Treatment of Varicose Veins/Venous Insufficiency

Transcription

1 MEDICAL POLICY Treatment of Varicose Veins/Venous Insufficiency BCBSA Ref. Policy: Effective Date: March 1, 2017 Last Revised: Jan. 23, 2018 Replaces: , , , and RELATED MEDICAL POLICIES: Cosmetic and Reconstructive Services Select a hyperlink below to be directed to that section. POLICY CRITERIA DOCUMENTATION REQUIREMENTS CODING RELATED INFORMATION EVIDENCE REVIEW REFERENCES HISTORY Clicking this icon returns you to the hyperlinks menu above. Introduction Varicose veins are swollen, twisted veins that are visible just below the skin. They most often occur in the legs but can develop in other parts of the body. Veins have valves that keep the blood moving toward the heart. If the valves are weak or damaged, blood can pool in the veins. It s this pooling that causes the veins to swell and appear twisted. Most varicose veins do not result in physical symptoms. On occasion, they can cause symptoms such as pain, an achy feeling, bleeding, or skin ulcers (sores). Varicose veins usually can be treated without surgery by activities such as exercising, raising the legs, or wearing compression stockings. This policy describes when varicose vein surgery or other procedures may be considered medically necessary. Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered. Policy Coverage Criteria

2 Documentation Requirements Review of this procedure requires the provider to specifically indicate the following in the clinical notes submitted with the request: The CPT codes for the procedures being requested AND The name of the vein to be treated with each CPT code Vein(s) Greater or lesser (small) saphenous veins Medical Necessity Treatment of the greater or lesser (small) saphenous veins by surgery (ligation and stripping), endovenous radiofrequency ablation, laser ablation or microfoam sclerotherapy (eg, Varithena) may be considered medically necessary for symptomatic varicose veins/venous insufficiency when the following criteria have been met: There is moderate to severe (greater than 0.5 second) saphenous reflux documented on venous studies and CEAP [Clinical-Etiology-Anatomy-Pathophysiology] class C2 or greater (see Definition of Terms) AND There is documentation of one or more of the following four indications: o Ulceration secondary to venous stasis OR o Recurrent superficial thrombophlebitis OR o Hemorrhage or recurrent bleeding episodes from a ruptured superficial varicosity OR o Persistent pain, swelling, itching, burning, or other symptoms are associated with saphenous reflux AND These symptoms significantly interfere with activities of daily living AND Page 2 of 41

3 Vein(s) Medical Necessity Conservative management, including compression therapy (see Definition of Terms) for at least 3 months, has not improved the symptoms Note: If compression therapy is successful, it should be continued for as long as it is working. Failure of conservative therapy is defined as pain, swelling, itching, burning, or other symptoms associated with vein reflux, despite conservative therapy, severe enough to require daily pain medicines and causing inability to manage daily activities at home or at work. Accessory saphenous veins Treatment of the greater or lesser (small) saphenous veins using the following techniques is considered investigational, including, but not limited to: Cyanoacrylate adhesive/cyanoacrylate embolization (CAE) (eg, VenaSeal System) Endovenous cryoablation Endovenous mechanochemical ablation (MCA) (eg, MOCA ClariVein) Stab avulsion Stab/Hook/Micro-phlebectomy Transilluminated powered phlebectomy (TIPP) (eg, TRIVEX System) Treatment of accessory saphenous veins by surgery (ligation and stripping), endovenous radiofrequency ablation, laser ablation or microfoam sclerotherapy may be considered medically necessary for symptomatic varicose veins/venous insufficiency when the following criteria have been met: The greater or lesser (small) saphenous veins have been previously eliminated (at least 3 months) when the greater or lesser (small) saphenous veins had reflux OR There is no reflux documented in both the greater and lesser (small) saphenous veins AND There is moderate to severe (greater than 0.5 second ) accessory saphenous reflux documented on venous studies AND Page 3 of 41

4 Vein(s) Medical Necessity There is documentation of one or more of the following 4 indications: o Ulceration secondary to venous stasis OR o Recurrent superficial thrombophlebitis OR o Hemorrhage or recurrent bleeding episodes from a ruptured superficial varicosity OR o Persistent pain, swelling, itching, burning, or other symptoms are associated with saphenous reflux AND These symptoms significantly interfere with activities of daily living AND Conservative management, including compression therapy (see Definition of Terms) for at least 3 months, has not improved these symptoms. Note: If compression therapy is successful, it should be continued for as long as it is working. Failure of conservative therapy is defined as pain, swelling, itching, burning, or other symptoms associated with vein reflux, despite conservative therapy, severe enough to require daily pain medicines and causing inability to manage daily activities at home or at work Treatment of accessory saphenous veins by surgery, endovenous radiofrequency, laser ablation, or microfoam sclerotherapy that does not meet the criteria described above is considered not medically necessary Treatment of the accessory saphenous veins using the following techniques is considered investigational, including, but not limited to: Cyanoacrylate adhesive/cyanoacrylate embolization (CAE) (eg, VenaSeal System) Endovenous cryoablation Endovenous mechanochemical ablation (MCA) (eg, MOCA Page 4 of 41

