Best strategy to improve patients quality of life dr. Patrianef, SpB(K)BV PIT VII IDI Kota Bogor, 1-2 November 2014

1. Best Strategy to Improve Patient’s Quality of Life
PATRIANEF
Vascular and Endovascular Division
Department of Surgery –FMUI –Ciptomangunkusumo Hospital
September 6nd 2014

4. Chronic Venous Disease (CVD)- Definition
“Chronic Venous Disease (CVD) is defined as an abnormally functioning venous system due to venous valvularincompetence with or without associated venous outflow obstruction, which may affect the superficial venous system, the deep venous system, or both.”

5. Each situationEach diseasehas different perspectives

6. Evaluation of:
Symptoms
◦Consumptionofanalgesic–Pain
◦Visualscale–Pain
◦Numericscale–Pain,Legheaviness,Cramps,Swelling,Heatsensation
◦Reductioninthenumberofpatientspresentingaspecificsymptom
Signs
◦Edema–Perimeter(Leg-o-meter);Volume(Waterdisplacement)
◦LegUlcer–Size+TimetoHealingPhysicians’ Perspective

7. 1 -EklofB et al. J VascSurg2009;49:498-501; 2 -EklofB. et al. J VascSurg2004;40:1248-1252.
Signs 1,2
Symptoms 1
•C0: No visible signs
•C1: Telangiectasia, reticular veins
•C2: Varicose veins
•C3: Edema
•C4: Skin changes
C4a:pigmentation, eczema,
C4b: lipodermatosclerosis, atrophie blanche.
•C5: Healed Venous ulcer
•C6: Active Venous ulcer
•Tingling
•Aching, Burning
•Pain
•Muscle cramps, Swelling
•Throbbing
•Heaviness
•Itching skin
•Restless legs
•Leg-tiredness
•Fatigue
Chronic venous disease-related symptomsand signs are clearly described(from consensus documents)
Conclusion Clinical aspects

8. ◦Quantitativemeasurementtools
Pain assessment tool
Remarks
Analgesic consumption
Only practitioner-reported data are reliable
10-cm visual analogue scale (VAS)
Good reproducibility
Numerical scale (usually from 0 to 5)
Good reproducibility
Others:
McGill Pain Questionnaire
Brief Pain Inventory
Multidimensional Pain Inventory
Impractical in routine
Close to a quality-of-life scale
Skewed towards back pain
Adapted from AllaertFA.Medicographia2006;28:137-140SymptomsPhysicians’ Perspective

9. ◦Assessingtreatmenteffectonsigns:
Whichendpoints?
End point
Need for a consensus about
Edema
How great a decrease in leg volume constitutes a clinical improvement?
Varicose veins
Cosmetic satisfaction of patients? Absence of pain?
Absence of reflux? No recurrence? Quality of life?
Cost effectiveness?
Venous ulcer
Complete re-epithelizationof the wound? Time to healing? Ability to walk without reopening of the wound? Frequency of dressing change? Frequency of admission to hospital? SignsPhysicians’ Perspective

10. Instrument
Purpose
Remarks
CEAP classification,
the AVF Ad-hoc Committee, 1995, 2004
For patient’sdescriptiononly
Not for scoring(not sensitive to changes)
•Venous Clinical Severity Score (VCSS)
•Venous Disability Score (VDS)
•Venous Segmental Disease Score(VSDS) Rutherford, 2000
•To assesschanges over timeor in response to therapy f
•To assess theability to workan 8-hour day with or without a “support device”
•To generate agrade based on reflux or obstruction
•Imperfect tool forevaluation of the earlystages
•Daily activities not taken into consideration f
•Arbitrary and difficult to grade
Adapted from Vasquez MA. In press
◦FromtheCEAPtoitsadjunctsSignsPhysicians’ Perspective

11. Patient’s Perspective Type of instruments:
Preference about care received
Health behaviours
Subjective symptoms
Patient satisfaction
Health related quality of life
PRO–Instruments that measures perceived health outcomes or endpoints assessed by patients reports (questionnaires)

