Review of the literature supporting international clinical practice guidelines on iliac venous stenting and their applicability to Australia and New Zealand practice

Abstract

Background

The overall goal of this report is to provide a high-level, practical approach to managing venous outflow obstruction (VOO).

Methods

A group of vascular surgeons from Australia and New Zealand with specific interest, training, and experience in the management of VOO were surveyed to assess current local practices. The results were analyzed and areas of disagreement identified. After this, the group performed a literature review of consensus guidelines published by leading international organizations focused on the management of chronic venous disease, namely, the Society for Vascular Surgery, American Venous Forum, European Society for Vascular Surgery, American Vein and Lymphatic Society, Cardiovascular and Interventional Radiology Society of Europe, and American Heart Association. These guidelines were compared against the consensus statements obtained through the surveys to determine how they relate to Australian and New Zealand practice. In addition, selected key studies, reviews, and meta-analyses on venous stenting were discussed and added to the document. A selection of statements with >75% agreement was voted on, and barriers to the guideline's applicability were identified. The final recommendations were further reviewed and endorsed by another group of venous experts.

Results

The document addresses two key areas: patient selection and technical aspects of venous stenting. Regarding patient selection, patients with clinically relevant VOO, a Clinical-Etiologic-Anatomic-Physiologic score of ≥3 or a Venous Clinical Severity Score for pain of ≥2, or both, including venous claudication, with evidence of >50% stenosis should be considered for venous stenting (Level of Recommendation Ib). Patients with chronic pelvic pain, deep dyspareunia, postcoital pain affecting their quality of life, when other causes have been ruled out, should also be considered for venous stenting (Level of Recommendation Ic). Asymptomatic patients should not be offered venous stenting (Level of Recommendation IIIc). Patients undergoing thrombus removal for acute iliofemoral deep vein thrombosis, in whom a culprit stenotic lesion of >50% has been uncovered, should be considered for venous stenting (Level of Recommendation Ib).

Conclusions

Patients with VOO have been underdiagnosed and undertreated for decades; however, in recent years, interest from physicians and industry has grown substantially. International guidelines aimed at developing standards of care to avoid undertreating and overtreating patients are applicable to Australia and New Zealand practice and will serve as an educational platform for future developments.

A group of vascular surgeons from Australia and New Zealand with specific interest, training, and experience in the management of venous outflow obstruction (VOO) of the abdominopelvic veins decided to review the literature supporting clinical management guidelines on venous stenting and their applicability to the particulars of the region with the aim of developing standards of care that could serve as an educational platform for future developments.

The overall goal of our report is to provide a high-level, practical approach to managing VOO of the femoroiliocaval veins. These guidelines are based on scientific evidence reviewed by experts in the field who also provided their opinions. In the present review, we refer to consensus guidelines published by leading international organizations focused on management of chronic venous disease, namely, the Society for Vascular Surgery (SVS), American Venous Forum (AVF), European Society for Vascular Surgery (ESVS), American Vein and Lymphatic Society, Cardiovascular and Interventional Radiology Society of Europe, and American Heart Association.1, 2, 3, 4, 5, 6, 7, 8, 9 In addition, we reference selected key reports and developments in the field that have helped in the establishment of these guidelines or occurred in the years after their publication. We also refer to recent reviews and meta-analyses.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 In the interest of time and space, we focus on and provide information that we believe is fundamental and helpful to physicians and surgeons managing VOO. We encourage readers in search of further information to access the very comprehensive source documents directly. By summarizing and evaluating the available evidence in the field, recommendations on the treatment of patients with VOO of the abdominopelvic veins in Australia and New Zealand have been formulated. Guidelines have the purpose of promoting a standard of care according to specialists in the field, in this case represented by vascular surgeons from the region. Under no circumstance should this guideline be seen as the legal standard of care for all patients, because the care provided to a single patient should always depend on individual patient characteristics, symptom variability, comorbidities, patient age, level of activity, patient expectations and the treatment setting, techniques available, physician expertise, and other factors. The recommendations are valid only at the time of publication. Because technology and disease knowledge in this field are evolving rapidly, the recommendations can become outdated. It is the aim of the authors to revise the guidelines when important new insights in the evaluation and management of VOO become available.

