{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:42:35Z","timestamp":1787755355055,"version":"build-2784847793"},"reference-count":19,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Phlebology"],"abstract":"\n Introduction<\/jats:title>\n Venous 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 \u00a33 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This 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,\n ClinicalTrials.gov<\/jats:ext-link>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The 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 \u2013 6.57,\n p<\/jats:italic>\n < .05) and endovenous ablation (OR 2.86, CI 1.19 \u2013 6.88,\n p<\/jats:italic>\n < .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,\n p<\/jats:italic>\n < .05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/02683555261446149","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:43:34Z","timestamp":1776710614000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparing interventions used to treat venous leg ulcers \u2013 A network meta-analysis"],"prefix":"10.1177","author":[{"given":"Shruti","family":"Das","sequence":"first","affiliation":[{"name":"Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7777-6937","authenticated-orcid":false,"given":"Marwah","family":"Salih","sequence":"additional","affiliation":[{"name":"Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5789-0353","authenticated-orcid":false,"given":"Matthew","family":"Tan","sequence":"additional","affiliation":[{"name":"Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-4578","authenticated-orcid":false,"given":"Sarah","family":"Onida","sequence":"additional","affiliation":[{"name":"Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5261-6913","authenticated-orcid":false,"given":"Alun Huw","family":"Davies","sequence":"additional","affiliation":[{"name":"Imperial College London"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"NICE. Leg ulcer - venous: how common is it? (2024) [Available from]: https:\/\/cks.nice.org.uk\/topics\/leg-ulcer-venous\/background-information\/prevalence\/"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2016.25.Sup6.S1"},{"issue":"6","key":"e_1_3_4_4_2","first-page":"026835552413097","article-title":"A systematic review and meta-analysis assessing the impact of pentoxifylline on the healing and recurrence of venous leg ulcers","volume":"40","author":"Salih M","year":"2024","unstructured":"Salih M, Elghazaly H, Salih S, et al. A systematic review and meta-analysis assessing the impact of pentoxifylline on the healing and recurrence of venous leg ulcers. Phlebology: The Journal of Venous Disease 2024; 40(6): 02683555241309797.","journal-title":"Phlebology: The Journal of Venous Disease"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-045253"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/15266028231193978"},{"key":"e_1_3_4_7_2","volume-title":"Overview of management of a person with a venous leg ulcer","author":"NICE","year":"2024","unstructured":"NICE. Overview of management of a person with a venous leg ulcer, 2024. [Available from]: https:\/\/cks.nice.org.uk\/topics\/leg-ulcer-venous\/management\/venous-leg-ulcers\/"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.04.049"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16353-8"},{"issue":"7","key":"e_1_3_4_10_2","first-page":"CD009494","article-title":"Endovenous ablation for venous leg ulcers","volume":"2023","author":"Cai PL","year":"2023","unstructured":"Cai PL, Hitchman LH, Mohamed AH, et al. Endovenous ablation for venous leg ulcers. Cochrane Database Syst Rev 2023; 2023(7): CD009494. https:\/\/doi.org\/10.1002\/14651858.cd009494.pub3","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.12968\/jowc.2018.27.11.758"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-481X.2009.00634.x"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.12814"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2021.12.024"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-019440"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2021.12.024"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.2000.01491.x"},{"issue":"6","key":"e_1_3_4_18_2","first-page":"CD010694","article-title":"Sulodexide for treating venous leg ulcers","volume":"2016","author":"Wu B","year":"2016","unstructured":"Wu B, Lu J, Yang M, et al. Sulodexide for treating venous leg ulcers. Cochrane Database Syst Rev 2016; 2016(6): :CD010694.","journal-title":"Cochrane Database Syst Rev"},{"issue":"5","key":"e_1_3_4_19_2","first-page":"CD006477","article-title":"Flavonoids for treating venous leg ulcers","volume":"2013","author":"Scallon C","year":"2013","unstructured":"Scallon C, Bell-Syer SE, Aziz Z. Flavonoids for treating venous leg ulcers. Cochrane Database Syst Rev 2013; 2013(5): CD006477.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j5157"}],"container-title":["Phlebology: The Journal of Venous Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02683555261446149","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02683555261446149","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02683555261446149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:56:47Z","timestamp":1777658207000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02683555261446149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":19,"alternative-id":["10.1177\/02683555261446149"],"URL":"https:\/\/doi.org\/10.1177\/02683555261446149","relation":{},"ISSN":["0268-3555","1758-1125"],"issn-type":[{"value":"0268-3555","type":"print"},{"value":"1758-1125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"article-number":"02683555261446149"}}