12. Quality of Life (QoL) WHO definition
Multidimensional concept, including:
Physical
Psychological
Social
Patient perception about disease (subjective state of health)
Information –burden illness
“The product of the interplay between social, health, economic and environmental conditions which affect human and social development”
Alliot-Launois, 2003; Pitsch, 2008;Kahn, 2008; Vasquez , 2008

13. Quality of Life (QoL)
Pitsch, 2008; Vasquez , 2008;Alliot-Launois, 2003
Generic instruments:
Nottingham Health Profile (NHP)
Short Form 36 Health Survey (SF-36)
Disease-specific instruments
Charing Cross Venous Ulceration Questionnaire (CXVUQ)
Aberdeen Varicose Vein Questionnaire (AVVQ)
Venous Insufficiency Epidemiological and Economic Study (VEINES)
Chronic Venous Insufficiency Questionnaire (CIVIQ)
Evaluation:

14. Symptomsand qualityof life
•The % of symptomaticpatients increases with increasing CEAP class.1- 3
•There is a significant association between increasing CEAP class and reduced quality of life (QOL),4 even after adjustment for confounding variables.5
•The QOL impairment associated with CVD is equal to the QOL impairment associated with other chronic and severe diseases (C3=cancer and diabetes6;C5-C6= heart failure7).
1. Rabe E. Int Angiol. 2012;31:105-15. -2. Chiesa R.J Vasc Surg. 2007; 46:322-330.
3. Carpentier P. J Vasc Surg. 2003; 37:827-833. -4. Franks PJ. Qual Life Res. 2001;10:693-700.
5. Kahn Sr. J Vasc Surg. 2004;39:823-828. -6. Andreozzi GM et al. Int Angiol. 2005;24:272-277.
7. Ware JE. 1994. NewEngland Medical Center.

15. Burdenof ChronicVenousDisease•CVD(C1 to C6) affects75 % of adults in the USA1 and around 64% worldwide.2•CVI (C3 to C6) affects 16% of adults in the USA1and24% worldwide.2•Venous ulcers (C6) affect 2.5 million patients/year in the USA.3
•70%of venous ulcers recurwithin 5 years of healing.4
1-Passman MA.J Vasc Surg2011;54:2S-9S 2-Rabe E. Int Angiol 2012;31:105-115.
3-Eklof B.J Vasc Surg2004;40:1248-1252. 4-Callam MJ. BMJ.1987;294:1389-1391.

16. Epidemiologyof chronicvenousdisease
CEAP clinicalclass (% individuals)
USA1
Germany2
Worldwide3
C0
26
10
36
C1
33
59
22
C2
24
14
18
C3
9
13
15
C4
7
3
7
C5
0.5
0.6
1.4
C6
0.2
0.1
0.6
1-McLafferty RB et al. J Vasc Surg. 2008;48:394-399.
2-Rabe E et al. Phlebologie. 2003;32:1-14.
3-Rabe E et al. Int Angiol. 2012;31:105-115.
In the USA, more than 50% of adults present with telangiectases or varices
(not adjusted for age, gender, or BMI)

17. Epidemiologyof chronicvenousdisease
CEAP clinicalclass (% individuals)
USA1
Germany2
Worldwide3
C0
26
10
36
C1
33
59
22
C2
24
14
18
C3
9
13
15
C4
7
3
7
C5
0.5
0.6
1.4
C6
0.2
0.1
0.6
In the USA, more than 50% of adults present with telangiectases or varices
(not adjusted for age, gender, or BMI)
1-McLafferty RB et al. J Vasc Surg. 2008;48:394-399.
2-Rabe E et al. Phlebologie. 2003;32:1-14.
3-Rabe E et al. Int Angiol. 2012;31:105-115.

18. The frequencyof varicoseveinsincreaseswitholderage
1-Abramson JH et al. J Epidemiol Community Health. 1981; 35: 213-217.
2-Coon WW et al. Circulation1973 ; 48:839-846.