5 Vein(s) Symptomatic varicose tributaries Medical Necessity ClariVein) Stab avulsion Stab/Hook/Micro-phlebectomy Transilluminated powered phlebectomy (TIPP) (eg, TRIVEX System) The following treatments are considered medically necessary as a component of the treatment of symptomatic varicose tributaries when performed concurrently with or within 10 days of treatment (surgical, radiofrequency or laser) of the saphenous veins (none of these techniques has been shown to be superior to another): Sclerotherapy Stab avulsion Stab/Hook/Micro-phlebectomy Transilluminated powered phlebectomy (TIPP) (eg, TRIVEX System) When stab avulsion, hook phlebectomy, sclerotherapy, or transilluminated powered phlebectomy (TIPP) is requested more than 10 days following a prior surgical, radiofrequency or laser treatment, it may be considered medically necessary when there is documentation of one or more of the following 4 indications: Ulceration secondary to venous stasis OR Recurrent superficial thrombophlebitis OR Hemorrhage or recurrent bleeding episodes from a ruptured superficial varicosity OR Persistent pain, swelling, itching, burning, or other symptoms are associated with saphenous reflux AND o These symptoms significantly interfere with activities of daily living AND o Conservative management, including compression therapy Page 5 of 41

6 Vein(s) Medical Necessity (see Definition of Terms) for at least 3 months, has not improved these symptoms Note: If compression therapy is successful, it should be continued for as long as it is working. Failure of conservative therapy is defined as pain, swelling, itching, burning, or other symptoms associated with vein reflux, despite conservative therapy, severe enough to require daily pain medicines and causing inability to manage daily activities at home or at work Perforator veins Treatment of symptomatic varicose tributaries when performed either at the same time or following prior treatment of saphenous veins using any other techniques than noted above is considered investigational, including, but not limited to: Cyanoacrylate adhesive/cyanoacrylate embolization (CAE) (eg, VenaSeal System) Endovenous cryoablation Endovenous mechanochemical ablation (MCA) (eg, MOCA ClariVein) Endovenous radiofrequency or laser ablation Surgical ligation (including subfascial endoscopic perforator surgery) or endovenous radiofrequency or laser ablation of incompetent perforator veins may be considered medically necessary as a treatment of active or healed leg ulcers with documented persistent reflux when ALL of the following conditions have been met: The superficial saphenous veins (greater, lesser, or accessory saphenous and symptomatic varicose tributaries) have been previously eliminated AND Three months after superficial vein treatment and compression therapy (see Definition of Terms), the perforator veins have BOTH an outward flow of greater than or equal to 500 ms duration AND a diameter of greater than or equal to 3.5mm AND The perforator veins are located underneath healed or active ulcers Page 6 of 41

7 Vein(s) Medical Necessity AND The venous insufficiency is not secondary to deep venous thromboembolism Ligation or ablation of incompetent perforator veins performed concurrently with superficial venous surgery is not medically necessary. Telangiectasia Treatment of incompetent perforator veins using any other techniques than noted above is considered investigational, including, but not limited to: Cyanoacrylate adhesive/cyanoacrylate embolization (CAE) (eg, VenaSeal System) Endovenous mechanochemical ablation (MCA) (eg, MOCA ClariVein) Sclerotherapy Stab avulsion Stab/Hook/Micro-phlebectomy Transilluminated powered phlebectomy (TIPP) (eg, TRIVEX System) Treatment, by any method, of small telangiectasia such as spider veins (1mm or less), superficial reticular veins (1-2 mm), angiomata, and hemangiomata is considered cosmetic. Treatment Ultrasound guidance Coverage Criteria It should be noted that the bulk of the literature discussing the role of ultrasound guidance refers to sclerotherapy of the saphenous vein, as opposed to the varicose tributaries. When ultrasound guidance is used to guide sclerotherapy of the varicose tributaries, it would be considered either not medically necessary or incidental to the injection procedure. Documentation Requirements Written documentation in the medical record must include: 1. CPT codes for the procedures being requested, and the name of the vein to be treated with Page 7 of 41

8 Documentation Requirements each CPT code 2. Copy of the venous studies (ultrasound studies evaluating blood flow in the veins) 3. CEAP (Clinical-Etiology-Anatomy-Pathophysiology) class C2 or greater (Clinical classification, large varicose veins) 4. One or more indications: o Ulceration secondary to venous stasis (leg ulcers caused by poor blood flow in the veins) o Recurrent superficial thrombophlebitis (recurrent blood clots or inflammation in a small veins near the surface of the skin) o Hemorrhage or recurrent bleeding episodes from a ruptured superficial varicosity (bleeding from a varicose vein) o Persistent pain, swelling, itching, burning, or other symptoms are associated with saphenous reflux (pooling of the blood caused by valves that don t work correctly) AND These symptoms significantly interfere with activities of daily living Conservative management including compression therapy for at least 3 months has not improved the symptoms Coding Code Description CPT Injection of non-compounded foam sclerosant with ultrasound compression maneuvers to guide dispersion of the injectate, inclusive of all imaging guidance and monitoring; single incompetent extremity truncal vein (eg, great saphenous vein, accessory saphenous vein) (new code effective 1/1/18) Injection of non-compounded foam sclerosant with ultrasound compression maneuvers to guide dispersion of the injectate, inclusive of all imaging guidance and monitoring; multiple incompetent truncal veins (eg, great saphenous vein, accessory saphenous vein), same leg (new code effective 1/1/18) Single or multiple injections of sclerosing solutions, spider veins (telangiectasia); limb or trunk Injection of sclerosing solution; single vein Injection of sclerosing solution; multiple veins, same leg Endovenous ablation therapy of incompetent vein, extremity, inclusive of all imaging Page 8 of 41