Methods

An initial search of the English literature was performed to identify guidelines on the management of chronic venous disease with a specific focus on VOO of the femoroiliocaval veins (as noted elsewhere in this article). Another search was conducted to identify reviews and meta-analyses of deep venous stenting in the past 20 years. Authors were asked to refer to these guidelines and reviews, their source documents, and other significant reports or interval developments related to current clinical practice. A Survey Monkey series was developed to identify areas of agreement and disagreement in current practice between the Australasian experts. The questionnaires encompassed common clinical decision-making scenarios and technical aspects of deep venous stenting. The results of the surveys were analyzed, and the results discussed within the group. All of us reviewed the literature independently before meeting to compare them against each other and against the results of the surveys. Through an ongoing iterative process, all the members edited and condensed the work into the final document. After robust discussion, only recommendations that achieved >75% consensus were included in the guidelines. The consensus document was drafted and potential barriers in current local practice identified. Finally, the document was reviewed and endorsed by another group of local and international experts. These recommendations discuss two key issues: patient selection and the technical aspects of venous stenting. Expert opinion and references to existing guidelines are summarized in our report. The grading systems originally established by the other guidelines were considered, and additional supporting evidence identified in our review was included. All treatment recommendations are in accordance with the Grading of Recommendations, Assessment, Development, and Evaluation method.²¹ This approach has been outlined in previous SVS guideline documents and includes two components. The first component is to determine the quality of the evidence underlying the recommendation (A, high; B, moderate; C, low to very low), and the second is to determine the strength of the recommendation (1, strong; 2, weak).

Venous disease is common in the general population and carries a significant socioeconomic, physical, and psychological burden, comparable with other chronic conditions (eg, diabetes, chronic pulmonary obstructive disease, arthritis), consuming 2% to 3% of health care funding.22, 23, 24 Because of the high morbidity associated with venous disease and the effects on the patient's quality of life (QOL), an effective treatment is a necessity.²⁵ Chronic venous disease manifests as a spectrum of conditions ranging from varicose veins, leg edema, recurrent cellulitis, lipodermatosclerosis, and, eventually, venous ulceration, all characterized by retrograde pressurization of the venous system. The pathophysiology of venous hypertension is attributable to calf pump failure, valvular incompetence, VOO, or a combination of these factors.²⁶ The critical role of venous disorders of the abdomen and pelvis has become increasingly recognized during the past two decades.26, 27, 28, 29, 30, 31, 32, 33 The Clinical-Etiologic-Anatomic-Physiologic (CEAP) classification was last revised in 2020 and has become the international standard.³⁴ However, it fails to capture clinical presentations caused by pelvic VOO, including chronic pelvic pain and venous claudication, as well as symptomatic lower extremity varicosities in either atypical (vulva or testicles, medial and posterior thigh, sciatic nerve) or typical saphenous distributions, with the latter frequently recurring after the initial treatment.^31,35,36 The new Symptom Varices Pathophysiology classification has been recently published with the aim of aiding clinicians with communication and definition of homogeneous patient populations.³¹ When used in combination with the CEAP classification, it can better define these patient groups and assist in decision-making and critical evaluation of outcomes.

VOO

Anatomic obstruction in the abdominopelvic veins can be caused by intraluminal post-thrombotic changes after an episode of deep vein thrombosis (DVT) or because of external venous compression (most commonly by the iliac arteries), eventually resulting in fibrotic stenosis. The role that venous obstruction plays in the development and progression of venous disease has been recognized for three decades26, 27, 28, 29, 30^,32,33; however, treatment options were limited to open surgery. Consequently, many patients with symptomatic chronic venous disease went untreated, resulting in significant morbidity and a decrease in QOL within that population.³⁷ With the beginning of the endovascular era in the early 1990s, the treatment paradigm shifted, and venous stenting became the standard of care for patients with clinically significant deep venous obstructive disease advocated by numerous societal guidelines.2, 3, 4, 5^,7, 8, 9^,38,39

