Comparing interventions used to treat venous leg ulcers - A network meta-analysis

IntroductionVenous leg ulcers (VLUs) account for up to 80% of chronic lower limb ulcers. The management of these ulcers is complex and can involve multiple interventions, ranging from compression, to pharmacotherapy, surgical and endovenous procedures. Despite these, VLUs are associated with prolonged healing times and high recurrence rates. They therefore pose a significant burden to both patients and the healthcare system, costing the National Health Service over £3 billion annually. Previous studies have largely compared interventions with standard of care rather than against each other. Due to a lack of head-to-head comparisons, this network meta-analysis is necessary to establish which adjunctive intervention, when combined with compression therapy, is most effective in healing VLUs.MethodsThis network meta-analysis was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PRISMA for Network Meta-Analyses (PRISMA-NMA) extension. A comprehensive search algorithm identified all relevant human studies published in English across MEDLINE, EMBASE, ClinicalTrials.gov and PubMed databases. This study included only randomised controlled trials reporting on complete venous leg ulcer healing rates at 24 weeks on patients over the age of 18 years. Two independent authors screened and reviewed all articles for inclusion and performed data extraction.ResultsThe search resulted in 2,237 papers. Of these, 15 randomised controlled trials met the inclusion criteria, enrolling a total of 2,571 patients. Four studies evaluated pentoxifylline, three looked at ablation, three studied sclerotherapy, two evaluated surgery, one studied aspirin, one focused on flavonoids and one on ultrasound therapy. All studies employed these interventions as an adjunct to compression. Both pentoxifylline (OR 3.1, CI 1.46 - 6.57, p < .05) and endovenous ablation (OR 2.86, CI 1.19 - 6.88, p < .05) were shown to significantly improve ulcer healing at 24 weeks when compared to compression monotherapy. No other interventions demonstrated a statistically significant improvement in ulcer healing. Heterogeneity was moderate across the studies (I2 = 66.4%) and there was moderate inconsistency in the network (Q score = 20.82, p < .05).ConclusionsThe results demonstrate the potential for pentoxifylline and endovenous ablation to have a significant beneficial impact on ulcer healing. However, the results should be interpreted with a degree of caution given the moderate heterogeneity and inconsistency. Further large-scale randomised controlled trials evaluating interventions in head-to-head comparisons are needed in the future.