The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) recently published a comprehensive set of guidelines for the management of venous leg ulcers (VLU) in the Journal of Vascular Surgery.¹ The SVS/AVF guidelines were a direct result of the Sixth Pacific Vascular Symposium, which was sponsored by the AVF, and this document was viewed as a major method to accomplish the goal of the symposium’s initiative—to decrease VLUs by 50% in the next decade. Like other SVS/AVF guidelines, they are usually prepared by specialty societies, which validate and transfer new techniques through evidenced-based systematic reviews. As a whole, guidelines are best practices to achieve the best quality outcomes for the most reasonable expenditure of the health care dollar.

Several studies have shown that using VLU guidelines can improve care, lower the incidence of new VLUs in a population, reduce recurrence and contain the costs of treating VLU. Clinical care guidelines should transfer new techniques that optimally have been validated by properly conducted RCTs. In addition, these protocols should provide enhanced quality of care without a dramatic increase in cost. The Venous Ulcer Initiative Committee of the AVF, which met telephonically at least once a month, was instrumental in advancing the development of the VLU guidelines.

As a result, this committee responded to a RFP from the SVS Guidelines Committee for new vascular guidelines, and our proposal for a VLU guideline was approved by the SVS. A subsequent systematic analysis of 14 published VLU guidelines was performed to identify areas of disagreement and weak recommendations for further research and refinement.² This gap analysis showed several important areas to explore in the new SVS/AVF guidelines, which were not addressed in the previous guidelines (as shown below).

Knowledge gaps not well-addressed in previous VLU guidelines

• Role of advanced wound dressings
• Role of superficial venous surgery
• Role of iliac obstruction> Need for IVUS & stenting
• Perforators> When to treat?
• Need for P.T. to improve ankle mobility

The VLU guideline process

The SVS/AVF Guidelines Committee, under co-editors Tom O’Donnell and Marc Passman, was divided into six working groups, each with the specific purpose of analyzing one major aspect of venous ulcer management. The Diagnosis group was chaired by Marc Passman and with members Rob McLafferty, Bill Marston, Lori Pounds and Peter Henke. The Compression group was chaired by Fedor Lurie and with members Tom Wakefield, Cynthia Shortell, Monika Gloviczki, Bo Eklof and Hugo Partsch. The Wound Care group was co-chaired by Bill Ennis and Bill Marston, and was also comprised of Emily Cummings, Lori Pounds and Tom O’Donnell. The Surgery/Endovascular group was co-chaired by Bob Kistner and Mike Dalsing with the help of Julianne Stoughton, David Gillespie, Peter Gloviczki, Bo Eklof and “Raj” Raju. The Ancillary group was chaired by Monika Gloviczki with members Cynthia Shortell, Bill Ennis and Julianne Stoughton. Finally, the Primary prevention group was chaired by Peter Henke with Fedor Lurie, Emily Cummings and Mike Dalsing.

The committee developed a critical set of questions to provide overall guidance to the project:

1. What are the best strategies for treatment of active versus healed ulcers?
2. What are the best strategies for prevention of recurrence?
3. What are the best strategies for prevention of the post-thrombotic syndrome?

Since guideline development involves sifting through massive amounts of data to provide a consensus on the evidence for treatment of a specific condition, the committee evaluated several possible processes for the format of each section:

1. Total adoption of existing guidelines
2. Adaptation of existing guidelines
3. Build on existing guidelines with a complimentary literature search
4. The development of novel recommendations from a systematic review and meta-analysis of relevant literature.

Two areas were chosen for a systematic review and meta-analysis, which was performed under M. Hassan Murad’s leadership and his team from the Mayo Clinic’s Department of Medicine and the Knowledge and Encounter Research Unit:

1. Compression
2. Surgery/endovascular

Following multiple reviews by each section, as well as by the co-editors, the entire VLU guideline document and the two systematic reviews were assessed by the SVS Document Committee, and their comments were incorporated into the final revision. Since the committee invited other societies to endorse the guideline, we also responded to the helpful comments of the American College of Phlebology and the Union Internationale de Phlebologie, both of whom endorsed the VLU guidelines. Most recently, the board of the American College of Wound Healing and Tissue Repair voted for endorsement of the guidelines.