Literature review

History of venous stenting

The first studies of venous stenting in the pelvic veins were reported in the early 1990s.40, 41, 42, 43, 44 In 2000, a large study by Neglén et al⁴⁵ reported the use of endovascular techniques for the treatment of primary and secondary iliac vein obstruction with minimal complications and excellent symptom resolution. Multiple studies followed, reporting high technical success, low complication rates, and excellent long-term patency (Table I).46, 47, 48, 49, 50 As experience increased, reviews of the literature yielded comparable results and a consistent message. Mussa et al⁵¹ in 2007 concluded that “endovenous stenting is the current method of choice in the treatment of chronic venous obstruction.” A landmark summary of peer-reviewed publications encompassing data from 1500 patients by Raju⁵² in 2013 concluded that, “Iliac vein stenting is safe, with negligible morbidity (<1%), patency rates of 90% to 100% for nonthrombotic disease and 74% to 89% for post-thrombotic disease at 3 to 5 years.” Another systematic review by Razavi et al⁵³ in 2015 of 2869 patients concluded that stent placement for iliofemoral VOO results in high technical success and acceptable complication rates, regardless of the cause of obstruction. As compelling evidence has continued to increase worldwide, international guidelines were published supporting venous stenting as a management option almost 20 years after the first report.

Table I.

Studies that have published long term follow up of deep venous stenting

Author	Year of publication	No. of patients	Long-term follow-up	Type of lesions	Patency—nonthrombotic lesions	Patency—thrombotic lesions	Conclusion
Neglen et al46	2007	982	9 years	Thrombotic and nonthrombotic	79% primary 100% assisted 100% secondary	57% primary 80% assisted 86% secondary	Low morbidity, no mortality, long-term high patency rate, the beneficial clinical outcome occurred regardless of reflux
Oguzkurt et al47	2008	36	4 years	Thrombotic	N/A	80% primary N/A 84% secondary	High technical success rate and good long-term patency
Hartung et al48	2009	89	12 years	Thrombotic and nonthrombotic	Not stated separately 83% primary 89% assisted 93% secondary		Safe, effective good long-term patency rates
Qing-You Meng et al49	2011	231	10 years	Nonthrombotic	91.7% primary N/A 94% secondary	N/A	Effective with good long term patency rates, varicose veins were alleviated in 98.7% of the patients
Kaichuang Ye50	2012	205	10 years	Nonthrombotic	98.7% primary 100% assisted N/A	N/A	Effective, safe, and durable. NIVL is a significant risk for recurrence after varicose veins treatment

N/A, Not available; NIVL, nonthrombotic iliac vein lesion.

In 2009, the AVF published guideline 4.17.0 with a grade 1 recommendation for endovenous stenting to improve the symptoms and QOL for patients with chronic iliofemoral obstruction and the grade of evidence was rated A (high quality).⁵ In 2014, the Cardiovascular and Interventional Radiology Society of Europe concluded that,

Stenting in chronic iliocaval obstruction is safe and effective. It provides excellent long-term results with respect to target vessel revascularization as well as symptom relief, therefore improving the QOL. In selected patients, it even reverses established post thrombotic syndrome (PTS). During the past decade, VOO has become recognized as more relevant in chronic venous disease than previously, and endovascular correction of outflow obstructions should be liberally indicated.³

In 2015, the ESVS guidelines gave a IIa/IIb recommendation toward considering balloon angioplasty and stenting for clinically relevant iliocaval or iliofemoral obstructive lesions of thrombotic or nonthrombotic origin.⁸ In addition, other societal guidelines are supportive of the use of balloon angioplasty and stenting for symptomatic venous obstruction^1,2,4,7 (Table II).

Table II.

Societal guidelines supporting balloon angioplasty and stenting for clinically relevant iliocaval or iliofemoral obstructive lesions

Society	Year
Society of Interventional Radiology Quality Improvement Guidelines7	2006
AVF5	2009
American Heart Association Scientific Statement1	2011
SVS and AVF4	2012
American Heart Association Scientific Statement2	2014
Cardiovascular and Interventional Radiology Society of Europe3	2014
SVS and the AVF for management of venous leg ulcers6	2014
WSVS8	2015
American Venous and Lymphatic Society (previously American College of Phlebology)9	2015
AVF, SVS, American Venous and Lymphatic Society, and Society of Interventional Radiology39	2020
ESVS38	2022

AVF, American Venous Forum; ESV, European Society of Vascular Surgery; SVS, Society for Vascular Surgery.

