• Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of peripheral arterial disease. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2006 Oct. 37 p. (SIGN publication; no. 89). [129 references]

Peripheral arterial disease (PAD)

Diagnosis
Evaluation
Management
Prevention
Risk Assessment
Treatment

Cardiology
Family Practice
Internal Medicine
Preventive Medicine

Advanced Practice Nurses
Nurses
Occupational Therapists
Patients
Physical Therapists
Physician Assistants
Physicians
Public Health Departments

To provide recommendations based on evidence for best practice in the management of patients with lower limb peripheral arterial disease (PAD)

Patients with symptomatic peripheral arterial disease (PAD) in the form of intermittent claudication

This guideline is not intended for use in the following populations:

• Patients without evidence of existing vascular disease
• Patients with critical limb ischaemia—a severe manifestation of PAD characterized by chronic ischaemic rest pain, ulcers, or gangrene

Risk Management/Prevention

1. Smoking cessation
2. Cholesterol lowering (statin therapy)
3. Glycaemic control
4. Weight reduction
5. Blood pressure control
6. Antiplatelet therapy

Diagnosis

1. Investigations in primary care
2. Referral to secondary care and investigations
3. Non-invasive imaging (computed tomography angiography)

Treatment

1. Treatment with licensed drugs, including cilostazol and naftidrofuryl
2. Treatment with statins
3. Exercise therapy
4. Referral to vascular specialist and vascular interventions under limited circumstances with consideration of the TransAtlantic Inter-society guidelines

Note: The following interventions were considered but not recommended:

• Digital subtraction arteriography as the primary imaging modality for patients with peripheral arterial disease
• Oxpentifylline for the treatment of intermittent claudication
• Inositol nicotinate for the treatment of intermittent claudication
• The use of oral prostaglandin therapy in patients with intermittent claudication

• Level of cardiovascular risk
• Incidence of cardiovascular and cerebrovascular events
• Mortality
• Sensitivity and specificity of diagnostic analysis
• Mean walking distance
• Quality of life
• Exercise tolerance

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases

The evidence base for this guideline was synthesised in accordance with Scottish Intercollegiate Guidelines Network (SIGN) methodology. A systematic review of the literature was carried out using an explicit search strategy devised by a SIGN Information Officer. Databases searched include Medline, Embase, Cinahl, and the Cochrane Library. The year range covered was 1994 to 2004. Internet searches were carried out on various websites including the New Zealand Guidelines Programme, NELH Guidelines Finder, and the US National Guidelines Clearinghouse. The Medline version of the main search strategies can be found on the SIGN Website, in the section covering supplementary guideline material. The main searches were supplemented by material identified by individual members of the development group. All selected papers were evaluated by two members of the group using standard SIGN methodological checklists before conclusions were considered as evidence.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Levels of Evidence

1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias

1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2++: High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+: Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal

3: Non-analytic studies (e.g. case reports, case series)

4: Expert opinion

Systematic Review with Evidence Tables

Expert Consensus

Grades of Recommendation

Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.

A: At least one meta-analysis, systematic review of randomized controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results

B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++

D: Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Good Practice Points: Recommended best practice based on the clinical experience of the guideline development group

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

National Open Meeting

The national open meeting is the main consultative phase of Scottish Intercollegiate Guidelines Network (SIGN) guideline development. The national open meeting for this guideline was held on 11 October 2004 and was attended by representatives of all the key specialties relevant to the guideline. The draft guideline was also available on the SIGN website for a limited period at this stage to allow those unable to attend the meeting to contribute to the development of the guideline.

Peer Review

All SIGN guidelines are reviewed in draft form by independent expert referees, who are asked to comment primarily on the comprehensiveness and accuracy of interpretation of the evidence base supporting the recommendations in the guideline. A number of general practitioners (GPs) and other primary care practitioners also provide comments on the guideline from the primary care perspective, concentrating particularly on the clarity of the recommendations and their assessment of the usefulness of the guideline as a working tool for the primary care team. The draft is also sent to a lay reviewer in order to obtain comments from the patient's perspective. The comments received from peer reviewers and others are carefully tabulated and discussed with the chairman and with the guideline development group. Each point must be addressed and any changes to the guideline as a result noted or, if no change is made, the reasons for this recorded.

As a final quality control check prior to publication, the guideline and the summary of peer reviewers' comments are reviewed by the SIGN Editorial Group for that guideline to ensure that each point has been addressed adequately and that any risk of bias in the guideline development process as a whole has been minimised. Each member of the guideline development group is then asked formally to approve the final guideline for publication.

Note from the Scottish Intercollegiate Guidelines Network (SIGN) and National Guideline Clearinghouse (NGC): In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the full-text guideline document.

The grades of recommendations (A–D) and levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) are defined at the end of the "Major Recommendations" field.

Cardiovascular Risk Reduction

Smoking Cessation

D - Patients with peripheral arterial disease should be actively discouraged from smoking.

Cholesterol Lowering

A - Lipid lowering therapy with a statin is recommended for patients with peripheral arterial disease and total cholesterol level >3.5 mmol/L.

Glycaemic Control

B - Optimal glycaemic control is recommended for patients with peripheral arterial disease and diabetes in order to reduce the incidence of cardiovascular events.

Weight Reduction

D - Obese patients with peripheral arterial disease should be treated to reduce their weight.

Blood Pressure Control

A - Hypertensive patients with peripheral arterial disease should be treated to reduce their blood pressure.

Antiplatelet Therapy

A - Antiplatelet therapy is recommended for patients with symptomatic peripheral arterial disease.

Referral, Diagnosis, and Investigation

Investigations in Secondary Care

Digital Subtraction Arteriography

D - Digital subtraction arteriography is not recommended as the primary imaging modality for patients with peripheral arterial disease.