19. The prevalenceof venousulceralsoincreaseswithage
CornwallJV et al. Br J Surg. 1986;73:693-696.

20. Socioeconomicaspects of chronicvenousdisease
•Overall annual costs:
–900 million €in Western Europe (2% of health care budget)1
–Equivalent to 2.5 billion €in the USA
–Greaterthan the amount spent for treatment of arterial disease
•Annual loss of work days:
–2 million work days lost due to venous ulcers in the USA2
–4 million work days lost due chronic venous disease (C1-C6) in France
–Ranked 14thfor work absenteeismin Brazil
–Cost for loss of work days varies between 270 million €(Germany), 320 million €(France), and 3 billion USD per year in the USA2
•CVD is progressive, increases with age, and has a propensity to recur. This further increases costs.
1-Ruckley CV. Angiology.1997;48:67-9. 2-McGuckin M. Am J Surg. 2002;183:132-137.

21. Etiology
•Reflux 80%
•Venous obstruction 18-28%
–Resultant edema and skin changes = Postthrombotic syndrome
•Muscle Pump Dysfunction

22. Risk factors
•Age: Aging causes wear and tear. Eventually, that wear causes the valves to malfunction.
•Sex: Women > Men. Hormonal changes during pregnancy or menopause. Progesterone relaxes venous walls. HRT / OCP may increase the risk of varicose veins.
•Genetics
•Obesity: Increases venous HTN.
•Standing for long periods of time.Prolonged immobile standing impairs venous return. Fowkes, FG, Lee, AJ, Evans, CJ, et al. Lifestyle risk factors for lower limb venous reflux in the general population: Edinburgh Vein Study. Int J Epidemiol 2001; 30:846.
Sadick, NS. Predisposing factors of varicose and telangiectatic leg veins. J Dermatol Surg Oncol 1992; 18:883. Iannuzzi, A, Panico, S, Ciardullo, AV, et al. Varicose veins of the lower limbs and venous capacitance in postmenopausal women: relationship with obesity. J Vasc Surg 2002; 36:965.
Evans, CJ, Fowkes, FG, Hajivassiliou, CA, et al. Epidemiology of varicose veins. A review. Int Angiol 1994; 13:263.

23. Incidence
25-50% of adult women
15-30% of adult men
1-2% with Active or Healed Ulceration
Patrick H. Carpentier, Hildegard R. Maricq, Christine Biro, Claire O. Poncot-Makinen, Alain Franco, Prevalence, risk factors, and clinical patterns of chronic venous disorders of lower limbs: A population-based study in France, Journal of Vascular Surgery, Volume 40, Issue 4, October 2004, Pages 650-659, ISSN 0741-5214, DOI: 10.1016/j.jvs.2004.07.025.
Coon WW, Willis PW III, Keller JB. Venous thromboembolism and other venous disease in the Tecumseh community health study. Circulation 1973; 48: 839–846.
Franks PJ, Wright DD, Moffatt CJ, Stirling J, Fletcher AE, Bulpitt CJ et al. Prevalence of venous disease: a community study in west London. Eur J Surg 1992; 158: 143–147.
Bradbury A, Evans C, Allan P, Lee A, Ruckley CV, Fowkes FG. What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey. BMJ 1999; 318: 353–356

24. Chronic venous disease
•Most common vascular disorder
•3 Billion US dollars spent a year for treatment
•3 % of the total Heath care Budget
•2 million USA work days lost per year

25. Class C0s: Symptoms without visible or palpable signs of venous disease
Class C1a,s: Telangiectasiasor reticular veins
a = asymptomatic
s = symptomatic Class C2a,s: Varicose veins Class C3a,s: Edema Class C4a,s: Skin changes ascribed to venous disease, eg, pigmentation, venous eczema, lipodermatosclerosis Class C5a,s: Skin changes with healed ulceration Class C6a,s: Skin changes with active ulcerationTheCEAP*classification–IdentificationofCVDpatientprofiles8
8. Allegra C, Antignani PL, Bergan J, Carpentier P, et al. J Vasc Surg. 2003;37:129-313.
* CEAP: Clinical, Etiological, Anatomical, Pathophysiological.