9 Code Description guidance and monitoring, percutaneous, mechanochemical; first vein treated Endovenous ablation therapy of incompetent vein, extremity, inclusive of all imaging guidance and monitoring, percutaneous, mechanochemical; subsequent vein(s) treated in a single extremity, each through separate access sites (List separately in addition to code for primary procedure) Endovenous ablation therapy of incompetent vein, extremity, inclusive of all imaging guidance and monitoring, percutaneous, radiofrequency; first vein treated Endovenous ablation therapy of incompetent vein, extremity, inclusive of all imaging guidance and monitoring, percutaneous, radiofrequency; second and subsequent veins treated in a single extremity, each through separate access sites (List separately in addition to code for primary procedure) Endovenous ablation therapy of incompetent vein, extremity, inclusive of all imaging guidance and monitoring, percutaneous, laser; first vein treated Endovenous ablation therapy of incompetent vein, extremity, inclusive of all imaging guidance and monitoring, percutaneous, laser; second and subsequent veins treated in a single extremity, each through separate access sites (List separately in addition to code for primary procedure) Endovenous ablation therapy of incompetent vein, extremity, by transcatheter delivery of a chemical adhesive (eg, cyanoacrylate) remote from the access site, inclusive of all imaging guidance and monitoring, percutaneous; first vein treated (new code effective 1/1/18) Endovenous ablation therapy of incompetent vein, extremity, by transcatheter delivery of a chemical adhesive (eg, cyanoacrylate) remote from the access site, inclusive of all imaging guidance and monitoring, percutaneous; subsequent vein(s) treated in a single extremity, each through separate access sites (List separately in addition to code for primary procedure) (new code effective 1/1/18) Vascular endoscopy, surgical, with ligation of perforator veins, subfascial (SEPS) Ligation and division of long saphenous vein at saphenofemoral junction, or distal interruptions Ligation, division, and stripping, short saphenous vein Ligation, division, and stripping, long (greater) saphenous veins from saphenofemoral junction to knee or below Ligation and division and complete stripping of long and short saphenous veins with radical excision of ulcer and skin graft and/or interruption of communicating veins of lower leg, with excision of deep fascia Ligation of perforator veins, subfascial, radical (Linton type) including skin graft, when performed, open, 1 leg Page 9 of 41

10 Code Description Ligation of perforator vein(s), subfascial, open, including ultrasound guidance, when performed, 1 leg Stab phlebectomy of varicose veins, 1 extremity; stab incisions Stab phlebectomy of varicose veins, 1 extremity; more than 20 stab incisions Ligation and division of short saphenous vein at saphenopopliteal junction (separate procedure) Ligation, division, and/or excision of varicose vein cluster(s), one leg Unlisted procedure, vascular surgery (eg, MOCA ClariVein, Varithena, TRIVEX System) Note: CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). HCPCS codes, descriptions and materials are copyrighted by Centers for Medicare Services (CMS). Related Information Definition of Terms Accessory saphenous veins: Veins that travel in parallel with the greater and lesser saphenous veins and are generally 2 to 2.5 mm in their normal state. Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification: Considers the clinical, etiologic, anatomic, and pathologic (CEAP) characteristics of venous insufficiency. See table below. Class C0 C1 C2 C3 C4a C4b C5 C6 S Clinical Classification No visible or palpable signs of venous disease Telangiectasies or reticular veins Varicose veins Edema Pigmentation and eczema Lipodermatosclerosis and atrophie blanche Healed venous ulcer Active venous ulcer Symptoms including ache, pain, tightness, skin irritation, heaviness, muscle cramps, and other Page 10 of 41

11 Class A C0 Clinical Classification complaints attributable to venous dysfunction Asymptomatic No visible or palpable signs of venous disease Compression Therapy: Compression hosiery or stockings are often the first line of treatment for varicose veins. Compression stockings are generally thought to be effective in a range of 20 mmhg to 40mmHg. The Society for Vascular Surgery/American Venous Forum recommends compression therapy of mmhg for patients with symptomatic varicose veins. Compression stockings of 20-30mmHg are available over the counter without a prescription. Greater/long saphenous vein: Superficial vein running the entire length of the leg and is generally 3 mm in its normal state. A typical GSV contains an average of 7 valves throughout its entire length, and it is the most common superficial vein to develop venous reflux. Lesser (small)/short saphenous veins: Superficial vein of the calf and is generally 2.5 mm in its normal state. The small saphenous vein originates at the back of the ankle near the outer malleous bone, and usually runs up the back of the lower leg to the popliteal vein behind the knee. Moderate to severe reflux: In current practice, most vascular laboratories consider the presence of venous flow reversal for greater than 0.5 second with proximal compression, Valsalva maneuver, or distal compression and release to represent pathologic reflux. Perforator veins: These connect superficial veins to deep veins. They contain one-way valves to direct the blood from the superficial system to the deep system and are generally less than 3mm in their normal state. Stab avulsion: This technique is also known as stab/hook phlebectomy. Stab avulsion results in removal of the varicose veins through incisions that are 2-3 mm in length. The veins are hooked with a tiny hook-like instrument and pulled out. The wounds are closed with tapes, not sutures, and the leg is wrapped in elastic compression support. Once healed, the incision sites are almost invisible. Telangiectasia/spider veins: Very small ( 1 mm in diameter) thread veins found commonly just under the surface of the skin, usually not distorting skin or surrounding tissues. Tributary veins: Veins that empty into a larger vein Page 11 of 41

