Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medical management of lower extremity chronic venous disease

Patrick C Alguire, MD, FACP
Barbara M Mathes, MD, FACP, FAAD
Section Editors
John F Eidt, MD
Joseph L Mills, Sr, MD
Deputy Editor
Kathryn A Collins, MD, PhD, FACS


Venous hypertension is associated with histologic and ultrastructural changes in the capillary and lymphatic microcirculation that produce important physiologic changes, which include capillary leak, fibrin deposition, erythrocyte and leukocyte sequestration, thrombocytosis, and inflammation. These processes impair oxygenation of the skin and subcutaneous tissues. The clinical manifestations of severe venous hypertension and tissue hypoxia are edema, hyperpigmentation, subcutaneous fibrosis, and ulcer formation.

The medical management of chronic venous disease with and without ulceration is discussed here. The etiology, presentation, and pathophysiology of chronic venous disorders are discussed elsewhere:

(See "Classification of lower extremity chronic venous disorders".)

(See "Clinical manifestations of lower extremity chronic venous disease".)

(See "Pathophysiology of chronic venous disease".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 07, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Herschthal J, Kirsner RS. Current management of venous ulcers: an evidence-based review. Surg Technol Int 2008; 17:77.
  2. Douglas WS, Simpson NB. Guidelines for the management of chronic venous leg ulceration. Report of a multidisciplinary workshop. British Association of Dermatologists and the Research Unit of the Royal College of Physicians. Br J Dermatol 1995; 132:446.
  3. Howard DP, Howard A, Kothari A, et al. The role of superficial venous surgery in the management of venous ulcers: a systematic review. Eur J Vasc Endovasc Surg 2008; 36:458.
  4. Myers MB, Cherry G, Heimburger S, et al. The effect of edema and external pressure on wound healing. Arch Surg 1967; 94:218.
  5. Abu-Own A, Scurr JH, Coleridge Smith PD. Effect of leg elevation on the skin microcirculation in chronic venous insufficiency. J Vasc Surg 1994; 20:705.
  6. Burnand KG, O'Donnell TF Jr, Thomas ML, Browse NL. The relative importance of incompetent communicating veins in the production of varicose veins and venous ulcers. Surgery 1977; 82:9.
  7. Padberg FT Jr, Johnston MV, Sisto SA. Structured exercise improves calf muscle pump function in chronic venous insufficiency: a randomized trial. J Vasc Surg 2004; 39:79.
  8. Yang D, Vandongen YK, Stacey MC. Changes in calf muscle function in chronic venous disease. Cardiovasc Surg 1999; 7:451.
  9. Kan YM, Delis KT. Hemodynamic effects of supervised calf muscle exercise in patients with venous leg ulceration: a prospective controlled study. Arch Surg 2001; 136:1364.
  10. Milic DJ, Zivic SS, Bogdanovic DC, et al. Risk factors related to the failure of venous leg ulcers to heal with compression treatment. J Vasc Surg 2009; 49:1242.
  11. Simka M. Calf muscle pump impairment and delayed healing of venous leg ulcers: air plethysmographic findings. J Dermatol 2007; 34:537.
  12. Araki CT, Back TL, Padberg FT, et al. The significance of calf muscle pump function in venous ulceration. J Vasc Surg 1994; 20:872.
  13. Heinen MM, van der Vleuten C, de Rooij MJ, et al. Physical activity and adherence to compression therapy in patients with venous leg ulcers. Arch Dermatol 2007; 143:1283.
  14. de Araujo T, Valencia I, Federman DG, Kirsner RS. Managing the patient with venous ulcers. Ann Intern Med 2003; 138:326.
  15. Norgren L. Elastic compression stockings--an evaluation with foot volumetry, strain-gauge plethysmography and photoplethysmography. Acta Chir Scand 1988; 154:505.
  16. Norris CS, Turley G, Barnes RW. Noninvasive quantification of ambulatory venous hemodynamics during elastic compressive therapy. Angiology 1984; 35:560.
