A Literature Review of Pharmacological Agents to Improve Venous Leg Ulcer Healing

Brandon P. Kitchens, DPM, MBA; Robert J. Snyder, DPM, MSc, MBA, CWSP; Cherison A. Cuffy, DPM, CWSP


Wounds. 2020;32(7):195-207. 

In This Article

Abstract and Introduction


Compression therapy is the gold standard treatment for venous leg ulcers (VLUs); however, with adjunctive pharmacological therapies and poor patient adherence using compressive dressings, clinicians are looking to find the advantage in treating VLUs. This literature review focuses on the efficacy of pharmacological agents, quality of life using agents in addition to compression therapy, and cost effectiveness to indicate the best outcomes for pharmacological treatment of VLUs. The following available venotonic, hemorheologic, and fibrinolytic agents were reviewed for oral management in treating VLUs: pentoxifylline, flavonoids (diosmin, hidrosmin, rutosides, and micronized purified flavonoid fraction, Vasculera), Red-Vine-Leaf-Extract AS 195, Ruscus, Ginkgo biloba, Centella asiatica, Pycnogenol (French maritime pine bark), escin/horse chestnut extract, nutritional supplements (ie, zinc and magnesium, glycosaminoglycans [sulodexide], mesoglycans), Axaven, cilostazol, fibrinolytic enhancers (stanozolol and defibrotide), calcium dobesilate, aspirin, antibiotics (antimicrobials, doxycycline, levamisole), diuretics, cinnarizine, naftazone, and benzarone. Venous leg ulcer pharmacological treatment options were searched in the English language from February 2020 to March 2020 using numerous databases and sites, such as PubMed. Drugs used adjunctively with compression therapy that facilitate healing in long-standing or large VLUs include micronized purified flavonoid fraction, pentoxifylline, sulodexide, and mesoglycan.


Venous leg ulcers (VLUs), or varicose ulcers, are the final stage of chronic venous insufficiency (CVI) and are the most common type of leg ulcer.[1] The development of VLUs on distal legs and ankles can occur after minor trauma or spontaneously. The ulcers are often painful and exudative, healing is often long-drawn-out, and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, health care, and socioeconomic costs.[1] Venous leg ulcers are a common and costly problem worldwide; prevalence of VLUs is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older.[1] In addition, the recurrence rates within 3 months of healing are reported to be about 70%.[2] Venous leg ulcers can cultivate physical, financial, and psychological implications, such as pain and disability,[3] depression,[4,5] social isolation,[5] and decreased quality of life.[6] Venous leg ulcers account for approximately 2% to 3% of total health care expenditure in developed countries.[7] The main treatment for a VLU is a firm compression dressing. Compression assists by reducing venous hypertension, thus reducing peripheral edema and enhancing venous return. However, studies show compression only has moderate effects on healing, with up to 50% of VLUs remaining unhealed after 2 years of compression therapy.[1] Adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor. Pharmacological treatment that suppresses inflammation and reduces the frequency of VLUs would be an invaluable intervention to complement compression treatments.

The objective of this review is to provide pharmaceutical options for treatments of VLUs based on the current literature.