Treatment of Superficial Venous Disease Polly Kokinos, MD South - - PDF document

4/4/2019 1

Developments in the Treatment of Superficial Venous Disease

Polly Kokinos, MD South Bay Vascular Center and Vein Institute April 4,2019

Review: Venous Anatomy of the Lower Extremity

1 2

4/4/2019 2

Manifestations and Mechanisms of Venous Insufficiency

Treatment Patterns and Outcomes in Patients with Varicose Veins

 Retrospective review of claims in 2008-2010 of database with 45 million claims  Eligibility: Age over 18, One diagnosis came during time with “varicose veins”(ICD9 454) Had health coverage for at least one year before and two years after the time period above  Eligible to be included in study: 150K claims  Results: 90.8% Female, Mean age 53 years  Treatment used: 100K managed conservatively (70%) 23 K had thermal endovenous treatment 4800 had sclerotherapy 4800 had surgery 11K had multiple modalities  During the 2 year follow-up, 54% of patients treated with interventional treatment had another treatment for varicose veins, however this did not adjust for laterality  (1/3 patients had bilateral disease), or for “staged” treatment of GSV/SSV, varicosities, or perforators. Most of the additional treatments occurred within the first 60 days.

 Am Health Drug Benefits. 2016 Nov; 9(8): 455–465

3 4

4/4/2019 3

Superficial Venous Insufficiency: Treatments

 COMPRESSION THERAPY IS THE CORNERSTONE

OF THERAPY

 High ligation and stripping: rarely done today  Thermal Method: Endovenous ablation using

radiofrequency/laser: FDA approved since 2005

 Non-thermal methods: MOCA( mechanico-chemical

ablation): Clarivein

 Sclerotherapy: Varithena  Glueing of vein: VenaSeal

EVRA Trial: Does treating Superficial Venous Insufficiency help ulcer healing?

 450 patients in the UK  Randomized to early ablation vs. Compression +/- delayed ablation  Outcomes:  time to healing  healing percentage at 24 weeks  recurrence rate 

ulcer-free interval

 QoL Gohel MS, et al, NEJM 2018; 378:2105-2114

5 6

4/4/2019 4

EVRA Trial Results:

 Median time to healing:

56 days vs. 82 days (p=0.001)

 24-week healing

85.6% vs 76.3%

 Ulcer recurrence

11.4% vs 16.5%

 Ulcer-free interval

306 days vs 278 days (p=0.002)

Gohel MS, et al, NEJM 2018; 378:2105-2114

Options for vein treatment 2019

Thermal with tumescent:

 Radiofrequency Ablation( Closure Fast)

 Laser Ablation (EVLT, ELVes, VeinSeal)

Nonthermal Nontumescent:

 Mechanical Occlusion chemically assisted ablation

(Clarivein)  Cyanoacrylate Closure (Venaseal)  Polidocanol endovenous microfoam (Varithena)

Nonthermal Tumescent:

 Inversion Stripping with Tumescence 7 8

4/4/2019 5

Considerations in the treatment of superficial venous insufficiency and varicose veins

 Vein diameter  Vein length (especially for recurrent reflux

• r accessory veins)

 Tortuosity  Vein location (suprafascial vs intrafascial)  Vein location (above vs below the knee)  Concerns regarding neighboring structures

(ie. nerves)

 Presence of perforators  Disease state (ulcers, lipodermatosclerosis, swelling)

9 10

4/4/2019 6

Problems with RF/Laser:

 Intra-operative discomfort of patient  Length of procedure  Thermal injury to surrounding structures ,

especially below the knee

 Need for tumescent  Problems if vein too superficial or tortuous  Development of reflux in accessory branches  Need for compression postop

Long term durability of treatment

 Hamman, et al: Meta-analysis of 3 RCT and follow-up

studies of 10 RCTs:

 >5 yr follow-up on treatment of GSVs  Surgery vs EVLA vs USG-guided sclerotherapy  5 year occlusion rates with laser or RF both about

96.5%

11 12

4/4/2019 7

Clarivein( Merrit Medical)

 Mechanicochemical ablation (MOCA)-mechanical agitation of the vessel endothelia by rotating catheter tip combined with injection of a liquid sclerosant  FDA approved in 2014  Medicare reimbursement in

2017 (codes 36473/4)

Clarivein

Advantages:

 No tumescent  Single entry site  Minimal intraop pain  No bruising  No nerve injury

 Disadvantages:

