Venous Disease and Treatment Options for your Patients

1. Venous Disease and Treatment Options for your Patients VIVEK AGRAWAL, MD MAKSYM DYMEK, MD FREDDY KATAI, MD Chicago vascular and interventional clinic

2. In the U.S., approximately 25 Million people suffer from venous reflux disease, the underlying cause for most varicose veins1 Photos courtesy of Rajabrata Sarkar, MD, PhD.

3. Prevalence and Etiology of Venous Insufficiency • Venous reflux disease is 2x more prevalent than coronary heart disease (CHD) and 5x more prevalent than peripheral arterial disease (PAD)1

4. Prevalence and Etiology of Venous Insufficiency • Of the estimated 25 million people with symptomatic superficial venous reflux1 : • Only 1.7 million seek treatment annually2 • Over 23 million go untreated Prevalence by Age and Gender3

5. Possible Risk Factors4,5,6,7 and Symptoms of Venous Insufficiency

6. Venous System • Venous blood flows from the capillaries to the heart • Flow occurs against gravity • Muscular compression of the veins • Negative intrathoracic pressure • Calf muscle pump • Low flow, low pressure system

7. Pathophysiology of Venous Insufficiency

8. Manifestations of Venous Insufficiency Superficial venous reflux is progressive and if left untreated, may worsen over time. Below are manifestations of the disease.8 Varicose Veins Swollen Legs Skin Changes Skin Ulcers 20+ million 2 to 6 million 500,000 U.S. Prevalence Photos courtesy of Rajabrata Sarkar, MD, PhD.

9. Treatment Options Conservative Therapies: • Exercise • Leg elevation • Compression Stockings • Unna Boot These therapies treat the symptoms, not the underlying cause… Surgical Treatments: • Vein Stripping & Ligation

10. Treatment Options (cont’d) Non-Surgical Treatments: • Endovenous ablation Ultrasound Diagnostic Study • Required in order to determine the source of reflux • Evaluate for venous occlusion or thrombus • Map the course of the incompetent superficial veins

11. The VNUS ClosureTM Procedure • The VNUS Closure procedure is a minimally invasive treatment alternative for patients with symptomatic superficial venous reflux and varicose veins • Using a catheter-based approach, the VNUS RFG Plus™ generator delivers radiofrequency (RF) energy to the ClosureFAST™ catheter • The catheter heats the vein wall and contracts the vein wall collagen, thereby occluding the vein

12. VNUS ClosureTM Procedure Animation

13. Efficacy of the ClosureFAST™ Catheter The ClosureFAST™ catheter ablates the vein in 7cm segments with 20-second treatment cycles, resulting in vein shrinkage and occlusion. A multicenter prospective study has shown 93% occlusion at 3 years post-treatment.9 Visual Results The VNUS Closure TM procedure is covered by most insurance for patients diagnosed with venous reflux. Post-treatment* Pre-treatment *Individual results may vary

14. VNUS ClosureTM ProcedureSafety Summary INDICATIONS: The VNUS Closure™ procedures treat leg veins in the superficial and perforating systems that have venous reflux, the underlying cause of varicose veins and venous ulcers. Individual results may vary based on each patient’s condition. CONTRAINDICATIONS: Patients with thrombus in the vein segment to be treated.  Caution: No data exists regarding the use of this catheter in patients with documented peripheral arterial disease. The same care should be taken in the treatment of patients with significant peripheral arterial disease as would be taken with a traditional vein ligation and stripping procedure. POTENTIAL COMPLICATIONS: Potential complications include, but are not limited to, the following: vessel perforation, thrombosis, pulmonary embolism, phlebitis, infection, adjacent nerve injury, arteriovenous fistula, skin burn, hematoma or discoloration.   

15. Comparison of Endovenous Techniques: the RECOVERY Study Perforator Veins and Wound Care

16. Comparison of Endovenous Techniques

17. RECOVERY Trial10Radiofrequency Endovenous ClosureFAST™ versus 980nm Laser Ablation for the Treatment of Great Saphenous Reflux • A comparison of the patient experience between those treated with the ClosureFAST™ Catheter vs. 980nm Endovenous Laser • Six center, single-blinded randomized trial • 69 patients; 87 limbs treated (46 CLF; 41 EVL) • Patient follow up at 2, 7, 14, and 30 days after treatment

18. RECOVERY Trial10: Pain Score at Follow Up Visits Scale: 0 none to 10 max p < 0.0001 p < 0.0001 NS p < 0.0001

19. RECOVERY Trial10: Tenderness Score at Follow Up Visits Scale: 0 none to 10 max p = 0.0048 p = 0.0036 p = 0.0005 NS

20. RECOVERY Trial10: Ecchymosis % of Patients Suffering from Moderate to Severe Ecchymosis* (Bruising) After Treatment *defined as bruising over greater than 25% of the treated surface area p < 0.0001 ClosureFAST™ Laser

21. RECOVERY Trial10: Venous Clinical Severity Score (VCSS) NS p = 0.0009 p = 0.0002 p = 0.0035 NS

22. RECOVERY Trial10: Quality of Life Score: Global Note: Lower score reflects better QOL NS p = 0.03 p < 0.001 NS p = 0.003