The standard grade method was used,³ as in other SVSsponsored guidelines, which consists of two components. The strength of the recommendation or the confidence that adherence to the recommendation will do more good than harm was divided into:

1. Strong- (we recommend) favoring benefit over harm
2. Weak- (we suggest) where the benefits are closely balanced by the risk.

The second component—the quality of evidence, which is defined as the extent to which confidence in an estimate of affect—is sufficient to support a particular recommendation. It was graded as [A], [B], or [C] using standard evidenced-based methodological criteria.

The VLU guidelines contain a total of 65 guideline recommendations. Overall, the evidence level for venous ulcer management is mostly of moderate strength and, as a consequence, most recommendations as a whole received lower grades. There were 14 Grade 2, Level B (18.6%); 40 Grade 2, Level C (53.3%); and eight Best Practice (12%) recommendations. The final 90-page document, which included the guidelines and the two evidence-based analyses, was published as a supplement in the Journal of Vascular Surgery.¹

Specifically selected guidelines

Guideline 3.9: Venous Duplex Ultrasound

We recommend comprehensive venous duplex ultrasound examination of the lower extremity in all patients with suspected venous leg ulcer. [GRADE -1; LEVEL OF EVIDENCE -B]

Patients presenting to a specialist with a leg ulcer that clinically appears to be of venous origin require duplex ultrasound to determine:

• E (etiology)
• A (anatomy)
• P (Pathophysiology)

This diagnostic test should determine the anatomic levels involved, as well as the cause of reflux, obstruction, or a combination. This knowledge becomes essential to guiding treatment. Assessment of arterial perfusion by Doppler ABIs is also recommended.

Guideline 3.12: Venous Disease Classification

We recommend that all patients with venous leg ulcer should be classified based on venous disease classification assessment, including clinical CEAP, revised venous clinical severity scoring (VCSS ) and a venous disease specific quality of life (QOL) assessment. [BEST PRACTICE]

The advent of electronic health records facilitates the use of the CEAP classification and a practitioner- administered revised (2010) Venous Clinical Severity Score (VCSS) is a simple sequential method for following the clinical course of a patient with VLU. Complimenting these two modalities is a disease-specific patient-reported QoL, such as the Charing Cross Venous Ulcer Questionnaire and the Vilalta score.

Historically, the two key methods for promoting VLU healing are compression and wound care, which are discussed below.

Guideline 5.1: Compression – Ulcer Healing

In a patient with a venous leg ulcer, we recommend compression therapy over no compression therapy to increase venous leg ulcer healing rate. [GRADE -1; LEVEL OF EVIDENCE -A]

Guideline 5.3: Multi-Component Compression Bandage

We suggest the use of multi-component compression bandage over single component bandages for the treatment of venous leg ulcers. [GRADE -2; LEVEL OF EVIDENCE -B]

Compression has been clearly shown to improve ulcer healing over no compression. Four layer bandages (4 LB) are typical of multi-component bandages and consist of four components:

1. Orthopedic wool
2. Crepe bandage
3. Elastic bandage
4. Elastic cohesive (outer) bandage

While increasing the interface pressure, the composition of the bandage also changes the elastic property of the final bandage so that the 4LB is less elastic and stiffer. The commissioned systematic review and meta-analysis by the Mayo group demonstrated that compression is better than no compression and moderate quality evidence exists to favor multicomponent compression over single component compression.4 Unfortunately, few RCTs provide evidence for the use of compression to prevent recurrence. Higher compression elastic stockings (34-46mmHg), have been shown to be more effective than lower pressure stockings, but are affected by a reduced patient compliance rate.