O'Donnell et al⁶ reported the 2014 clinical practice guidelines of the SVS and AVF for the management of venous leg ulcers. That extensive review recommends balloon angioplasty and stenting of obstructed iliofemoral venous outflow for patients with venous leg ulcers.⁶ The American Venous and Lymphatic Society (previously the American College of Phlebology) also has strong recommendations for balloon angioplasty and stenting for symptomatic outflow vein obstruction.⁹

Results

Initially, large caliber arterial stents or, more often, the Wallstent endo-prosthesis (Boston Scientific Corp, Marlborough, MA) were used to treat venous obstruction. The short-, mid-, and long-term outcomes reported throughout the previous 25 years have been very encouraging. In a study of 3468 initial iliocaval stents placed over an 18-year period, no significant adverse events or mortality occurred, and the stent occlusion rate was 3%. Stent occlusions occurred at a median follow-up of 5.8 months after placement, and 77% of the cases had occurred in post-thrombotic limbs, indicating a <1% risk of occlusion for nonthrombotic cases.⁵⁴

Despite the encouraging results with the braided Elgiloy endoprosthesis (Wallstent), some disadvantages were identified, including deployment inaccuracy, fore-shortening of both ends during ballooning, an inadequate radial force to allow for stent compression, in-stent restenosis at sites with overlapping stents such as the external iliac vein/common iliac vein transition where two stents are often connected and stressed during hip flexion, and contralateral iliac vein jailing at the iliocaval confluence. Thus, self-expanding nitinol stent designs started entering the market in the early 2000s.

The technique evolved over time, and actually, the radial resistive force of the fixated Wallstent is actually better than some of the dedicated venous stents, including the Zilver Vena (Cook Medical Inc, Bloomington, IN), Vici (Boston Scientific), and Sinus XL Flex (OptiMed, Baden-Wurttemberg, Germany) stents, according to an experimental study comparing venous stents by Dabir et al.⁵⁵ Also, the crush resistance of the Wallstent is particularly good. It is the chronic outward force that is the issue. In Australia, the Therapeutic Goods Administration approval for dedicated venous stents was obtained, on average, 12 months after European approval (Table III). In Australia and New Zealand, interventional radiologists have traditionally dominated venous stenting. However, since the introduction of dedicated venous stents, interest from vascular surgeons has grown steadily. An Australian report of 109 patients treated by a vascular surgeon between 2011 and 2017 reported that >95% of the stents were dedicated venous stents (Zilver Vena; Cook Medical Inc), sinus Venous, Sinus XL (OptiMed).⁵⁶

Table III.

TGA approvals of dedicated venous stents

Dedicated venous stent	TGA approval date
Zilver Vena (Cook Medical)	2011
Sinus-Venous and Sinus XL (Optimed Medizinische Instrumente GmbH)	2012
Vici (Boston Scientific Corporation)	2014
Venovo (BD Interventional)	2016
Abre (Medtronic)	2019

TGA, Therapeutic Goods Administration.

New devices have continued to enter the global market, such as Blueflow (Plus Medica GmbH & Co KG, Düsseldorf, Germany), approved for use in Europe since 2018, but not yet available in Australia and New Zealand, and the Beyond (Bentley Global, Duluth, GA) currently only available to venous experts. As experience and knowledge expands at a rapid pace, reviews of venous stents^{10,12,13,16,20} are available, as are up to-date management guidelines1, 2, 3, 4, 5, 6, 7, 8, 9 and appropriate use criteria.³⁹

Dedicated and nondedicated venous stent trial results

Reviews of dedicated and nondedicated venous stents have been reported in the past few years. The results have been consistent, regardless of the stents used. The predominant feature affecting long-term patency is related to the pathology treated, with superior long-term results for patients treated for nonthrombotic disease. The long-term patency of stents deployed after acute DVT seem to be similar to the patency of nonthrombotic cases and far superior to the post-thrombotic cases.¹³ Several reviews of stents, including dedicated and nondedicated venous stents, showing comparable results are presented in Table IV. A low complication rate of 0.8% to 7.4% was reported, even when including complications not related to the stents, but to adjunctive procedures such as endovenectomy or arteriovenous fistulas in complex hybrid operations or complications from thrombus removal techniques in acute DVT. The patency rates were consistent with previous reports of 89% to 100% for nonthrombotic lesions and 64% to 96% for thrombotic lesions. A study by Powell et al⁵⁷ showed that the results with the Bard Venovo (C. R. Bard, Inc., Murray Hill, NJ) venous stent were comparable with those with the composite Wallstent-Z stent configuration for clinical outcomes, QOL improvement, and stent patency.