12 Evidence Review Description A variety of treatment modalities are available to treat varicose veins/venous insufficiency, including surgical approaches, thermal ablation, and sclerotherapy. The application of each of these treatment options is influenced by the severity of the symptoms, type of vein, source of venous reflux, and the use of other (prior or concurrent) treatments. Based on the available evidence, clinical input and clinical practice guidelines, the use of endovenous radiofrequency, laser ablation, and microfoam sclerotherapy are considered to improve outcomes when used in the saphenous veins. For treatment of saphenous tributaries at the same time or following treatment of the saphenous vein, stab avulsion, hook phlebectomy, sclerotherapy, or transilluminated powered phlebectomy improve outcomes. Background The venous system of the lower extremities consists of the superficial veins (this includes the greater and lesser saphenous and accessory, or duplicate, veins that travel in parallel with the greater and lesser saphenous veins), the deep system (popliteal and femoral veins), and perforator veins that cross through the fascia and connect the deep and superficial systems. One-way valves are present within all veins to direct the return of blood up the lower limb. Because venous pressure in the deep system is generally greater than that of the superficial system, valve incompetence at any level may lead to backflow (venous reflux) with pooling of blood in superficial veins. Varicose veins with visible varicosities may be the only sign of venous reflux, although itching, heaviness, tension, and pain may also occur. Chronic venous insufficiency secondary to venous reflux can lead to thrombophlebitis, leg ulcerations, and hemorrhage. The CEAP classification considers the clinical, etiologic, anatomic, and pathologic (CEAP) characteristics of venous insufficiency, ranging from class 0 (no visible sign of disease) to class 6 (active ulceration). Treatment of venous reflux/venous insufficiency is aimed at reducing abnormal pressure transmission from the deep to the superficial veins. Conservative medical treatment consists of elevation of the extremities, graded compression, and wound care when indicated. Conventional surgical treatment consists of identifying and correcting the site of reflux by ligation of the incompetent junction followed by stripping of the vein to redirect venous flow through veins with intact valves. While most venous reflux is secondary to incompetent valves at the Page 12 of 41

13 saphenofemoral or saphenopopliteal junctions, reflux may also occur at incompetent valves in the perforator veins or in the deep venous system. The competence of any single valve is not static and may be pressure-dependent. For example, accessory saphenous veins may have independent saphenofemoral or saphenopopliteal junctions that become incompetent when the greater or lesser saphenous veins are eliminated and blood flow is diverted through the accessory veins. Saphenous Veins and Tributaries Saphenous veins include the greater and lesser saphenous and accessory saphenous veins that travel in parallel with the greater or lesser (small) saphenous veins. Tributaries are veins that empty into a larger vein. Treatment of venous reflux typically includes the following: Identification by preoperative Doppler ultrasonography of the valvular incompetence Control of the most proximal point of reflux, traditionally by suture ligation of the incompetent saphenofemoral or saphenopopliteal junction Removal of the superficial vein from circulation, for example by stripping of the greater and/or lesser saphenous veins Removal of varicose tributaries (at the time of the initial treatment or subsequently) by stab avulsion (phlebectomy) or injection sclerotherapy. Minimally invasive alternatives to ligation and stripping have been investigated. These include sclerotherapy, transilluminated-powered phlebotomy, and thermal ablation using cryotherapy, high frequency radiowaves ( khz), or laser energy. Sclerotherapy The objective of sclerotherapy is to destroy the endothelium of the target vessel by injecting an irritant solution (either a detergent, osmotic solution, or chemical irritant), ultimately resulting in the occlusion of the vessel. The success of the treatment depends on accurate injection of the vessel, an adequate injectate volume and concentration of sclerosant, and compression. Historically, larger veins and very tortuous veins were not considered to be good candidates for sclerotherapy due to technical limitations. Technical improvements in sclerotherapy have included the routine use of Duplex ultrasound to target refluxing vessels, luminal compression of the vein with anesthetics, and a foam/sclerosant injectate in place of liquid sclerosant. Foam Page 13 of 41

14 sclerosants are commonly produced by forcibly mixing a gas (eg, air or carbon dioxide) with a liquid sclerosant (eg, polidocanol or sodium tetradecyl sulfate). The foam is produced at the time of treatment. Varithena (previously known as Varisolve, BTG PLC, London) is a proprietary microfoam sclerosant that is dispersed from a canister with a controlled density and more consistent bubble size. Endovenous Mechanochemical Ablation (MCA) Endovenous mechanochemical ablation (MOCA ) utilizes both sclerotherapy and mechanical damage to the lumen. Following ultrasound imaging, a disposable catheter with a motor drive is inserted into the distal end of the target vein and advanced to the saphenofemoral junction. As the catheter is pulled back, a wire rotates at 3500 rpm within the lumen of the vein, abrading the lumen. At the same time, a liquid sclerosant (sodium tetradecyl sulfate) is infused near the rotating wire. It is proposed that mechanical ablation allows for better efficacy of the sclerosant, and results in less pain and risk of nerve injury without need for the tumescent anesthesia used with thermal endovenous ablation techniques (radiofrequency ablation [RFA] and endovenous laser treatment [EVLT]). Thermal Ablation Radiofrequency (RFA) ablation is performed by means of a specially designed catheter inserted through a small incision in the distal medial thigh to within 1 2 cm of the saphenofemoral junction. The catheter is slowly withdrawn, closing the vein. Laser ablation is performed similarly; a laser fiber is introduced into the greater saphenous vein under ultrasound guidance; the laser is activated and slowly removed along the course of the saphenous vein. Cryoablation uses extreme cold to cause injury to the vessel. The objective of endovenous techniques is to cause injury to the vessel, causing retraction and subsequent fibrotic occlusion of the vein. Technical developments since thermal ablation procedures were initially introduced include the use of perivenous tumescent anesthesia, which allows successful treatment of veins larger than 12 mm in diameter and helps to protect adjacent tissue from thermal damage during treatment of the lesser saphenous vein. Page 14 of 41