Computed Tomography Angiography

A - Non-invasive imaging modalities should be employed in the first instance for patients with intermittent claudication in whom intervention is being considered.

Treatment of Symptoms

Licensed Drug Therapy for Peripheral Arterial Disease

Cilostazol

A - Patients with intermittent claudication, in particular over a short distance, should be considered for treatment with cilostazol.

A - If cilostazol is ineffective after three months, or if adverse effects prevent compliance with therapy, the drug should be stopped.

Naftidrofuryl

A - Patients with intermittent claudication and who have a poor quality of life may be considered for treatment with naftidrofuryl.

Oxpentifylline

A - Oxpentifylline is not recommended for the treatment of intermittent claudication.

Inositol Nicotinate

B - Inositol nicotinate is not recommended for the treatment of intermittent claudication.

Unlicensed Research Drugs and Procedures

Statins

A - Statins should be given for risk factor management in patients with intermittent claudication and total cholesterol level >3.5 mmol/L.

Prostaglandins

A - The use of oral prostaglandin therapy in patients with intermittent claudication is not recommended.

Exercise Therapy

A - Patients with intermittent claudication should be encouraged to exercise.

Vascular Intervention

D - Endovascular and surgical intervention are not recommended for the majority of patients with intermittent claudication.

D - For those with severe disability or deteriorating symptoms, referral to a vascular specialist is recommended.

D - The TransAtlantic Inter-society consensus guidelines should be used when advising patients about possible interventions.

Definitions:

Levels of Evidence

1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias

1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2++: High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+: Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal

3: Non-analytic studies (e.g. case reports, case series)

4: Expert opinion

Grades of Recommendation

Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.

A: At least one meta-analysis, systematic review of randomized controlled trials (RCTs), or RCT rated as 1++ and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results

B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++

D: Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Good Practice Points: Recommended best practice based on the clinical experience of the guideline development group

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

• Reduced cardiovascular risk
• Accurate diagnosis of peripheral arterial disease (PAD)
• Reduced morbidity and mortality associated with PAD
• Improved quality of life

Adverse effects of drug therapy

This guideline is not intended to be construed or to serve as a standard of care. Standards of care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge and technology advance and patterns of care evolve. Adherence to guideline recommendations will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results. The ultimate judgement must be made by the appropriate healthcare professional(s) responsible for clinical decisions regarding a particular clinical procedure or treatment plan. This judgement should only be arrived at following discussion of the options with the patient, covering the diagnostic and treatment choices available. It is, however, advised that significant departures from the national guideline or any local guidelines derived from it should be fully documented in the patient's case notes at the time the relevant decision is taken.

Implementation of national clinical guidelines is the responsibility of each National Health Service Board and is an essential part of clinical governance. It is acknowledged that every Board cannot implement every guideline immediately on publication, but mechanisms should be in place to ensure that the care provided is reviewed against the guideline recommendations and the reasons for any differences assessed and, where appropriate, addressed. These discussions should involve both clinical staff and management. Local arrangements may then be made to implement the national guideline in individual hospitals, units and practices, and to monitor compliance. This may be done by a variety of means including patient-specific reminders, continuing education and training, and clinical audit.

Key points for implementation and audit and resource implications are identified in the original guideline document.

Living with Illness
Staying Healthy

Effectiveness

• Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of peripheral arterial disease. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2006 Oct. 37 p. (SIGN publication; no. 89). [129 references]

Not applicable: The guideline was not adapted from another source.

2006 Oct

Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]

Scottish Executive Health Department

Not stated

Guideline Development Group: Professor Gerry Fowkes (Chair) Professor of Epidemiology, Public Health Sciences, University of Edinburgh; Ms Margaret Armitage, Vascular Liaison Nurse, Greater Glasgow Primary Care Trust; Professor Jill Belch, Professor of Vascular Medicine, Ninewells Hospital and Medical School, Dundee; Mr Graham Bell, Lay representative, Penicuik; Ms Julie Brittenden, Senior Lecturer and Consultant Vascular Surgeon, Aberdeen Royal Infirmary; Dr Henry Doig, Lay representative, Glasgow; Dr Ian Gillespie, Vascular (Interventional) Radiologist, Royal Infirmary of Edinburgh; Ms Margaret Greene, Vascular Technologist, Southern General Hospital, Glasgow; Ms Alison Howd, Consultant Vascular Surgeon, Queen Margaret Hospital, Dunfermline; Dr Gordon Isbister, General Practitioner, Beith; Dr Moray Nairn, Programme Manager, SIGN Executive; Dr Jackie Price, Clinical Lecturer, Public Health Sciences, University of Edinburgh; Ms May Roseburgh, Clinical Nurse Specialist, Royal Infirmary of Edinburgh; Ms Mairi Ross, Senior Vascular Physiotherapist, Raigmore Hospital, Inverness; Ms Helen Scott, Superintendent Physiotherapist WESTMAR, Southern General Hospital, Glasgow; Ms Valerie Sinclair, Vascular Nurse, Stirling Royal Infirmary; Ms Christine Smith, Vascular Liaison Nurse, Raigmore Hospital, Inverness; Mrs Ailsa Stein Information Officer, SIGN Executive; Dr Rebecca Walton, Specialist Registrar in Public Health, Lothian NHS Board; Dr Olivia Wu, Health Economist, Reproductive and Maternal Medicine, Division of Developmental Medicine, University of Glasgow

Declarations of interests were made by all members of the guideline development group. Further details are available from the Scottish Intercollegiate Guidelines Network (SIGN) Executive.

This NGC summary was completed by ECRI on November 28, 2006.