Disclosure Mark Meissner, M.D.

I have no financial relationship(s) to disclose.

Mark H. Meissner, MD Professor of Surgery

University of Washington School of Medicine

Seattle, WA

Outcomes of Venous Interventions in C5-6 Disease

Chronic Venous Insufficiency

5% prevalence (US) of CEAP class 4 - 6

6 - 7 million people with skin changes

400,000 - 500,000 people with ulcers

90% require medical treatment

Direct medical costs of $600 - $2000

> $10,000 if not healed within 12 weeks

Treatment options Medical

Compression

Pharmacologic adjuncts

Wound care adjuncts

Surgical Superficial venous surgery

Perforator interruption

Valvular reconstruction

Iliac stenting

C5

C6

Compression for Ulceration (C6) Cullum et al; Cochrane Reviews 2001

Compression

(# healed)

No Compression

(# healed)

Relative Risk

(95% CI)

Charles 19/27 6/23 2.70 (1.30 - 5.60)

Eriksson 9/17 7/17 1.29 (0.62 - 2.65)

Kitka 21/30 15/39 1.82 (1.15 - 2.89)

Rubin 18/19 7/17 2.30 (1.29 - 4.10)

Sikes 17/21 15/21 1.13 (0.81 - 1.59)

Taylor 12/18 4/18 3.00 (1.19 - 7.56)

0.1 0.2 0.5 1 2 5 10

Observational study of 119 patients

34% bed rest followed by ECS

66% ambulatory treatment with ECS

Complete Healing

Compliant 97%

Noncompliant 55%

Recurrence (5 yr life table)

Compliant - 29%

Noncompliant - 100%

Compression for Venous Leg Ulcers Mayberry, Surgery 1991

Pentoxifylline: A Meta-Analysis Jull et al, Lancet 2002

Author Trental

n/N

Control

n/N Relative Risk RR

Barbarino 4 / 6 1 / 6 4.00

Colgan 23 / 38 12 / 42 2.12

Dale 65 / 101 52 / 99 1.23

Falanga 61 / 86 28 / 45 1.14

Schurmann 2 / 12 3 / 12 0.67

Total 155 / 243 96 / 204 1.30 Favors

Control

Favors

Trental 1.0

Surgery for C5-6 Disease The ESCHAR Trial - Barwell JR, Lancet 2004

Prospective randomized trial

High ligation, stripping, phlebectomy

Multilayer compression bandaging

500 patients with CEAP 5 and 6 disease

Endpoints

24 week ulcer healing (NS)

Compression - 65%

Surgery + Compression - 65%

12 month ulcer recurrence (p < .0001)

Compression - 28%

Surgery + Compression - 12%

Ulcer healing

Freedom from recurrence

IPV Interruption & Ulcer Recurrence O’Donnell TO, J Vasc Surg 2008

Systematic review of RCTs for venous ulceration (C6)

Compression vs perforator surgery (2 trials)

Compression vs superficial surgery (2 trials)

Author N Trial

Intervention

Zamboni 47 Superficial

Surgery

ESCHAR 428 Superficial

Surgery

Van Gent 196 Perforator

Surgery

Stacey 41 Perforator

Surgery

Risk Ratio (95% CI)

0.5 0.2 0.1 0.05 0.02 1 2 5 10 20 50

Favors Surgery Favors Compression

The Problem of Perforator “Incompetence”

Perforator reflux often resolves with correction of superficial reflux

Perforator incompetence unlikely to be the primary cause of recurrent / residual varicosities

Perforator interruption does not reduce recurrent ulceration

Current studies have often taken non-specific approach

Ability to distinguish important perforators is limited

Unknown role for identification and interruption of critical perforators in future

Available Evidence Suggests…

But…

Defining Important Perforators Gloviczki et al, J Vasc Surg 2011

> 3.5 mm diameter

Outward flow > 0.5 sec

Localized in the area of a healed or

active ulcer

Think “Pathologic”

NOT

“Incompetent”

Perforators

Deep Venous Valvular Reconstruction

Populations not strictly comparable

Iliac Stenting for C5-6 Disease Raju s, J Vasc Surg 2002

304 limbs with iliac obstruction

Etiology

Primary (nonthrombotic) – 142 (47%)

Postthrombotic – 162 (53%)

Outcome Pre-Stent Post-Stent

Class 5 & 6 Active Ulcer - 49

Healed Ulcer - 13

68% Healing

Recurrence - 2 (3%)

Swelling

(Grade 1 - 3) 2 (0 - 3) 1 (0 - 3)

Pain

(VAS, 0 - 10) 4 (0 - 9) 0 (0 - 9)

GRADE Recommendations Guyatt et al, Chest 2006

GRADE Benefit vs

Risk Methodology Implication

1A Clear High quality Strong recommendation; Precise estimate of

effect unlikely to change; Generalizeable

1B Clear Moderate Strong recommendation; May change with

further research; Applies to most patients

1C Clear Low Strong recommendation; Likely to change

change with better evidence

2A Balanced High quality Weak recommendation, Action differs with

patient/societal values

2B Balanced Moderate Weak recommendation, Action differs with

patient/societal values

2C Uncertain Low Very weak recommendation, Alternatives

equally reasonable

Interventions For C5-6 Disease

Treatment Outcome Methodology Grade

Compression Ulcer healing RCT 1B

Debridement Accelerated healing Observational 1C

Pentoxyfylline Ulcer healing RCT 2B

Wound care adjuncts Ulcer healing RTC 2A/B/C

Superficial surgery Ulcer healing RTC 1A Against

Systemic antibiotics Ulcer healing RTC 1B Against

Compression Ulcer recurrence Observational 1A

Superficial surgery Ulcer recurrence RTC 1A

Venous ablation Ulcer recurrence Indirect 1B

Deep reconstruction Ulcer recurrence Case series 2C

Perforator interruption Ulcer recurrence RTC 2C

Treatment Outcome Methodology Grade

Compression Ulcer healing RCT 1B

Debridement Accelerated healing Observational 1C

Pentoxyfylline Ulcer healing RCT 2B

Wound care adjuncts Ulcer healing RTC 2A/B/C

Superficial surgery Ulcer healing RTC 1A Against

Systemic antibiotics Ulcer healing RTC 1B Against