  17. Labropoulos N, Leon M, Volteas N, Nicolaides AN. Acute and long-term effect of elastic stockings in patients with varicose veins. Int Angiol 1994; 13:119.
  18. Shingler S, Robertson L, Boghossian S, Stewart M. Compression stockings for the initial treatment of varicose veins in patients without venous ulceration. Cochrane Database Syst Rev 2013; :CD008819.
  19. Lawrence PF, Chandra A, Wu M, et al. Classification of proximal endovenous closure levels and treatment algorithm. J Vasc Surg 2010; 52:388.
  20. Wu B, Lu J, Yang M, Xu T. Sulodexide for treating venous leg ulcers. Cochrane Database Syst Rev 2016; :CD010694.
  21. Martinez-Zapata MJ, Vernooij RW, Uriona Tuma SM, et al. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev 2016; 4:CD003229.
  22. Martinez MJ, Bonfill X, Moreno RM, et al. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev 2005; :CD003229.
  23. Perrin M, Ramelet AA. Pharmacological treatment of primary chronic venous disease: rationale, results and unanswered questions. Eur J Vasc Endovasc Surg 2011; 41:117.
  24. Nicolaides AN, Allegra C, Bergan J, et al. Management of chronic venous disorders of the lower limbs: guidelines according to scientific evidence. Int Angiol 2008; 27:1.
  25. Belczak SQ, Sincos IR, Campos W, et al. Veno-active drugs for chronic venous disease: A randomized, double-blind, placebo-controlled parallel-design trial. Phlebology 2014; 29:454.
  26. Bush R, Comerota A, Meissner M, et al. Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF). Phlebology 2017; 32:3.
  27. Allaert FA. Meta-analysis of the impact of the principal venoactive drugs agents on malleolar venous edema. Int Angiol 2012; 31:310.
  28. Lacroix I, Beau AB, Hurault-Delarue C, et al. First epidemiological data for venotonics in pregnancy from the EFEMERIS database. Phlebology 2016; 31:344.
  29. MacLennan WJ, Wilson J, Rattenhuber V, et al. Hydroxyethylrutosides in elderly patients with chronic venous insufficiency: its efficacy and tolerability. Gerontology 1994; 40:45.
  30. Wadworth AN, Faulds D. Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Drugs 1992; 44:1013.
  31. Poynard T, Valterio C. Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. Vasa 1994; 23:244.
  32. Rehn D, Unkauf M, Klein P, et al. Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Arzneimittelforschung 1996; 46:483.
  33. Unkauf M, Rehn D, Klinger J, et al. Investigation of the efficacy of oxerutins compared to placebo in patients with chronic venous insufficiency treated with compression stockings. Arzneimittelforschung 1996; 46:478.
  34. Scallon C, Bell-Syer SE, Aziz Z. Flavonoids for treating venous leg ulcers. Cochrane Database Syst Rev 2013; :CD006477.
  35. Diehm C, Trampisch HJ, Lange S, Schmidt C. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet 1996; 347:292.
  36. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2012/06/WC500129249.pdf (Accessed on May 12, 2014).
  37. Longiave D, Omini C, Nicosia S, Berti F. The mode of action of aescin on isolated veins: relationship with PGF2 alpha. Pharmacol Res Commun 1978; 10:145.
  38. Pittler MH, Ernst E. Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. Arch Dermatol 1998; 134:1356.
  39. Siebert U, Brach M, Sroczynski G, Berla K. Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies. Int Angiol 2002; 21:305.
  40. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev 2012; 11:CD003230.
  41. Smith PC. Daflon 500 mg and venous leg ulcer: new results from a meta-analysis. Angiology 2005; 56 Suppl 1:S33.
  42. Guilhou JJ, Dereure O, Marzin L, et al. Efficacy of Daflon 500 mg in venous leg ulcer healing: a double-blind, randomized, controlled versus placebo trial in 107 patients. Angiology 1997; 48:77.