 Need for compression  Difficult if tortuous vein  Insurance coverage

issues

 Recannalization  Throw away a whole

power motor unit each time

13 14

4/4/2019 8

Clarivein results

 Phlebology. 2017 Dec;32(10):649-657.  Mechanochemical endovenous ablation of saphenous

veins using the ClariVein: A systematic review

 Review of 10 unique cohorts including 1521 veins  Pooled short-term (6 months) success 92%  Mid-term success: 2 years: 91% 3 years 87%  Major complication rate 0.2% (DVT, nerve injury)

Venaseal (Medtronic)

Website describes as “The only non-thermal, Non-tumescent, non-sclerosant Procedure” to close the vein Uses cyanoacrylate “superglue” type of adhesive to seal the vein FDA approval: 2015 Medicare coverage: codes 36482 and 36483 in 2018

15 16

4/4/2019 9

Venaseal (Cyanoacrylate) VeClose Study 2017

 242 patients with symptomatic

GSV reflux

 At 3 years 92% had complete

closure of GSV vs 92% with Closure Fast (no difference)

 Statistical improvement in QOL

and VSS scores seen in both groups

17 18

4/4/2019 10

Venaseal

Advantages:

 No tumescent  Single needlestick  No need for compression hose post-op  No nerve injury  Excellent long term closure rate

Disadvantages:

 Phlebitis rate up to 16%  Equally painful to RF during procedure  Difficult to advance the stiff Venaseal catheter in tortuous veins, postthrombotic veins  Can feel glue if GSV is superficial (permanent)  Allergic reactions rare but require surgical excision of glue

Varithena (BTG)

Polidocanol injectable foam FDA approved: 2013 Medicare approval 2018: CPT codes 36465/6 19 20

4/4/2019 11

• Oxygen:CO2 ratio of 65:35 with low (<0.8%)

nitrogen content

• Polidocanol liquid to gas ratio of approximately 1:7

by volume

• Median bubble diameter of 100 µm and no

bubbles greater than 500 µm

21

Varithena Foam Composition

• VARITHENA was evaluated in two randomized,

blinded, multicenter clinical trials designed to assess the efficacy and safety of VARITHENA compared with placebo in the treatment of GSV or major accessory vein reflux disease.

• VANISH-1 and VANISH-2 Studies showed

statistically significant improvement in symptoms and appearance of varicose vein disease

• Downplay duplex “responders” as 1 year results

showed 73% success.

22

Varithena Clinical Trials

21 22

4/4/2019 12

Santangelo, KT. Treating C6 Venous Disease Requires Tandem Effort. evtoday.com January 2017.

Varithena

 Advantages:

 Can treat tortuous GSV and varicosities  No tumescent  Fast procedure  Comparable in net cost to RF  Little to no intraop/postop pain

 Disadvantages:

 Multiple needle sticks  Canister needs to be used

• ver a short time to treat

multiple patients  Need to wear compression for 2 weeks  Outcomes >1 year unclear  Medicare will only reimburse for GSV not SSV

23 24

4/4/2019 13

Theraclion’s Echopulse

 HIFU (High-Intensity Focused Ultrasound) technology focuses high- energy ultrasound to deliver a large amount of acoustic energy to a targeted area, quickly heating localised areas of tissue.  The energy of the ultrasound is concentrated in a small area. The energy released quickly raises the temperature in this area (to 80-95°C). This produces therapeutic effects through coagulation and then necrosis of the tissue in the targeted area  This has been used to treat thyroid nodules and breast fibroadenomas and is now in clinical trials to treat varicose veins.  May be most helpful in treating recurrences, tortuous veins, “stumps”

Superficial Venous Treatments

 All quite safe , outpatient procedures with good short-

term outcomes

 All improve symptomatology of heaviness, aching,

swelling, itching

 Only thermal methods have long-term follow-up and

success rates at 15 years of up to 88% by duplex

• ultrasound. There was no clinical recurrence in the
• riginally treated veins, however “de novo” reflux was

found in 51.6% of patients in veins that were originally competent.