26. C1
C4
C2
C3
C6
C5

27. MACRO circulationMICRO circulationProgression of chronicvenousdisease: venoushypertension iskey
Adapted from Bergan JJ et al. N Engl J Med. 2006;355:488-498, and from Eberhardt RT et al. Circulation. 2005; 111:2398-2409SymptomsSymptomsC0sSymptomsSymptomsVaricose Veins (C2)
RefluxEdema (C3) Skin Changes (C4)
Vein wall
remodeling
Valve
damage
Capillary
leakage
Capillary
damageVenous Ulcer (C5,6)

28. Altered patterns of blood flow,
Change in shear stress
Genetic predisposition,
obesity, pregnancy, ..
Environmental factors
repeated over time
Chronic inflammation in vein wall and valve
Remodeling in venous wall and valves
Valve failure, reflux
Chronic hypertension
Adapted from JJ Bergan et al. N Engl J Med 2006 355:488-498
Shear stress dependent leukocyte-endothelial interaction
Activation
of
C nociceptors
Pain
Venous hypertension is linked to
venous inflammation

29. “ Treatment to inhibit inflammation may offer the greatest opportunity to prevent disease-related complications.
Drugs can attenuate various elements of the inflammatory cascade, particularly the leukocyte–endothelium interactions that are important in many aspects of the disease»

30. Am J Pathol. 1983; 113:341-358.

31. Leukocytes and changes in venous valves
Courtesy Schmid Schönbein G
flow direction

32. Increased Capillary PermeabilityAdapted from Schmid-Schönbein G N. The Vein Book 2007 Academic Press
Hypertension is transmitted to capillaries
EDEMA
SKIN
CHANGES

33. Lymphatic overloadAdapted from Perrin M, Ramelet AA.Eur J Vasc Endovasc Surg. 2011; 41:117-125.
Lymphatic drainage is disturbed Pitting edema(Lymphedema)

34. Examination
1. Valsavatest and The Trendelenburgtest
Used to assess the competence of SFJ
2. Tourniquet test
Similar as trendelenburgtest, uses a tourniquet
Assess perforator vein
3. PerthesTest
Indicated deep venous incompetence.
This is a painful and rarely used test.
All of these examination are rarely used, only when duplex scanning or dopplerare not available
J Vasc Surg 2011;53:2s-48s

35. Non invasive measurement
Ultrasound
1980, gold standard method instead of phlebography
1990, color dopplerimproved the reliability
Diagnostic and interventional guided treatment
Photophletysmography
Ambulatory venous pressure measurement
Van der Bremmer et al. Ann Vasc Surg 2010; 24: 426-432
J Vasc Surg 2011;53:2s-48s

36. Therapy
•Education
•Compression
•Drugs
•Physioterapy

37. TREATMENT
•Limit the disease progression
•Lifestyle changes
•Compression stocking is the basic and the most used ( Grade I A,B & Grade 2 C)
•Exercise
Conservative
Leopardi et al. Systematic Review of Treatments for Varicose Veins. Ann Vasc Surg 2009

38. Medicine
•Venoactivedrugs ( Grade 2 B)
–Pentoxiphylline
–Saponins
–Flavonoids:
•rutoside, •diosmin, •hesperidin, •MPFF
–Synthetic
•Calcium dobesilate, naftazone, benzarone
•Reduce edema and restless leg syndrome, improve healing of venous ulcer
J Vasc Surg 2011;53:2s-48sThe most effective venoactivedrugs according to Cohranereview

39. Quality-of-life improvement parallelssymptom improvementParameterN=3995Change in symptomsPatients with symptom improvement, N (%) Increase in CIVIQ score between Day 0 and Day 180
Sensation of swelling
Improved*
2134 (69)
21.1 +16.8
Heaviness
Improved*
2778 (74)
20.1 +16.2
Cramps
Improved*
2189 (79)
21.1 +16.4
Pain
Improved§
1560 (80)
23.8 +16.2
Very much improved**
442 (23)
29.2 +16.9
* Improved: decrease of one class on 5-point scale. §Improved pain: decrease of 2.5 to 5 cm on VAS.
** Very much impoved pain: decrease of ≥5 cm on VAS.
Launois R, Mansilha A et al. Eur J Vasc Endovasc Surg. 2010;40:783-789.
In C0s to C4s patients