Table IV.

Reviews of venous stents

Author	No. of patients	No. of dedicated venous stents	Complication rate	Primary patency rate (nonthrombotic)	Primary patency rate (thrombotic)	Conclusion
Seager, 201612	4959	Not reported (minority)	0-8.7%	Not stated separately (32% to 98.7%)		Safe and effective
Williams, 202010	3812	740	<1%	96%	73%	Safe and effective
Rodrigues, 202113	1050	Not reported	7.4% (includes clot removal treatment complications)	94.6%	84.1%	Safe and effective
Badesha,. 202220	1688	1688	4.5% (includes bleeding with hybrid intervention)	89%-99%	64%-96%	Safe and effective
Majeed, 202216	5154	Not reported	5.5% (bleeding)	96%-100%	77%-94%	Safe and effective

Complications

The procedure has been deemed safe and effective for >25 years. However, the voluntary recall of the Vici and Venovo stents from the market raised some questions regarding concerns of migration and maldeployment. The Venovo stent has returned to the market. Series of individual dedicated venous stents, including trial results, have reported excellent outcomes (Table V).^11,14,15,17, 18, 19

Table V.

Results of dedicated venous stents

Author	No. of patients	Stent name and brand	Complication rate	Primary patency rate non thrombotic	Primary patency rate thrombotic	Conclusion
De wolf, 201517	75	Sinus-venous -Optimed	5% (minor bleeding)	100%	85%	Low morbidity, no mortality, good patency rates
Van Vuuren, 201811	200	Sinus-venous -Optimed	1%	92%	71%	Loss of stent patency due to stent-related issues like kinking or tapering is hardly ever seen
Black, 201819	88 (includes only occluded vessels)	Vici -Boston Scientific	2% major (spinal bleed and stent malposition) 3% stent fracture	N/A	59%	Good secondary patency rate and durable and substantial symptomatic resolution in patients with chronic post-thrombotic occlusions, regardless of whether stents extended beneath the inguinal ligament
Razavi, 201814	30	Vici -Boston Scientific	3% (access site)	100%	93%	Safe and feasible for treatment of symptomatic iliofemoral venous obstruction, with excellent 12-month patency rates and significant improvement seen in clinical symptoms and QOL indices.
Dake, 202118	170	Venovo- Bard	6.5% (includes target vessel revascularization, DVT and PE, there were no migrations, no fractures, no mortality)	98.6%	87.6%	At 3 years, primary patency was 84%, reintervention rates were low, standardized quality-of-life and pain measures improved from baseline, and there was no stent migration or fractures
Murphy, 202215	200	Abre- Medtronic	2% (there were no migrations, no fractures, no mortality)	98.6%	79.8%	A high patency rate with a good safety profile. Patients demonstrated a significant reduction in clinical symptoms and improvement in QOL that was maintained through 12-month follow-up

DVT, Deep vein thrombosis; N/A, not available; PE, pulmonary embolism; QOL, quality of life.

Migration

A recent review by Sayed et al⁵⁸ of all migrated stent reports from 1994 to 2020 from all locations found 54 events. None of the studies had reported the migration of stents >100 mm long with only three >14 mm in diameter. Only 26 had originally been intended for the iliocaval segment. The investigators suggested this is an underreported complication; however, simultaneously, they reported that, in the >2000 stent cases they had performed, they had never experienced one and suggested that physician education was mandatory to avoid it. Another review by Badesha et al⁵⁹ found an incidence of 0.17% when analyzing series with ≥50% of dedicated venous stents. Strategies to mitigate or avoid the risk altogether have been reported, including patient selection, the use of intravascular ultrasound (IVUS) examination to establish whether the lesion is static or dynamic, sizing with measurements performed under Valsalva maneuver, and identification of adequate landing zones. The authors commented on the higher risk with closed cell designs vs open cell designs, although the numbers were too small for any meaningful statistical analysis. A postmarket registry and adequate physician training were strongly recommended.