Guideline 4.4: Surgical Debridement - Wound Care

We recommend that surgical debridement be performed for venous leg ulcers with slough, non-viable tissue or eschar. Serial wound assessment is important in determining the need for repeat debridement(s). [GRADE -1; LEVEL OF EVIDENCE -B]

This guideline assumes that an individual with adequate experience should carry out surgical debridement, which is superior, but if not available, hydrosurgical [GRADE -2; LEVEL OF EVIDENCE –B] or enzymatic debridement [GRADE - 2; LEVEL OF EVIDENCE - C] should be performed.

Guideline 4.14: Topical Dressing Selection

We suggest applying a topical dressing that will manage venous leg ulcer exudate and maintain a moist, warm wound bed. [GRADE -2; LEVEL OF EVIDENCE -C]

We suggest selection of a primary wound dressing that will absorb wound exudate produced by the ulcer (alginates, foams) and protect the peri-ulcer skin. [GRADE -2; LEVEL OF EVIDENCE -B]

The condition of the venous ulcer bed may change over the course of treatment, which often necessitates selection of a different dressing type. Since many VLUs produce copious drainage that can be deleterious to wound healing, the fluid must be effectively removed. Alginate and foams effectively absorb this wound fluid and detritus, while a dry VLU dictates a hydrocolloid dressing to provide a warm, moist environment conducive to promoting wound healing.

Operative/Endovascular management

The development of newer endovascular techniques, such as endovenous ablation (EVA), angioplasty and stenting of the outflow track, had received little attention in previous VLU guidelines. Unfortunately, there is weak supporting evidence other than the large ESCHAR randomized controlled trial for the surgical treatment of the saphenous vein—only large observational case series are available supporting iliac angioplasty and stenting. The dedicated systematic review and meta-analysis performed by the Mayo Clinic Knowledge and Encounter research Unit identified only seven unique RCTs and four observational studies. They concluded that current evidence fails to conclusively support surgical or endovascular techniques for the healing of venous ulcers, but does endorse the treatment of superficial venous incompetence to prevent recurrence. Thus, the Venous Ulcer Venous Guidelines Writing Committee relied on expert opinion and the weight of observational studies to form their recommendations in some areas.

Guideline 6.1 Superficial Venous Reflux and Active Venous Leg Ulcer – Ulcer Healing

In a patient with a venous leg ulcer (C6) and incompetent superficial veins that have axial reflux directed to the bed of the ulcer, we suggest ablation of the incompetent veins in conjunction with standard compressive therapy to improve ulcer healing. [GRADE -2; LEVEL OF EVIDENCE -C]

Guideline 6.2 Superficial Venous Reflux and Active Venous Leg Ulcer – Prevent Recurrence

In a patient with a venous leg ulcer (C6) and incompetent superficial veins that have axial reflux directed to the bed of the ulcer, we recommend ablation of the incompetent veins and standard compressive therapy to prevent recurrence. [GRADE -1; LEVEL OF EVIDENCE-B]

Guideline 6.4: Superficial Venous Reflux with Skin Changes at Risk for Venous Leg Ulcer (C4b)

In a patient with skin changes at risk for venous leg ulcer (C4b) and incompetent superficial veins that have axial reflux directed to the bed of the affected skin, we suggest ablation of the incompetent superficial veins in addition to standard compressive therapy to prevent ulceration. [GRADE -2; LEVEL OF EVIDENCE –C]

The Mayo-dedicated systematic review and meta-analysis did not demonstrate a statistical advantage for superficial ablation and compression versus compression alone for ulcer healing, but an outpatient endovenous saphenous ablation under local/tumescent anesthesia alters the risk profile and improves the harm to benefit ratio in favor of treatment.5 Although saphenous ablation is performed on C6 limbs ostensibly to prevent recurrence, the potential benefit of improving time to healing in a slow-to-heal ulcer is an added benefit. The evidence for the benefits of EVA and compression for lowering recurrence rates is an extrapolation of RCTs, which compared open ligation and stripping with compression to compression alone, such as the ESCHAR trial. Comparative trials of EVA to L&S showed no difference between the two techniques with regard to efficacy.

