title: Pharmacological adjuncts for chronic venous ulcer healing: a systematic review.
abstract: BACKGROUND
  The aim of this study was to systematically review the current evidence and determine whether there is a clinical benefit for using pharmacological agents as adjunctive treatment for chronic venous ulcers.
  
  
  METHODS
  A systematic review of the MEDLINE and EMBASE (from 1 January 1947 through 15 August 2013) and Cochrane databases (from inception through 15 August 2013) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were all randomised controlled trials investigating pharmacological adjuncts for the treatment of venous ulcers with a minimum sample size of 20 patients for each treatment arm.
  
  
  RESULTS
  Ten relevant articles were identified; one pilot randomised controlled trial and four Cochrane reviews were included. Pentoxifylline, aspirin, sulodexide, mesoglycan, flavonoids, thromboxane A2 antagonist (ifetroban), zinc, prostaglandin and prostacyclin analogues were the drugs reviewed. Pentoxifylline was found to be more effective than placebo in terms of complete ulcer healing or in causing a significant improvement (greater than 60% reduction in ulcer size) (RR 1.70, 95% CI 1.30 to 2.24). Aspirin and flavonoids show potential to be effective adjuncts but methodological shortcomings and issues with bias limit the validity of results from trials involving each of these drugs, respectively. There was no significant difference between placebo and Ifetroban and likewise pooled results from trials investigating sulodexide and zinc showed no benefit in comparison to placebo.
  
  
  CONCLUSIONS
  Many systemic pharmacological agents have been investigated as adjuncts to venous ulcer healing; however, pentoxifylline (400 mg, three times a day) is currently the only drug that has promising evidence to support its use. Other compounds are in early stage research.
authors.affiliation: Academic Section of Vascular Surgery, Imperial College London, UK lavanya.varatharajan@gmail.com.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Varatharajan
authors.affiliation: Academic Section of Vascular Surgery, Imperial College London, UK.
authors.forename: Ankur
authors.initials: A
authors.lastname: Thapar
authors.affiliation: Academic Section of Vascular Surgery, Imperial College London, UK.
authors.forename: Tristan
authors.initials: T
authors.lastname: Lane
authors.affiliation: Academic Section of Vascular Surgery, Imperial College London, UK.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Munster
authors.affiliation: Academic Section of Vascular Surgery, Imperial College London, UK.
authors.forename: Alun Huw
authors.initials: AH
authors.lastname: Davies
mesh_terms: D005260:Female; D006801:Humans; D016239:MEDLINE; D008297:Male; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014647:Varicose Ulcer / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D010431:Pentoxifylline
keywords: Chronic venous ulcers; aspirin; pentoxifylline; pharmacological adjuncts