascular revascularisation adjuncts and We would like to thank the following external experts for
techniques developed for infrapopliteal revascularisation their review of our PICOs for clinical relevance and the
positively impact on patency rates and person centred guideline document: Sriram Narayanan (Singapore), Rica
endpoints (amputation free survival, improved wound Tanaka (Japan), Ismail Cassimjee (South Africa), Xu Jun
healing, and health related quality of life) in those with (China), Heidi Corcoran (Hong Kong), Yamile Jubiz
diabetes, PAD, and a foot ulcer? (Colombia), Tsvetalina Tankova (Bulgaria), and our patient
A number of new technologies have been developed to representatives. Production of the 2023 IWGDF Guidelines
enhance patency of endovascular interventions, including was supported by unrestricted grants from: Advanced Ox-
drug eluting balloons and stents, and bioresorbable vascular ygen Therapy Inc., Essity, Mölnlycke, Reapplix, and Urgo
scaffolds and stents. Atherectomy and lithotripsy devices Medical. These sponsors did not have any communication
Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020
26 Robert Fitridge et al.

related to the systematic reviews of the literature or related 16 Frank U, Nikol S, Belch J, Boc V, Brodmann M, Carpentier PH,
to the guidelines with working group members during the et al. ESVM Guideline on peripheral arterial disease. Vasa
2019;48:1e79.
writing of the guidelines and have not seen any guideline or 17 Aboyans V, Ricco JB, Bartelink ML, Björck M, Brodmann M,
guideline-related document before publication. Cohner T, et al. [2017 ESC Guidelines on the Diagnosis and
Treatment of Peripheral Arterial Diseases, in collaboration with
the European Society for Vascular Surgery (ESVS)]. Kardiol Pol-
APPENDIX A. SUPPLEMENTARY DATA ska 2017;75:1065e160.
Supplementary data to this article can be found online at 18 Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A,
https://doi.org/10.1016/j.ejvs.2023.07.020 Delgado V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes,
and cardiovascular diseases developed in collaboration with the
EASD. Eur Heart J 2020;41:255e323.
19 Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M,
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Please cite this article as: Fitridge R et al., The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot
Ulcer, European Journal of Vascular and Endovascular Surgery, https://doi.org/10.1016/j.ejvs.2023.07.020