  43. Gliñski W, Chodynicka B, Roszkiewicz J, et al.. The beneficial augmentative effect of micronised purified flavonoid fraction (MPFF) on the healing of leg ulcers: An open, multicentre, controlled, randomised study. Phlebology 1999; 14:151.
  44. Roztocil K, Stvrtinová V, Strejcek J. Efficacy of a 6-month treatment with Daflon 500 mg in patients with venous leg ulcers associated with chronic venous insufficiency. Int Angiol 2003; 22:24.
  45. Pósfai E, Bánhidy F, Czeizel AE. Teratogenic effect of hydroxyethylrutoside, a flavonoid derivate drug--a population-based case-control study. J Matern Fetal Neonatal Med 2014; 27:1093.
  46. Lyseng-Williamson KA, Perry CM. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs 2003; 63:71.
  47. Summary of product characteristics Dafllon500 mg http://www.servier.com/sites/default/files/spc_daflon500_0.pdf.
  48. Layton AM, Ibbotson SH, Davies JA, Goodfield MJ. Randomised trial of oral aspirin for chronic venous leg ulcers. Lancet 1994; 344:164.
  49. Goodfield MJ. A relative thrombocytosis and elevated mean platelet volume are features of gravitational disease. Br J Dermatol 1986; 115:521.
  50. del Río Solá ML, Antonio J, Fajardo G, Vaquero Puerta C. Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency. Ann Vasc Surg 2012; 26:620.
  51. Burnand K, Clemenson G, Morland M, et al. Venous lipodermatosclerosis: treatment by fibrinolytic enhancement and elastic compression. Br Med J 1980; 280:7.
  52. McMullin GM, Watkin GT, Coleridge Smith PD, Scurr JH. Efficacy of fibrinolytic enhancement with stanozolol in the treatment of venous insufficiency. Aust N Z J Surg 1991; 61:306.
  53. Jull AB, Arroll B, Parag V, Waters J. Pentoxifylline for treating venous leg ulcers. Cochrane Database Syst Rev 2012; 12:CD001733.
  54. Varatharajan L, Thapar A, Lane T, et al. Pharmacological adjuncts for chronic venous ulcer healing: a systematic review. Phlebology 2016; 31:356.
  55. Falanga V, Fujitani RM, Diaz C, et al. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial. Wound Repair Regen 1999; 7:208.
  56. Lindemann S, Gierer C, Darius H. Prostacyclin inhibits adhesion of polymorphonuclear leukocytes to human vascular endothelial cells due to adhesion molecule independent regulatory mechanisms. Basic Res Cardiol 2003; 98:8.
  57. Ferrara F, Meli F, Raimondi F, et al. The treatment of venous leg ulcers: a new therapeutic use of iloprost. Ann Surg 2007; 246:860.
  58. Andreozzi GM. Editorial: sulodexide, an old drug with recent renewed interest. Curr Vasc Pharmacol 2013; 11:352.
  59. Coccheri S, Scondotto G, Agnelli G, et al. Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers. Thromb Haemost 2002; 87:947.
  60. Pescador R, Capuzzi L, Mantovani M, et al. Defibrotide: properties and clinical use of an old/new drug. Vascul Pharmacol 2013; 59:1.
  61. Palmer KJ, Goa KL. Defibrotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in vascular disorders. Drugs 1993; 45:259.
  62. Shai A, Halevy S. Direct triggers for ulceration in patients with venous insufficiency. Int J Dermatol 2005; 44:1006.
  63. Huovinen S, Kotilainen P, Järvinen H, et al. Comparison of ciprofloxacin or trimethoprim therapy for venous leg ulcers: results of a pilot study. J Am Acad Dermatol 1994; 31:279.
  64. Lineaweaver W, Howard R, Soucy D, et al. Topical antimicrobial toxicity. Arch Surg 1985; 120:267.
  65. Alinovi A, Bassissi P, Pini M. Systemic administration of antibiotics in the management of venous ulcers. A randomized clinical trial. J Am Acad Dermatol 1986; 15:186.