15 Cyanoacrylate Adhesive for Embolization (CAE) Cyanoacrylate adhesive is a clear, free-flowing liquid that polymerizes in the vessel via an anionic mechanism (ie, polymerizes into a solid material on contact with body fluids or tissue). The adhesive is gradually injected along the length of the vein in conjunction with ultrasound and manual compression. The acute coaptation halts blood flow through the vein until the implanted adhesive becomes fibrotically encapsulated and establishes chronic occlusion of the treated vein. Cyanoacrylate glue has been used as a surgical adhesive and sealant for a variety of indications, including gastrointestinal bleeding, embolization of brain arteriovenous malformations, and to seal surgical incisions or other skin wounds. Transilluminated Powered Phlebectomy (TIPP) Transilluminated powered phlebectomy (TIPP) is an alternative to stab avulsion or hook phlebectomy. This procedure uses 2 instruments: an illuminator which also provides irrigation, and a resector, which has an oscillating tip and can perform suction. Following removal of the saphenous vein, the illuminator is introduced via a small incision in the skin and tumescence solution (anesthetic and epinephrine) is infiltrated along the course of the varicosity. The resector is then inserted under the skin from the opposite direction, and the oscillating tip is placed directly beneath the illuminated veins to fragment and loosen the veins from the supporting tissue. Irrigation from the illuminator is used to clear the vein fragments and blood through aspiration and additional drainage holes. The illuminator and resector tips may then be repositioned, thereby reducing the number of incisions needed when compared with stab avulsion or hook phlebectomy. It has been proposed that TIPP might result in decreased operative time, decreased complications such as bruising, and faster recovery compared to the established procedures. Treatment of Perforator Veins Perforator veins cross through the fascia and connect the deep and superficial venous systems. Incompetent perforating veins were originally addressed with an open surgical procedure, called the Linton procedure, which involved a long medial calf incision to expose all posterior, medial, and paramedial perforators. While this procedure was associated with healing of ulcers, it was largely abandoned due to a high incidence of wound complications. The Linton procedure was subsequently modified by using a series of perpendicular skin flaps instead of a longitudinal skin flap to provide access to incompetent perforator veins in the lower part of the leg. The modified Page 15 of 41

16 Linton procedure may occasionally be used for the closure of incompetent perforator veins that cannot be reached by less invasive procedures. Subfascial endoscopic perforator surgery is a less-invasive surgical procedure for treatment of incompetent perforators and has been reported since the mid-1980s. Guided by Duplex ultrasound scanning, small incisions are made in the skin, and the perforating veins are clipped or divided by endoscopic scissors. The operation can be performed as an outpatient procedure. Endovenous ablation of incompetent perforator veins with sclerotherapy and RFA has also been reported. Other Deep vein valve replacement is being investigated. Outcomes of interest for venous interventions include healing and recurrence, recannulation of the vein, and neovascularization. Recannulation (recanalization) is the restoration of the lumen of a vein after it has been occluded; this occurs more frequently following treatment with endovenous techniques. Neovascularization is the proliferation of new blood vessels in tissue and occurs more frequently following vein stripping. Direct comparisons of durability for endovenous and surgical procedures are complicated by these different mechanisms of recurrence. Relevant safety outcomes include the incidence of paresthesia, thermal skin injury, thrombus formation, thrombophlebitis, wound infection, and transient neurologic effects. Review of Evidence Treatment of Saphenous Reflux Compression Therapy A 2009 Cochrane review on compression for venous leg ulcers included a total of 39 randomized controlled trials (RCTs), with 47 different comparisons. 1 The review was updated in 2012, and included 48 RCTs with 59 different comparisons. 2 Most of the RCTs were small. Objective measures of healing were the time to complete healing, the proportion of ulcers healed within the trial period (typically 12 weeks), the change in ulcer size, and the rate of change in ulcer size. Evidence from 8 trials indicated that venous ulcers healed more rapidly with compression than without. Findings suggested that multicomponent systems (bandages or stockings) were more effective than single-component compression. In addition, multicomponent systems containing an elastic bandage appeared more effective than those composed mainly of inelastic constituents. Although these meta-analyses did not include time to healing, studies included in Page 16 of 41