23. RECOVERY Trial10: Conclusion Compared to 980 nm laser ablation, at 14 days, treatment with ClosureFAST™ produced significantly: - Less pain p < 0.0001 - Less bruising p < 0.0001 - Less tenderness p = 0.005 - Greater improvement in VCSS scores p = 0.0035 - Better quality of life p = 0.045

24. Ablation Comparison(simulation in beef liver)

26. Perforator Veins & Wound Care

27. Systemic Reflux in Venous Ulceration Incompetent perforators found in 63% of venous ulcer patients11 Photo courtesy of David MacMillian MD

28. Perforating Veins and Reflux • Perforator valves maintain one-way flow from superficial to deep veins • Perforator valve failure causes: • Higher venous pressure and GSV/branch dilation • Increasing pressure results in GSV valve failure • Additional vein branches become varicose • Further GSV incompetence and dilation

29. VNUS ClosureRFS™ • Ultrasound exam to diagnose vein reflux • Outpatient or hospital procedure • Local or general anesthetic • Quick return to normal activities – often within one day12 Click graphic to play video

30. Venous Ulcer Patient Outcomes • Treating both superficial and perforator vein insufficiency results in • Faster ulcer heal time • Lower ulcer recurrence than compression therapy alone12,13,14,15,16 Pre-treatment 8 weeks post-treatment Photos courtesy of David MacMillian, MD

31. VNUS ClosureRFS™Safety Summary INDICATIONS: The VNUS ClosureRFSstylet is intended for use in vessel and tissue coagulation including treatment of incompetent (i.e., refluxing) perforator and tributary veins. CONTRAINDICATIONS: Patients with thrombus in the vessel segment to be treated. Precaution: For patients with a pacemaker, internal defibrillator or other active implanted device, consult the cardiologist and the manufacturer of the active implanted device. Continuous patient monitoring during the procedure is recommended. Evaluate the patient and the implanted active device post-procedure. Keep all power cords and the instrument cable away from the location of the pacemaker or leads, defibrillator or the implanted active device. Caution: No data exists regarding the use of this device in patients with documented peripheral arterial disease. Care should be taken in using this device for occlusive venous surgery in patients with significant peripheral arterial disease. POTENTIAL COMPLICATIONS: The potential complications include, but are not limited to, the following: arteriovenous fistula, thrombosis, pulmonary embolism, phlebitis, hematoma, infection, nerve damage, skin burns.

32. References • Brand FN, Dannenberg AL, Abbott RD, Kannel WB. The epidemiology of varicose veins: the Framingham Study. Am J Prev Med 1988; 4(2):96-101 • US Markets for Varicose Vein Treatment Devices 2006, Millennium Research Group 2005. • Coon WW, Willis PW, Keller JB. Venous thromboembolism and other venous disease in the Tecumseh Community Health Study Circulation 1973; 48:839-846 • Maurins U, Hoffmann BH, Lösch C, Jöckel KH, Rabe E, Pannier F. Distribution and prevalence of reflux in the superficial and deep venous system—results from the Bonn vein study, Germany. J Vasc Surg 2008;48:680-87 • Criqui MH et al. Epidemiology of chronic peripheral venous disease; JJ Bergan Editor, The Vein Book, Elsevier Academic Press (2007): 30 • Chiesa R, Marone EM, Limoni C, Volonte M, Schaefer E, Petrini O. Chronic venous insufficiency in Italy: the 24-cities cohort study. Eur J Vasc Endovasc Surg. 2005;30:422-429 • Rabe E, Pannier F. Epidemiology of chronic venous disorders; P. Glovicki, Editor, Handbook of venous disorders (3rd edition), Hodder Arnold (2009); 109 • White JV, Ryjewski C: Chronic venous insufficiency. Perspect Vasc Surg Endovasc Ther 2005;17:319-27 • Dietzek A, Current Data on Radiofrequency Ablation With The ClosureFAST Catheter, 37th Annual Veith Symposium,  November 17th, 2010 New York • Almeida JI, Kaufman J, Goeckeritz O, et al. Radiofrequency Endovenous ClosureFAST versus Laser Ablation for the Treatment of Great Saphenous Reflux: A Multicenter, Single-Blinded, Randomized Study (Recovery Study).JVIR; June 2009

33. References (cont’d) • Hanrahn L. et al. Distribution of valvular incompetence in patients with venous stasis ulceration. JVS 13,6, 805-812 June 1991 • Roth S, Endovenous radiofrequency ablation of superficial and perforator veins, Surg Clin N Am 87:1267-1284(2007) • Gohel M, Barwell R, et al. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomized controlled trial. BMJ;335;83(2007) • Nelzen O. Fransson I. True long-term healing and recurrence of venous leg ulcers following SEPS combined with superficial venous surgery: a prospective study. Eur J Vasc Endovasc Surg 34, 605-612(2007) • Zamboni P. et al. Minimally invasive surgical management of primary venous ulcers vs. compression treatment: a randomized clinical trial. Eur J Vasc Endovasc Surg 25,313- 318(2003) • Marsh P, Price BA, Holdstock JM, Whiteley MS, One-year outcomes of radiofrequency ablation of incompetent perforator veins using the radiofrequency stylet device, Phlebology;25:79-84(2010)