  66. Briggs M, Nelson EA, Martyn-St James M. Topical agents or dressings for pain in venous leg ulcers. Cochrane Database Syst Rev 2012; 11:CD001177.
  67. O'Meara S, Al-Kurdi D, Ologun Y, et al. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev 2014; :CD003557.
  68. Zenilman J, Valle MF, Malas MB, et al.. Chronic Venous Ulcers: A Comparative Effectiveness Review of Treatment Modalities. Agency for Healthcare Research and Quality; Rockville, MD 2013.
  69. Jull AB, Walker N, Deshpande S. Honey as a topical treatment for wounds. Cochrane Database Syst Rev 2013; :CD005083.
  70. Michanek A, Hansson C, Berg G, Månesköld-Claes A. [Iodine-induced hyperthyroidism after cadexomer iodine treatment of leg ulcers]. Lakartidningen 1998; 95:5755.
  71. Lansdown AB, Williams A, Chandler S, Benfield S. Silver absorption and antibacterial efficacy of silver dressings. J Wound Care 2005; 14:155.
  72. Miller AC, Rashid RM, Falzon L, et al. Silver sulfadiazine for the treatment of partial-thickness burns and venous stasis ulcers. J Am Acad Dermatol 2012; 66:e159.
  73. Geronemus RG, Mertz PM, Eaglstein WH. Wound healing. The effects of topical antimicrobial agents. Arch Dermatol 1979; 115:1311.
  74. Kjolseth D, Frank JM, Barker JH, et al. Comparison of the effects of commonly used wound agents on epithelialization and neovascularization. J Am Coll Surg 1994; 179:305.
  75. Foresman PA, Payne DS, Becker D, et al. A relative toxicity index for wound cleansers. Wounds 1993; 5:226.
  76. Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group. J Vasc Surg 1995; 21:71.
  77. Robson MC, Phillips LG, Thomason A, et al. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet 1992; 339:23.
  78. Mustoe TA, Cutler NR, Allman RM, et al. A phase II study to evaluate recombinant platelet-derived growth factor-BB in the treatment of stage 3 and 4 pressure ulcers. Arch Surg 1994; 129:213.
  79. Richard JL, Parer-Richard C, Daures JP, et al. Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot, randomized, double-blind, placebo-controlled study. Diabetes Care 1995; 18:64.
  80. Falanga V, Eaglstein WH, Bucalo B, et al. Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. J Dermatol Surg Oncol 1992; 18:604.
  81. Marques da Costa R, Jesus FM, Aniceto C, Mendes M. Double-blind randomized placebo-controlled trial of the use of granulocyte-macrophage colony-stimulating factor in chronic leg ulcers. Am J Surg 1997; 173:165.
  82. Da Costa RM, Ribeiro Jesus FM, Aniceto C, Mendes M. Randomized, double-blind, placebo-controlled, dose- ranging study of granulocyte-macrophage colony stimulating factor in patients with chronic venous leg ulcers. Wound Repair Regen 1999; 7:17.
  83. Kirsner RS, Marston WA, Snyder RJ, et al. Spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2012; 380:977.
  84. Goedkoop R, Juliet R, You PH, et al. Wound stimulation by growth-arrested human keratinocytes and fibroblasts: HP802-247, a new-generation allogeneic tissue engineering product. Dermatology 2010; 220:114.
  85. Kircik LH, Dickerson JE Jr, Kitten C, et al. Allogeneic growth arrested keratinocytes and fibroblasts delivered in a fibrin spray accelerate healing in Mohs micrographic surgery wounds. J Drugs Dermatol 2013; 12:558.
  86. Kirsner RS, Marston WA, Snyder RJ, et al. Durability of healing from spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: a 6-month follow-up. Wound Repair Regen 2013; 21:682.
  87. Lantis JC 2nd, Marston WA, Farber A, et al. The influence of patient and wound variables on healing of venous leg ulcers in a randomized controlled trial of growth-arrested allogeneic keratinocytes and fibroblasts. J Vasc Surg 2013; 58:433.