17 the review reported that the mean time to ulcer healing was approximately 2 months, while the median time to healing in other reports was 3 to 5 months. A Cochrane review on compression stockings for the initial treatment of varicose veins in patients without venous ulceration was published in Included in the review were 7 studies involving 356 participants with varicose veins without healed or active venous ulceration (CEAP [clinical, etiology, anatomy, pathophysiology] classification C2 to C4). Six of the studies compared different types or pressures of stockings. Subjectively, participants symptoms improved, but results were not compared with a control arm. Due primarily to inadequate reporting, the methodologic quality of the included trials was unclear. Meta-analyses were not performed due to inadequate reporting and suspected heterogeneity. The authors concluded that there is insufficient high-quality evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in patients without venous ulceration, or whether any type of stocking is superior to any other type. This Cochrane review was updated in The authors stated: Conclusions from the individual studies regarding the optimum pressure provided by stockings were conflicting, although the results of one study suggested that lower pressured stockings (20 mmhg) may be as effective as higher pressured stockings (30 to 40 mmhg) for relieving symptoms. Conclusions regarding the optimum length of the stockings were inconclusive. No severe or long lasting side effects were noted. The Clinical Practice Guidelines for the Society for Vascular Surgery and the American Venous Forum (Gloviczki, 2011) includes the following recommendations for compression therapy: We suggest compression therapy using moderate pressure (20-30 mm Hg) for patients with symptomatic varicose veins (GRADE 2C) We recommend against compression therapy as the primary treatment of symptomatic varicose veins in patients who are candidates for saphenous vein ablation (GRADE 1B) We recommend compression as the primary therapeutic modality for healing venous ulcers (GRADE 1B). We recommend compression as an adjuvant treatment to superficial vein ablation for the prevention of ulcer recurrence (GRADE 1A). 52 Page 17 of 41

18 Ligation and Stripping Systematic literature reviews published in 2008 indicate a similar healing rate of venous ulcers with superficial vein surgery and conservative compression treatments but a reduction in ulcer recurrence rate with surgery. 4, 5 In general, recurrence rates after ligation and stripping are estimated at around 20%. Jones et al reported on the results of a study that randomized 100 patients with varicose veins to undergo either ligation alone or ligation in conjunction with stripping. 6 At 1 year, reflux was detected in 9% of patients, rising to 26% at 2 years. Rutgers and Kitslaar reported on the results of a trial that randomized 181 limbs to undergo either ligation and stripping or ligation combined with sclerotherapy. 7 At 2 years, Doppler ultrasound demonstrated reflux in approximately 10% of patients after ligation and stripping, increasing to 15% at 3 years. Comparison of Endovenous Ablation and Sclerotherapy with Ligation and Stripping An updated Cochrane review from 2014 compared endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus ligation/stripping for saphenous vein varices. 8 Included in the review were 13 randomized studies with a combined total of 3081 patients. The overall quality of the evidence was moderate. There was no significant difference between sclerotherapy and surgery in the rate of recurrence as rated by clinicians (odds ratio [OR], 1.74; p=0.06) or for symptomatic recurrence (OR=1.28). For endovenous laser ablation (EVLA) versus surgery, there were no significant differences between the treatment groups for clinician noted or symptomatic recurrence, or for recanalization. Neovascularization and technical failure were reduced in the laser group (OR=0.05, p<0.001; and OR=0.29, p<0.001, respectively). For endovenous radiofrequency ablation (RFA) versus surgery, there were no significant differences between the groups in clinician noted recurrence, recanalization, neovascularization, or technical failure. The authors concluded that sclerotherapy, EVLA, and RFA are at least as effective as surgery in the treatment of great saphenous varicose veins. In 2014, Brittenden et al. reported a multicenter randomized trial that compared foam sclerotherapy, EVLA, and surgical treatment in 798 patients. 9 The study was funded by U.K. s Health Technology Assessment Programme of the National Institute for Health Research. Veins greater than 15 mm were excluded from the study. At the 6-week follow-up visit, patients who were assigned to treatment with foam or laser had the option of treatment with foam for any residual varicosities; this was performed in 38% of patients in the foam group and 31% of patients in the EVLA group. Six months after treatment, mean disease-specific quality of life was slightly worse after sclerotherapy than after surgery (p=0.006), and there were more residual varicose veins, although the differences were small. Disease-specific quality of life was similar for Page 18 of 41

19 the laser and surgery groups. The frequency of procedural complications was similar for the foam sclerotherapy (6%) and surgery (7%) groups, but was lower in the laser group (1%). The rate of complications at 6 months (primarily lumpiness and skin staining), was highest for the sclerotherapy group. Endovenous Radiofrequency Ablation (RFA) In 2008, Luebke et al. reported a meta-analysis of 8 studies that included a total of 224 patients who underwent RFA and 204 patients who underwent stripping. 10 There was no significant difference between RFA and surgery in immediate or complete greater saphenous vein occlusion, incomplete greater saphenous vein closure, freedom from reflux, recurrent varicose veins, recanalization, or neovascularization between the 2 treatments. There were significant reductions in tenderness and ecchymosis at 1 week and fewer hematomas at 72 hours, 1 week, and 3 weeks with RFA. Quality-of-life results, including return to normal activity and return to work, favored RFA over surgery. The authors noted that rates of recanalization, retreatment, occlusion, and reflux may alter with longer follow-up and that further RCTs with longer followup are needed. Long-term outcomes of endovenous RFA were reported from the Closure Study Group clinical registry in Thirty-four centers (1,006 patients, 1,222 limbs) participated in the registry, with 12 centers contributing 5-year data (406 limbs). The registry included data on the treatment of 52 lesser saphenous veins and 16 accessory saphenous veins. Follow-up at 1 week showed a 97% anatomic success rate and a decrease in pain in 50% (from 85% to 30%) of patients. An additional 162 failures were identified over the 5 years of follow-up; 129 veins were found to have recanalization, and 33 limbs had reflux in the groin. Logistic regression analysis (risk factors of sex, age, body mass index [BMI]), vein diameter, and catheter pullback speed) showed that BMI was associated with long-term failure. The rate of pull-back speed of the catheter during treatment was associated with failure to occlude or recanalization. Endovenous Laser Ablation (EVLA) The largest trial on EVLA is the 2012 RELACS study, which was a practical design that randomized 400 patients to EVLA performed by a surgeon at 1 site or to ligation and stripping performed by a different surgeon at a second location. 12 At 2-year follow-up, there was no significant difference between the groups for clinically recurrent varicose veins, medical condition on the Homburg Varicose Vein Severity Score, or disease-related quality of life. Page 19 of 41

