A Systematic Review Network Meta-Analysis and Meta-Regression on Surgical and Endovenous Interventions for the Treatment of Lower Limb Venous Ulcer Disease
Authors: Bontinis Vangelis , Ktenidis Kiriakos , Bontinis Alkis , Koutsoumpelis Andreas , Antonopoulos Constantine N , Giannopoulos Argirios , Rafailidis Vasileios , Chorti Angeliki , Bradbury Andrew W 
Published: August 2023

Background: Venous leg ulcer (VLU) disease constitutes the most severe form of chronic venous insufficiency. We performed a network meta-analysis and meta-regression to investigate the efficacy and safety of the various available interventions in the treatment of VLU. Methods: We conducted a systematic research corresponding to the instructions by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for studies reporting on surgical or endovenous interventions for the treatment of VLU. Following data extraction, we performed a Bayesian network meta-analysis and meta-regression. Primary endpoints included VLU healing and recurrence. The secondary endpoint was postintervention complications. Results: Seventeen studies evaluating the impact of compression monotherapy, radiofrequency ablation (RFA), endovenous laser ablation (EVLA), sclerotherapy, and saphenous vein surgery on VLU treatment, consisting of 2156 patients (2186 VLU) were included. When compared to compression monotherapy, RFA was the only treatment displaying a statistically-significant impact on ulcer healing, odds ratio (OR) 5.80 (95% credibility interval (CI): 1.08–35.07), while EVLA, RR 0.06 (95% CI: 0.00–0.57), sclerotherapy, RR 0.07 (95% CI: 0.00–0.68) and RFA, RR 0.12 (95% CI: 0.01–0.91) were the 3 interventions reducing VLU recurrence. EVLA (SUCRA, 69.65) ranked as the most efficient intervention concerning ulcer recurrence reduction. Regarding postintervention complications, EVLA was the only intervention displaying a statistically-significant increased risk compared to compression monotherapy, RR 14.3 (95% CI: 2.03–172.56). Meta-regression analysis exploring the impact of perforator treatment on VLU failed to predict healing, β = −0.27 (95% CI: −2.55 to 1.85), recurrence, β = −0.02 (95% CI: −2.96 to 2.75) and complication outcomes, β = −0.089 (95% CI: −3.13 to 2.85). During sensitivity analysis, RFA and sclerotherapy failed to sustain their effects on ulcer healing and ulcer recurrence, respectively. In addition, sclerotherapy displayed statistically-significant inferior outcomes compared to both EVLA and RFA regarding ulcer recurrence. Conclusion: This is the first network meta-analysis examining the effect of various interventions on VLU disease. While we have demonstrated the efficacy of RFA and ELVA in ulcer recurrence prevention, our results regarding the impact of RFA and sclerotherapy on VLU healing and recurrence, respectively, should be interpreted with caution. In addition, this review raises questions concerning the value of surgery and perforator interventions in the treatment of VLU. Further research through randomized controlled trials is required. Clinical impact Our review has revealed the significant efficacy of endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in effectively reducing the incidence of ulcer recurrence when compared to compression monotherapy. These outcomes hold the potential to provide relevant insights to both medical practitioners and patients, thereby informing a more prudent and enlightened decision-making approach. Such informed decisions, aimed at mitigating the recurring occurrence of venous leg ulcers, carry profound significance given the considerable socioeconomic implications associated with this medical condition.