  88. WINTER GD. Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young domestic pig. Nature 1962; 193:293.
  89. Ryan TJ. Wound dressing. Dermatol Clin 1993; 11:207.
  90. Sibbald RG, Contreras-Ruiz J, Coutts P, et al. Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Adv Skin Wound Care 2007; 20:549.
  91. Moore RA, Liedl DA, Jenkins S, Andrews KL. Using a silver-coated polymeric substrate for the management of chronic ulcerations: the initial Mayo Clinic experience. Adv Skin Wound Care 2008; 21:517.
  92. Local applications to wounds--II. Dressings for wounds and ulcers. Drug Ther Bull 1991; 29:97.
  93. O'Donnell TF Jr, Lau J. A systematic review of randomized controlled trials of wound dressings for chronic venous ulcer. J Vasc Surg 2006; 44:1118.
  94. O'Meara S, Martyn-St James M, Adderley UJ. Alginate dressings for venous leg ulcers. Cochrane Database Syst Rev 2015; :CD010182.
  95. Palfreyman SJ, Nelson EA, Lochiel R, Michaels JA. Dressings for healing venous leg ulcers. Cochrane Database Syst Rev 2006; :CD001103.
  96. O'Meara S, Martyn-St James M. Alginate dressings for venous leg ulcers. Cochrane Database Syst Rev 2013; :CD010182.
  97. O'Meara S, Martyn-St James M. Foam dressings for venous leg ulcers. Cochrane Database Syst Rev 2013; :CD009907.
  98. Carter MJ, Tingley-Kelley K, Warriner RA 3rd. Silver treatments and silver-impregnated dressings for the healing of leg wounds and ulcers: a systematic review and meta-analysis. J Am Acad Dermatol 2010; 63:668.
  99. Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev 2007; :CD005486.
  100. Nelson EA, Bell-Syer SE. Compression for preventing recurrence of venous ulcers. Cochrane Database Syst Rev 2012; :CD002303.
  101. Falanga V, Sabolinski M. A bilayered living skin construct (APLIGRAF) accelerates complete closure of hard-to-heal venous ulcers. Wound Repair Regen 1999; 7:201.
  102. Marston WA. Dermagraft, a bioengineered human dermal equivalent for the treatment of chronic nonhealing diabetic foot ulcer. Expert Rev Med Devices 2004; 1:21.
  103. Park CA, Defranzo AJ, Marks MW, Molnar JA. Outpatient reconstruction using integra* and subatmospheric pressure. Ann Plast Surg 2009; 62:164.
  104. Falanga V, Margolis D, Alvarez O, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol 1998; 134:293.
  105. Kranke P, Bennett MH, Martyn-St James M, et al. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev 2012; :CD004123.
  106. Aziz Z, Cullum N. Electromagnetic therapy for treating venous leg ulcers. Cochrane Database Syst Rev 2015; :CD002933.
  107. Aziz Z, Cullum N, Flemming K. Electromagnetic therapy for treating venous leg ulcers. Cochrane Database Syst Rev 2013; :CD002933.
  108. Flemming K, Cullum N. Therapeutic ultrasound for venous leg ulcers. Cochrane Database Syst Rev 2000; :CD001180.
  109. Weingarten MS. State-of-the-art treatment of chronic venous disease. Clin Infect Dis 2001; 32:949.
  110. Nelson EA, Mani R, Thomas K, Vowden K. Intermittent pneumatic compression for treating venous leg ulcers. Cochrane Database Syst Rev 2011; :CD001899.
  111. Mayberry JC, Moneta GL, Taylor LM Jr, Porter JM. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery 1991; 109:575.
  112. O'Donnell TF Jr. The present status of surgery of the superficial venous system in the management of venous ulcer and the evidence for the role of perforator interruption. J Vasc Surg 2008; 48:1044.
  113. Harding KG. Leg ulcers. J R Soc Med 1991; 84:515.
  114. Baker SR, Stacey MC, Singh G, et al. Aetiology of chronic leg ulcers. Eur J Vasc Surg 1992; 6:245.