20 Saphenofemoral reflux was detected by ultrasonography more frequently after endovenous laser treatment (EVLT) (17.8% vs. 1.3%). This study will follow patients for 5 years. Another trial compared EVLA with ligation and stripping in 200 limbs (100 in each group). 13 At 1-year followup, 98% of the limbs were reported to be free of symptoms. At 2-year follow-up, the EVLA group had 2 veins completely reopened and 5 partially reopened, which was significantly greater than in the ligation and stripping group. In the 2013 MAGNA trial, 223 consecutive patients (240 legs) with great saphenous vein reflux were randomized to EVLA, ligation and stripping, or foam sclerotherapy. 14 At 1-year follow-up, the anatomic success rates were similar between EVLA and stripping (88.5% and 88.2%, respectively), which were superior to foam sclerotherapy (72.2%). Ten percent of the stripping group showed neovascularization. Healthrelated quality of life improved in all groups. The CEAP classification improved in all groups with no significant difference between the groups. Transient adverse events were reported in 11 patients after stripping, 7 after EVLA, and 5 after sclerotherapy. At 5-year follow-up, Kaplan- Meier analysis showed obliteration or absence of the great saphenous vein in 85% of patients who underwent conventional surgery and 77% of patients who underwent EVLA (not significantly different). 15 Grade I neovascularization was higher in the conventional surgery group (27% vs 3%, p<0.001), while grade II neovascularization was similar in the 2 groups (17% vs 13%). Literature on isolated treatment of the anterior accessory saphenous vein is limited. In a 2009 study, outcomes from a cohort of 33 patients who underwent EVLA of the anterior accessory saphenous vein were compared with 33 matched controls undergoing EVLA of the greater saphenous vein. 15 In 21 of the patients (64%) in the accessory saphenous vein group, there had been no previous treatment of the greater saphenous vein. At 12-month follow-up, there was no evidence of reflux in these patients, and the treated accessory saphenous vein was not visible with ultrasound. The Aberdeen Varicose Vein Symptom Severity Score had improved in both groups, with no significant difference between the 2 groups. Patient satisfaction scores were also similar. Sclerotherapy In the 2013 MAGNA trial (previously described), 223 consecutive patients (240 legs) with great saphenous vein reflux were randomized to EVLA, ligation and stripping, or physician compounded foam sclerotherapy (1 cc aethoxysclerol 3%: 3 cc air). 14 At 1-year follow-up, the anatomic success rate of foam sclerotherapy (72.2%) was inferior to both EVLA and stripping (88.5% and 88.2%, respectively). Twenty-one patients in the sclerotherapy group had partial occlusion with reflux, though the clinical complaint was completely relieved. At 5-year follow-up, Page 20 of 41

21 obliteration or absence of the greater saphenous vein was observed in only 23% of patients treated with sclerotherapy compared to 85% of patients who underwent conventional surgery and 77% of patients who underwent EVLA. 15 Thirty-two percent of legs treated initially with sclerotherapy required 1 or more reinterventions during follow-up compared with 10% in the conventional surgery and EVLA groups. However, clinically relevant grade II neovascularization was higher in the conventional surgery and EVLA groups (17% and 13%, respectively), compared with the sclerotherapy group (4%). EuroQol-5D scores improved equally in all groups. A 2012 study was a noninferiority trial of foam sclerotherapy versus ligation and stripping in 430 patients. 17 Analysis was per protocol. Forty patients (17%) had repeat sclerotherapy. At 2 years, the probability of clinical recurrence was similar in the 2 groups (11.3% sclerotherapy vs. 9.0% ligation and stripping), although reflux was significantly more frequent in the sclerotherapy group (35% vs. 21%). Thrombophlebitis occurred in 7.4% of patients after sclerotherapy. There were 2 serious adverse events in the sclerotherapy group (deep venous thrombosis and pulmonary emboli) that occurred within 1 week of treatment. In 2013, Varithena microfoam was approved under a new drug application for the treatment of varicose veins. Efficacy data were from 2 randomized, blinded, multicenter studies. 18 One evaluated Varithena at 0.5%, 1.0%, and 2.0% polidocanol and the second evaluated Varithena at 0.5% and 1.0% polidocanol compared with endovenous placebo or a subtherapeutic dose of polidocanol foam. The primary end point was improvement in symptoms at week 8, as measured by the Varicose Vein Symptoms Questionnaire. The improvement in symptoms was greater in the pooled Varithena treatment group (p<0.001) and in each of the individual dose-concentration groups compared with vehicle alone. Secondary and tertiary end points (appearance, duplex ultrasound response, quality of life) were also significantly better for the Varithena groups compared with controls. This second study, called VANISH-2, was published in At the 8-week assessment, there was elimination of reflux and/or occlusion of the previously incompetent vein in 85.6% of the combined 0.5% and 1.0% groups, 59.6% of patients in the 0.125% group, and 1.8% of the placebo group. Analysis of data from both studies showed a dose response from 0.5% to 2.0% for improvement in appearance and from 0.5% to 1.0% for Duplex responders. The 1.0% dose of Varithena was selected for the FDA approval. Safety analysis found deep vein thrombosis detected by ultrasound in 2.8% of Varithena treated patients with 1% of patients having proximal symptomatic thrombi; these were treated with anticoagulants. There was no signal of an increase in neurological adverse events, and there were no adverse cardiac or cardiopulmonary effects following treatment with Varithena injectable foam. Rates of occlusion with Varithena are similar to those reported for EVLA or stripping. A randomized trial comparing EVLA and stripping with this new preparation of foam sclerotherapy is needed to evaluate its comparative effectiveness. Evaluation out to 5 years is continuing. Page 21 of 41