Fracture

Stent fractures have been described when stents have been deployed below the inguinal ligament. However, in contrast with widespread belief, the common femoral vein will not be compressed by the inguinal ligament during hip flexion, but rather by the pubis during hip extension, at about 1 cm below the inguinal ligament.⁶⁰ A recent comparison of open vs closed cell nitinol stents by Morris et al⁶¹ suggested it to be significantly less common with open cell stents than with closed cell stents. However, it is unclear whether fractures have any clinical effects.

Patency loss

Stent occlusion can be caused by acute thrombosis or, less commonly, by progressive in-stent stenosis. It is yet unclear whether in-stent stenosis can be prevented. However, an Australian report on the material removed from an occluded stent using directional atherectomy revealed patterns of cellular components similar to arterial in-stent stenosis.⁶² A large study of 254 poststent venograms with biopsies of in-stent contents demonstrated the coexistence of thrombus and diffuse intimal thickening, suggesting that the evolution of human venous in-stent restenosis seems to follow a time-dependent course from fresh and organizing thrombus to diffuse intimal thickening, which might explain, in part, why many of these lesions might not respond to thrombolytic or anticoagulant treatment alone.⁶³ The patency rates have been exceedingly good in nonthrombotic limbs, >90% in all large reported series and reviews of the previous 25 years.^{10,12,13,16,20} Post-thrombotic limbs have a higher incidence of in-stent stenosis or occlusion. Several factors have been identified as the reasons for patency loss, including inflow vessel quality, lack of identification and treatment of all lesions, and suboptimal anticoagulation. Balloon angioplasty or adjunctive open surgical procedures, such as endovenectomy to improve the quality of the inflow vessels have been described.^64,65 The routine use of IVUS examination has been strongly recommended to avoid missing lesions. A recent report by Tran et al⁶⁶ has demonstrated improved midterm patency outcomes when using IVUS. A multidisciplinary team with hematology involvement has also been suggested to improve outcomes.

Level of Evidence and future research

The current level of evidence is considered weak despite the multitude of reports and strong recommendations from medical societies that range from a Level of Evidence Ia in 2009 by the AVF to Level of Evidence of IIb in 2022 by the ESVS. This is likely to change when more randomized controlled trials (RCTs) are reported. An RCT by Rossi et al²⁸ presented at the AVF in 2015 and published in 2017 compared conservative management vs intervention for symptomatic outflow obstruction. They showed that venous stenting is safe and promotes effective relief of symptoms and improvement in QOL compared with medical treatment alone. Recently, Optimed announced two RCTs soon to be published, Stent vs Conservative Treatment in Patients with Deep Venous Obstruction (STEVECO) and Treatment of the Post Thrombotic Syndrome with the Oblique Stent (TOPOS).⁶⁷ The Chronic Venous Thrombosis: Relief with Adjunctive Catheter-directed Therapy (C-Tract) trial seems to be behind schedule with recruitment, but hopefully will contribute with meaningful data.⁶⁸ Prospective studies on topics such as the need for antiplatelet therapy, how to determine appropriate inflow, or how to prevent in-stent stenosis, are currently under development. However, large registries might become a more reliable source of high-quality data, as seen with the Swiss registry.⁶⁹

Patient selection

Patient selection is a concept in constant evolution, and multiple clinical scenarios are not captured in societal guidelines. However, the overall consistent message is that the indication to treat relates to clinically relevant outflow obstruction.1, 2, 3, 4, 5, 6, 7, 8, 9 Several noninvasive diagnostic modalities have been compared against the reference standard of IVUS examination, including transabdominal duplex ultrasound examination,⁷⁰ computed tomography venography,⁷¹ and magnetic resonance venography.⁷² The authors suggest transabdominal duplex ultrasound examination as the first-line imaging modality for patients presenting with features of advanced venous disease or severe symptoms suggestive of outflow obstruction, ideally complemented by axial imaging, depending on local expertise. Ultimately, the diagnosis should be confirmed with IVUS planimetry, because this measure is the only one that predicts clinical improvement after stenting, as demonstrated in the Venogram vs IVUS for Diagnosing IVO (VIDIO) trial.⁷³ In 2020, the AVF, in collaboration with the SVS, American Vein and Lymphatic Society, and Society of Interventional Radiology, stated that for symptomatic patients with CEAP classes 4 to 6 who have iliac vein or inferior vena cava obstructive disease, defined as >50% area reduction by IVUS examination or occlusion and no superficial truncal reflux, stenting as the first-line treatment is considered appropriate.³⁹ Similar recommendations can be found in the most recent update from the ESVS guidelines published in 2022, with a class where a Class IIa B recommendation is given to balloon angioplasty and stenting for severely symptomatic patients, active venous leg ulceration, and venous claudication.³⁸ Table VI.