40. ReferenceRegimen(nb of enrolled patients) Changes inPainFunctional discomfortSensationof swellingLeg heaviness
Chassignolleet al. 1
Daflon 500 mg (18) vs placebo (18)
Notassessed

Notassessed

Gillyet al. 2
Daflon 500 mg (76) vs placebo (74)




Cospiteet al. 3
Daflon 500 mg (43) vs single diosmin (45)

Notassessed
NS

NS, not significant; + P<.05; ++ P<.01; +++ P<.001 Daflon 500 mg vs comparator
1. Chassignolle J-F et al. JInt Med1987;99 (Suppl.):32-7. -2.Gilly R et al. Phlebology1994;9 (2): 67-70.3. Cospite M et al. Int Angiol1989; 8 (4 suppl): 61-65. Significant improvement ofvenous symptoms in well-designed trials

41. Significant reduction of leg painassociated with venous ulcer
% Patients without pain
N=459 * P =.0023 **P <.001
*
**
**
23
28
37
Lok C. Abstract presented at the 7th meeting of the EVF, London, UK, 29thJune-1stJuly, 2006

42. Significant reduction of leg edema which is often associated with venous pain
Population size
N=463
N=165
N=90
N=45
N=497
Allaert FA. Int Angiol2012;31:310-5.

43. Venous pain is a nociceptiveresponse to venous inflammation and therefore difficult to express
•Heaviness
•Pain, aching
•Sensation of swelling
•Burning
•Night cramps
•Tingling
•Itching
•Restless legs
•Leg tiredness, fatigue
1. Eklof B et al. J Vasc Surg. 2009;49:498-501. -2. Strigo IA et al. Pain. 2002;97:235-246.
3. Vital A et al. Angiology. 2010;19:73-77. Nociceptive responsevia C-fibers 3
Probably expressthe same symptom 1
=
Diffuse pain 2

44. Vein-specific anti-inflammatory action
Adapted from Shoab SS et al. Eur J Vasc Endovasc Surg .1999;17:313-318.
Leukocyte
ICAM-1
Daflon500 mg
Daflon 500 mg
CD11b/CD18
VLA-4
VCAM-1

45. Adapted from Coleridge Smith P. In Ruckley, Fowkes, Bradbury, eds. London, UK: Springer- Verlag; 1999:51-70. Damage induced by leukocyte migration at the levelof the venous valves is present at the onset of the diseaseTheleukocyte–AcentralroleinthepathogenesisofCVD

46. VenoactiveDrugs: Action
Macrocirculation: Increase venous tone, attenuate leucocyte-endothelial interaction
Microcirculation: Increase capillary resistance and reduce capillary filtration, increase lymphatic drainage, reduce inflammation, decrease blood viscosity.

47. Document developed under the auspices of:
•The European Venous Forum
•The International Union of Angiology
•The Cardiovascular Disease Educational and Research Trust, UK
•L’Union Internationale de Phlébologie
On the initiative of the European Venous ForumInternational Guidelines for management of CVD (2013)

48. Updated recommendations for
VADs according to the GRADE system
Indication Venoactive drug Recommen
dation
Quality of
evidence
Code
Relief of symptoms in C0s to
C4s patients, when no other
anatomical lesions and/or
pathophysiological anomalies
are present
• MPFF (Daflon 500)
• Non micronized diosmins
• Rutins (Venoruton)
• Calcium dob. (Doxium)
• Horse chestnut
• Ruscus extracts
• Strong
• Weak
•Weak
•Weak
•Weak
• Weak
•Moderate
•Poor
•Moderate
•Moderate
• Low
• Low
1B
2C
2B
2B
2B
2B
Healing of primary ulcer, as
an adjunct to local therapy and
compressive or/and operative
treatment
(Coleridge Smith, 2009)
• MPFF (Daflon 500) • Strong •Moderate 1B
To be published by end 2013.