Guideline 6.5: Combined Superficial / Perforator Venous Reflux With or Without Deep Venous Reflux and Active Venous Leg Ulcer

In a patient with a venous leg ulcer (C6) and incompetent superficial veins that have reflux to the ulcer bed, in addition to pathologic perforating veins (outward flow of >500 msec duration, with a diameter of >3.5mm) located beneath or associated with the ulcer bed, we suggest ablation of both the incompetent superficial veins and perforator veins, as well as standard compressive therapy to aid in ulcer healing and prevent recurrence. [GRADE -2; LEVEL OF EVIDENCE -C]

Guideline 6.6: Combined Superficial and Perforator Venous Reflux With or Without Deep Venous Disease and Skin Changes at Risk for Venous Leg Ulcer (C4b) or Healed Venous Ulcer (C5)

In a patient with skin changes at risk for venous leg ulcer (C4b), or healed venous ulcer (C5) and incompetent superficial veins that have reflux to the ulcer bed in addition to pathologic perforating veins (outward flow of >500 msec duration, with a diameter of >3.5mm) located beneath or associated with the healed ulcer bed, we suggest ablation of the incompetent superficial veins to prevent the development or recurrence of a venous leg ulcer. [GRADE -2; LEVEL OF EVIDENCE -C]

Treatment of the incompetent perforating veins can be performed simultaneously with correction of axial reflux, or can be staged with re-evaluation of perforator veins for persistent incompetence after correction of axial reflux.

Guideline 6.8: Treatment Alternatives for Pathologic Perforator Veins

For those patients who would benefit from pathologic perforator vein ablation, we recommend treatment by percutaneous techniques that include ultrasound-guided sclerotherapy or endovenous thermal ablation (radiofrequency laser) over open venous perforator surgery to eliminate the need for incisions in areas of compromised skin. [GRADE -1; LEVEL OF EVIDENCE -C]

The evidence for ablation of ICPVs is clouded by the concomitant treatment of the great saphenous vein in 50% of the subjects in the surgery/compression arm of the Dutch SEPS Trial.6 The important qualifier of a “pathologic ICPV” is defined by an outward flow of >500 msec duration, with a diameter of >3.5mm, which should limit the type of perforator that can be treated. An analysis of subsets in the Dutch SEPS Trial showed advantages for a longer ulcer-free period following ICPV ablation in patients with a medial based ulcer, recurrent ulcer and when done in specialized high volume centers.

The technical demands of SEPS, as illustrated in the volume-dependent results in the Dutch SEPS Trial, along with the high proportion of “missed perforators” in that trial—over 50% had at least one missed perforator— emphasizes the advantages of the direct percutaneous techniques. Now with ultrasound-guided sclerotherapy or thermal ablation, this procedure can be done under local anesthesia, as emphasized in the guideline above.

Guideline 6.14: Proximal Chronic Total Venous Occlusion / Severe Stenosis with Skin Changes at Risk for Venous Leg Ulcer (C4b), Healed (C5) or Active (C6) Venous Leg Ulcer - Endovascular Repair

In a patient with inferior vena cava and/or iliac vein chronic total occlusion or severe stenosis, with or without lower extremity deep venous reflux disease, which is associated with skin changes at risk for venous leg ulcer (C4b), healed venous leg ulcer (C5) or active venous leg ulcer (C6), we recommend venous angioplasty and stent recanalization in addition to standard compression therapy to aid in venous ulcer healing and to prevent recurrence. [GRADE -1; LEVEL OF EVIDENCE -C]

The strength of the recommendation for angioplasty and stenting (GRADE 1), in the face of lower quality evidence (C), is related to the large number of case series that showed benefit, as well as the opinion of the expert panel. There is increasing recognition of obstruction—either post-thrombotic or compression—as a cause of advanced chronic venous disease, and a percutaneous solution with an excellent patency favors this approach when possible.⁷

What makes the SVS/AVF VLU Guidelines unique?