Table VI.

Level of Recommendation of existing guidelines

GUIDELINE	Year	Sponsor	Clinical indication	Morphological indication	Strength of recommendation	Quality of evidence	Latest reference	Key questions	Specific systematic review	Emphasis 0N ASSESSMENT of QOL
AVF5	2009	Societal	Clinically relevant VOO	N/A	Strong (I)	High (A)	2008	Yes	Yes	YES
CIRSE3	2014	Societal	CEAP 3-6	N/A	Strong	N/A	2013	Yes	Yes	YES
AHA2	2014	Societal	Severe post-thrombotic syndrome	Occlusion	Moderate (IIa)	Low (C)	2014	Yes	Yes	YES
ESVS8	2015	Societal	Clinically relevant VOO	>50% stenosis	Moderate (IIa)	Moderate (B)	2014	Yes	Yes	YES
AVLS9	2015	Societal	Clinically relevant VOO Includes pelvic pain	N/A	Strong (I)	Moderate (B)	2015	Yes	Yes	YES
AVF/SVS/SIR39	2020	Multisocietal	Clinically relevant VOO CEAP 3-6 includes venous claudication	>50% area reduction	Strong	Moderate (B)	2019	Yes	Yes	YES
ESVS38	2022	Societal	Clinically relevant VOO CEAP 3-6 Includes venous claudication and pelvic pain	>50% stenosis	Moderate (IIa)	Moderate (B)	2021	Yes	Yes	YES

AHA, American Heart Association; AVF, American Venous Forum; AVLS, American Vein & Lymphatic Society; CEAP, Clinical-Etiologic-Anatomic-Physiologic; CIRSE, Cardiovascular and Interventional Radiological Society of Europe; ESVS, European Society for Vascular Surgery; N/A, not available; SIR, Society of Interventional Radiology; SVS, Society for Vascular Surgery; VOO, venous outflow obstruction.

The authors believe that consistency is needed in the assessment, indication for treatment, and evaluation of outcomes. Thus, a decision was made to adopt the wording from the baseline trial eligibility requirements used in the postmarket trials of three dedicated venous stents in the United States: VIRTUS (Vici; Boston Scientific),¹⁴ VERNACULAR (Venovo; Bard),¹⁸ and ABRE (Abre; Medtronic, Minneapolis, MN).¹⁵

A documented iliofemoral obstruction of ≥50% in the presence of a CEAP score of ≥3, a Venous Clinical Severity Score pain score of ≥2, or both. Because disabling venous claudication is common in post-thrombotic syndrome⁷⁴ and can be present even in the absence of advanced skin changes, the authors also included venous claudication in the recommendation. For patients with C3 only, with no significant pain, the authors recommend caution because edema tends to be multifactorial and the response to stenting in established phlebolymphedema is unpredictable³⁹ (Table VII). The concurrent presence of superficial axial reflux and iliocaval obstruction is common. The authors made a point that it remains unclear regarding whether stenting should be performed first or used subsequently or concomitantly with treatment of superficial disease. Deep venous obstruction can be the cause of secondary incompetence and stenting can eliminate the underlying cause of varicose veins and other manifestations of venous disease; however, the strategy of treating the superficial system first may be preferred because of fewer procedural risks and treating small, nondilated incompetent trunks is unlikely to provide any significant benefit to the patient. The panelists stressed the need for further research to understand the benefit of treating obstruction alone. This recommendation mirrors other societal guidelines.^38,39

Table VII.