 Eur J Vasc Endovasc Surg. 2017 Sep;54(3):357-362

25 26

4/4/2019 14

Pharmacotherapy for Chronic Venous insufficiency

 MPFF: Micronized Purified Flavonoid Fraction  Diosmin + Hesperidin  Most investigated venoactive medication: Daflon 500  NOT APPROVED IN THE US  Mechanism: inhibits noradrenaline degradation,

leukocyte adhesion and activiation, TNF, VEGF

 Side effects: N/V in up to 7%  Cost: $15-30/month

MPFF

 RELIEF trial: European trial with >5000 pts in 23

countries: Significant improvement in leg aching, heaviness, edema, and QoL

 A meta-analysis of 5 prospective, randomized trials in

723 patients demonstrated a 32% improvement in venous ulcer HEALING with its use (p=0.03)

Coleridge-Smith. Eur J Vasc Endovasc Surg. 2005;30:198-208

27 28

4/4/2019 15

Diosmiplex (Vasculera)

 Only MPPF that is FDA approved for use in USA  Classified as a “Medical Food”  Addresses the Biochemical Pathway to Avoid The

Progression to Chronic Venous Disease (CVD)

 Take once a day  Side Effects: Mild, GI upset, Headache  Must get through special pharmacy-- $50/month

Society Recommendations

29 30

4/4/2019 16

Non Venoactive Medications

 Pentoxifylline  ASA  Danazol  Stanozolol

Pentoxifylline

 Methyl-xanthine derivative  Dose 400-800 mg BID  Mechanism of action: 

Reduces platelet aggregation



Inhibits WBC activation and adhesion



Inhibits TNF-alpha and leukotrienes



Improves RBC deformability



Reduces viscosity

 Side effects: GI (dyspepsia/nausea/vomiting)

31 32

4/4/2019 17

Pentoxifylline for treating Venous Leg Ulcers: Cochrane Library Review 2012

 12 trials (864 patients); 11 placebo controlled  Pentoxifylline is more effective than placebo for

complete ulcer healing and improvement

 Pentoxifylline +compression is more effective than

placebo+compression

 Pentoxifylline without compression is more effective

than placebo

 Conclusions: Pentoxifylline is an effective adjunct to

compression for treating leg ulcers and may be effective in the absence of compression

33 34

4/4/2019 18

Conclusions

 Multiple options exist to treat reflux in the GSV/SSV/other axial veins  These methods are all minimally invasive, effective, with low

complication rates

 Endovenous thermal treatments remain excellent procedures with well studied and very high long term success rates  Chemical adhesive technologies have high success rates but variable rates of phlebitis/allergic type reactions that can require secondary procedures  Microfoam technologies are fast and safe but have limited durability  MOCA has excellent short term closure results and clinical improvement but significant deterioration in results after two years.

Thank You!

35 36

4/4/2019 19

• None of the 1333 patients in the VARITHENA trials

experienced clinically important neurological or visual adverse events suggestive of cerebral gas embolism.

37

Varithena Foam – Neuro Complications

Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation for the treatment of superficial venous insufficiency

 Objective  This study measured patient outcomes among symptomatic patients with superficial chronic venous insufficiency who were treated with retrograde ultrasound-guided polidocanol microfoam 1% in a community setting.  Methods  Between March 2015 and June 2017, 250 symptomatic patients with C2-C6 chronic venous insufficiency received polidocanol microfoam 1% and were followed for 16 ± 7 months. Sixteen of the 250 patients (6.4%) had skin ulcers, and 56 (22.4%) were treated previously with thermal or surgical interventions. All patients underwent a duplex ultrasound venous incompetence study to map perforators and veins to be treated. Incompetent veins were accessed with a micropuncture needle distal to the midthigh perforator, approximately 10 cm above the knee fold. The leg was then elevated 45°. Under ultrasound guidance, the incompetent

greater saphenous vein was closed with polidocanol microfoam1%. A second injection was administered through the same catheter directing the microfoamto flow in a retrograde fashion through the incompetent venous valves to the ankle.

JVS-VL: July 2018Volume 6, Issue 4, Pages 477–484 Steven T. Deak, MD, PhD, FACS

37 38

4/4/2019 20

Retrograde administration of ultrasound-guided endovenous microfoam chemical ablation for the treatment of superficial venous insufficiency  Results  All patients completed the initial treatment; 55 (22.0%) required planned secondary treatment during the follow-up period for residual venous reflux in the below-knee greater saphenous vein. Complete elimination of venous valvular reflux and symptom improvement was documented in 236 patients (94.4%). Minor adverse events included asymptomatic deep vein thrombi (n = 2), common femoral vein thrombus extension (n = 1), and superficial venous thrombi (n = 4). Of the 16 patients with skin ulcers, 10 were C6 patients and 80% experienced wound closure within 4 weeks of treatment.  Conclusions  Retrograde administration of polidocanol microfoam 1% is a safe and effective treatment with important clinical benefit for superficial venous insufficiency in community practice.

39