To answer this question for a presentation at the Veith Meeting, I recently compared the new SVS/AVF VLU guidelines to VLU guidelines published after our previous systematic review and meta-analyses. As shown in the figure below, there are two new sets of VLU guidelines [Wound Healing Society and the American Heart Association’s Post- Thrombotic Syndrome Scientific Statement, which contained a section on venous ulcer] and three revisions of previously published guidelines [Care of people with chronic leg ulcers Royal New Zealand College of General Practitioners [1999] >Oct. 2011; Association for the Advancement of Wound Care [2005] >March 2012; and Scottish Intercollegiate Guidelines Network (SIGN) [2009] >August 2010].

This review identified several features where the SVS/ AVF appear unique. Both the size and breadth of the writing committee for the SVS/AVF guidelines, as well as the document’s adherence to the GRADE format, which is used in the ACCP guidlenes are defining features. The primary target audience of our guidelines is specialists— surgeons, phlebologists, interventional radiologists and wound care specialists—in contrast to general practioners or wound care nurses, as may be the primary target in other VLU guidelines. In the latter guidelines, which comprise 80%, this factor drives the content of many guidelines, so that many focus on when to refer patients for intervention, such as in the SIGN guidelines, rather than the specifics of surgical/endovascular treatment.

Both the American Heart Association and the Wound Healing Society guidelines, however, present recommendations for intervention, but are less comprehensive. The Wound Healing Society’s wording of recommendations on interventions appear quite similar to the SVS/AVF guidelines, but do not provide the detailed analysis of the surgical/endovascular management of venous ulcer found in the SVS/AVF guidelines, which are also supported by the concomitant-dedicated systematic review and meta-analysis. Finally, the SVS/AVF guidelines are intersocietal with prepublication endorsement by the American College of Phlebology and the Union Internationale de Phlebologie, as well as recently by the American College of Wound Healing and Tissue Repair.

The committee recognizes several important factors, including the need for widespread implimentation of the guidelines, monitoring the quality of and use of the guidelines and finally their impact on the incidence of VLU. The guidelines should be “living documents” that can be readily updated, when new compelling evidence is developed.

References

1. O’Donnell TF, Passman M (editors) Clinical practice guidelines of the Society for Vascular Surgery (SVS) and the American Venous Forum (AVF): Management of venous leg ulcers. J Vasc Surg. 2014; 60: 1S-90S.

2. O’Donnell T.F., Balk E. M. The need for an Intersociety Consensus Guideline for venous ulcer. J Vasc Surg 2011;54: 83S-90S.

3. Guyatt G, Gutterman D, Baumann MH, Addrizzo- Harris D, Hylek EM, Phillips B, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force. Chest 2006;129:174-81.)

4. Mauck KF, Asi N, Elraiyah TA, Undavalli C, Nabhan M, Altayar O, Sonbol B, Prokop LJ, Murad MH. Comparative systematic review and meta-analysis of compression modalities for the promotion of venous ulcer healing and reducing ulcer recurrence. J Vasc Surg 2014;

5. Mauck KF, Asi N, Undavalli C, Elraiyah TA, Nabhan M, Altavar O, Sonbol B, Prokop LJ, Murad MH. Sytematic review and meta-analysis of surgical interventions versus conservative therapy from venous ulcers. J Vasc Surg 2014;

6. van Gent WB, Hop WC, van Praag MC, Mackaay AJ, de Boer EM, Wittens CH.Conservative versus surgical treatment of venous leg ulcers: a prospective,randomized, multicenter trial. J Vasc Surg 2006;44(3):563-571.

7. Neglen P, Thrasher TL, Raju S. Venous outflow obstruction: An underestimated contributor to chronic venous disease. J Vasc Surg 2003; 38: 879-885