Comparison of existing guidelines and their applicability to Australia and New Zealand

Management of deep VOO	Existing guidelines	References	Level of Recommendation	Applicability to Australia and New Zealand
Patients with clinically relevant VOO (CEAP score of ≥3, a VCSS pain score ≥2 or both, including venous claudication) and evidence of >50% stenosis should be considered for venous stenting	ESVS SVS AVLS AVF CIRSE AHA	2,3,5,9,38,39	IB	Yes
Patients undergoing thrombus removal treatment for acute iliofemoral DVT, in whom a culprit stenotic lesion of >50% has been uncovered, should be considered for venous stenting	ESVS SVS	38,39	IB	Yes
Patients with a stenosis of >50% and chronic pelvic pain, deep dyspareunia, postcoital pain affecting QOL, when other causes have been ruled out, should be considered for venous stenting	ESVS AVLS	9,38	IC	Yes
Asymptomatic patients should not be offered venous stenting	ESVS SVS	38,39	IIIC	YES

AHA, American Heart Association; AVF, American Venous Forum; AVLS, American Vein & Lymphatic Society; CEAP, Clinical-Etiologic-Anatomic-Physiologic; CIRSE, Cardiovascular and Interventional Radiological Society of Europe; DVT, deep vein thrombosis; ESVS, European Society for Vascular Surgery; QOL, quality of life; SVS, Society for Vascular Surgery; VCSS, Venous Clinical Severity Score; VOO, venous outflow obstruction.

In cases of symptomatic pelvic varices and pelvic obstruction, treatment was also recommended when other causes for pain have been excluded, because there seems to be a growing body of evidence in regard to the association of VOO and chronic pelvic pain in women^{15,35,36,75,76}; however, no Level of Recommendation was allocated for this clinical scenario in the ESVS guidelines,³⁸ although the AVLS gives it a Grade 1C.⁹

Regarding balloon angioplasty and stenting of asymptomatic patients, the authors agreed it was considered inappropriate because there is no long-term data evaluating benefit from stenting prophylactically.

Technical aspects

Several technical recommendations to increase safety and efficacy have been included as a practical guide in Table VIII.

Table VIII.

Technical recommendations to increase safety and efficacy

Technical aspects of deep venous stenting
Venoplasty alone is rarely sufficient; therefore, we recommend venous stenting to treat these lesions.77
We recommend venoplasty before stent placement up to the reference vessel or stent diameter.78
We recommend balloon dilatation of the stent to ensure stent expansion and proper wall apposition.3
When crossing a chronic occlusion, we recommend oblique or lateral views to ensure the wire is in the proper location anterior to the spine since inadvertent stenting into the obturator vein or spinal canal has been reported.79
To improve inflow vessel quality, we recommend balloon angioplasty and in select cases endovenectomy.80
We recommend IVUS guidance in all venous stenting procedures to enable accurate identification of lesion characteristics, stent sizing and assessment of landing zones and stent expansion.66
We recommend stents bigger than 12 mm and longer than 80 mm to minimize the risk of migration.58
We recommend anticoagulation in all venous stenting cases, duration to be determined by patient and lesion characteristics81
We recommend duplex assessment within 2-4 weeks after the procedure because stent thrombosis can be an early complication and subsequently, we recommend an ongoing surveillance protocol.79
We recommend antiplatelet therapy to be considered long term in patients undergoing venous stenting.81

IVUS, Intravascular ultrasound.

Barriers

The only barrier identified in these recommendations is the use of IVUS examination; in many places, including Australia, no Medicare rebate is available for its use.

Conclusions

Patients suffering from deep VOO have been underdiagnosed and undertreated for decades, but in recent years interest from physicians and industry has grown substantially. The advent of simpler and safer treatment options has revolutionized its management; unfortunately, formal training for venous disease has not grown at the same rate. International guidelines aimed at developing standards of care to avoid undertreating and overtreating patients are applicable to Australia and New Zealand practice and will serve as an educational platform for future developments.

Author Contributions

Conception and design: LV, IB, SB, PP, ST, RV, TV, RT

Analysis and interpretation: LV, IB, SB, PP, ST, RV, TV, RT

Data collection: LV, IB, SB, PP, ST, RV, TV, RT

Writing the article: LV, IB, SB, PP, ST, RV, TV, RT

Critical revision of the article: LV, IB, SB, PP, ST, RV, TV, RT

Final approval of the article: LV, IB, SB, PP, ST, RV, TV, RT

Statistical analysis: Not applicable

Obtained funding: Not applicable

Overall responsibility: LV

Disclosures

None.

Arjun Jayaraj, MD, SECTION EDITOR