49. Treatment Sclerotherapy(Grade1 B)
Small non-saphenousvaricose veins (less than 5 mm),
Perforator veins
Residual or recurrent varicosities following surgery
Telangiectasia
Reticular veins
To initiate
Inflammation,
Occlusion and
Scarring
US guided
Foam sclerotherapy( Grade 1 B )
Catheter directed
Complication: blistering and ulceration 7.1%, phlebitis 15.4%, staining 7.7%
Leopardi et al. Systematic Review of Treatments for Varicose Veins. Ann Vasc Surg 2009

50. Surface /skin laser therapy•Telangiectasias, reticular veins, small varicose veins <5mm

53. Treatment•Ambulatoryphlebectomy( Grade 1 B)
•For larger veins
•Below SFJ and SPJ
•Not including the GSV or SSV
•Without reflux
•Complication: blistering 31%, phlebitis 12%, hematoma•Junction ligation with or without vein stripping
•When GSV and SSV have reflux
•Ligation alone  high recurrence
•Ligation and stripping treatment of choice ( Grade 2 B)
Leopardi et al. Systematic Review of Treatments for Varicose Veins. Ann Vasc Surg 2009

54. TIPP-Transilluminated powered phlebectomy ( Grade 2 C)
“LIPOSUCTION OF VEIN”
Safe and effective for vein excision
Complication: cellulitis 2.2%; abscess 0.4%; hematoma 3.4%; residual varicose 1.1%; cutaneous nerve damage 2.2%, seroma 2.9%
The Vein Book 2007
Kiw JW, Surgery Today 2013;43:62-66

55. Subfascial endoscopic perforator vein ligation (SEPS) ( grade 2 C)
•Refractory symptoms, ulceration, recurrent ulceration.
•Perforators divided electrocautery, harmonic scalpel or clipped.
•1140 limbs overall ulcer healing in 88% Kalra, M, Gloviczki, P. Surgical treatment of venous ulcers: role of subfascial endoscopic perforator vein ligation. Surg Clin North Am 2003; 83:671.

56. Treatment
•RFA and EVLT ( Grade 1 B)
•Heat-generating laser fiber via catheter
•Heat source: Laser or radiofrequency
•Endothelial and vessel wall damage
J Vasc Surg 2011;53:2s-48s

60. Mechanicochemicalendovenousablation
•A new alternative treatment
•Endovenous mechanical and chemical sclerotherapy
•Technical success rate: initial 100%; after 1 year 94%
•No major complication
ESVS 2012.jejvs.2012.12.004
Van Eekeren et al. J Endovasc Ther 2011;18:328-334

61. TakeHome Messages
•The mechanisms resulting in venous pain involve:
–The presence of nerve structures (C-fibers) in the vein wall and perivenous space close to the capillaries
–Local inflammation mediated by activated leukocytes
•MPFF inhibits:
–Leukocyteactivation
–Subsequent venous inflammation
May provide an explanation for MPFF’s benefits on venous pain and quality of life

62. Practical use
•Treatment of symptoms and edemalikely to be ofvenous origin.1
•May be combined with sclerotherapy,endovenous treatment or opensurgery for the treatment of varicose veins.2-4
•Adjunctive treatment in venous leg ulcer (VLU) healing and for relief of VLU-associated symptoms.5
1. Lyseng-Williamson K et al. Drugs.2003;63:71-100 -2. Veverkova L et al. Phlebolymphology. 2006; 13:195-201 -3. Pokrovsky AV et al. Angiol Sosus Khir. 2007; 3:47-55-4. Cazaubon M et al. Angiologie. 2011;15: 554-560 -5. Coleridge-Smith P et al. Eur J Vasc Endovasc Surg. 2005;30:198-208.

63. Suggestion•Varicose: –phlebectomy–GSV varicesnot related to reflux sclerotherapy–GSV plus reflux surgery or foam sclerotherapy•Ligation without stripping is more effective than phlebectomyalone. •EVLT and RFA are better than surgery in regard to QOL, return to work etc•EVLT and RFA are considered as an effective alternative to surgery, as safe as surgery with long- term safety supported by case evidence.

64. Healthy leg is our aim
•Varicose is not just a cosmetic problem, but ….
•Varicose is a disease entity which can reduce the QOL

65. Thank You