22 Mechanochemical Ablation (MCA) Several prospective series and cohort studies have been reported. One prospective multicenter series evaluated the efficacy of mechanochemical ablation (MCA) of the great saphenous vein in 126 patients in a community setting. 20 Veins were selected that were greater than 4 mm and less than 12 mm in diameter, with an average diameter of 7.3 mm. Closure rates were 100% at 1 week, 98% at 3 months, and 94% at 6 months. The venous clinical severity score decreased from a score of approximately 9 pretreatment to about 3 at 6 months. In 2012, Elias and Raines reported an industry-sponsored safety and efficacy study of MCA with the ClariVein system. 21 Thirty greater saphenous veins in 29 patients were treated with this device. Greater saphenous veins with diameters greater than 12 mm were excluded. At 6-month follow-up, 1 vein had recanalized, for a primary closure rate of 96.7%. No pain during the procedure or adverse events was reported. Another prospective series evaluated MCA of the small saphenous vein in 50 consecutive patients. 22 Only patients with a vein diameter of 2.5 to 11 mm were included. The dose of sclerosant was increased after the first 15 patients. At the 6-week assessment, all treated veins were occluded and at 1-year follow-up, 94% remained occluded. The median visual analog scale score for pain during the procedure was 2 of 10. There were no major complications. Controlled studies with a greater number of subjects and longer follow-up are needed. A 2013 review of MCA notes that a 5-year 840 patient randomized trial comparing ClariVein with RFA began in 2012 in Europe. 23 This trial will provide needed data on the comparative effectiveness of MCA, measured at a longer duration and in a larger population. Early results from this trial (119 patients) indicate that intra-procedural pain is slightly lower with MCA (13.4 mm on a 100-mm scale) compared with RFA (24.4, p=0.001). 24 Cyanoacrylate Adhesion The VenaSeal pivotal study (VeClose) was a multicenter noninferiority trial with 222 patients that compared VenaSeal versus RFA for the treatment of venous reflux. 25, 26 The primary end point, the proportion of patients with complete closure of the target GSV at 3 months measured by ultrasound, was non-inferior to RFA with a 99% closure rate for VenaSeal compared with 96% for RFA. The secondary endpoint of intraoperative pain was similar for the 2 groups (2.2 on a 10-point scale for VenaSeal and 2.4 for RFA, p=0.11). Ecchymosis at day 3 was significantly lower in the cyanoacrylate group; 67.6% of patients treated with cyanoacrylate had no ecchymosis compared with 48.2% of patients following RFA (p<0.01). Scores on the AVVQ and Page 22 of 41

23 Venous Clinical Severity Score improved to a similar extent in the 2 groups. Longer term followup is needed to permit conclusions regarding the durability of this procedure. Twenty-four-month follow-up was reported for 24 of 38 patients enrolled in a study by Almeida et al. 27 Thirty-three month follow-up was reported in 467 veins out of a series of 795 veins (58.7%) treated at 1 institution in Germany. 28 An inflammatory reddening of the skin was observed at approximately 1 week after treatment in 11.7% of cases. No permanent skin responses were observed. Of the 467 veins re-examined, the sealing rate was 97.7%. This series is limited by the high loss to follow-up. Endovenous Cryoablation Klem et al. reported a randomized trial in 2009 that found endovenous cryoablation (n=249) to be inferior to conventional stripping (n=245) for treating patients with symptomatic varicose veins. 29 The percentage of patients with greater saphenous vein remaining was 44% in the endovenous cryoablation group and 15% in the conventional stripping group. The Aberdeen Varicose Vein Questionnaire also showed better results for conventional stripping (score, 11.7) in comparison with cryoablation (score, 8.0). There were no differences between the groups in SF- 36 subscores, and neural damage was the same (12%) in both groups. Disselhoff et al. reported 2 and 5 year outcomes from a randomized trial that compared cryostripping with EVLA. 30, 31 Included were 120 patients with symptomatic uncomplicated varicose veins (CEAP C2) with saphenofemoral incompetence and greater saphenous vein reflux. At 10 days after treatment, EVLA had better results than cryostripping with respect to pain score over the first 10 days (2.9 vs. 4.4), resumption of normal activity (75% vs. 45%) and induration (15% vs. 52%). At 2-year follow-up, freedom from recurrent incompetence was observed in 77% of patients after EVLA and 66% of patients after cryostripping (not significantly different). At 5 years, 36.7% of patients were lost to follow-up; freedom from incompetence and neovascularization was found in 62% of patients treated with EVLA and 51% of patients treated with cryostripping (not significantly different). Neovascularization was more common after cryostripping, but incompetent tributaries were more common after EVLA. There was no significant difference between groups in the Venous Clinical Severity Score or Aberdeen Varicose Vein Severity Score at either 2 or 5 years. Page 23 of 41