PMID- 29478266 OWN - NLM STAT- MEDLINE DCOM- 20180322 LR - 20221130 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 2 IP - 2 DP - 2018 Feb 25 TI - Treatment for superficial thrombophlebitis of the leg. PG - CD004982 LID - 10.1002/14651858.CD004982.pub6 [doi] LID - CD004982 AB - BACKGROUND: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007. OBJECTIVES: To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein. DATA COLLECTION AND ANALYSIS: Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects. AUTHORS' CONCLUSIONS: Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments. FAU - Di Nisio, Marcello AU - Di Nisio M AD - Department of Medicine and Ageing Sciences, University "G. D'Annunzio" of Chieti-Pescara, Via dei Vestini 31, Chieti Scalo, Italy, 66013. FAU - Wichers, Iris M AU - Wichers IM FAU - Middeldorp, Saskia AU - Middeldorp S LA - eng GR - ETM/442/CSO_/Chief Scientist Office/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20180225 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Anticoagulants) RN - 0 (Factor Xa Inhibitors) RN - 0 (Heparin, Low-Molecular-Weight) RN - 0 (Polysaccharides) RN - 9NDF7JZ4M3 (Rivaroxaban) RN - J177FOW5JL (Fondaparinux) SB - IM UOF - Cochrane Database Syst Rev. 2013 Apr 30;(4):CD004982. PMID: 23633322 CIN - Br J Community Nurs. 2019 Jun 2;24(6):263-264. PMID: 31166771 MH - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use MH - Anticoagulants/*therapeutic use MH - Factor Xa Inhibitors/therapeutic use MH - Fondaparinux MH - Hemorrhage/chemically induced MH - Heparin, Low-Molecular-Weight/*therapeutic use MH - Humans MH - Polysaccharides/therapeutic use MH - Randomized Controlled Trials as Topic MH - Rivaroxaban/therapeutic use MH - Stockings, Compression MH - Thrombectomy MH - Thromboembolism/prevention & control MH - Thrombophlebitis/drug therapy/surgery/*therapy MH - Venous Thromboembolism/*prevention & control PMC - PMC6953389 COIS- MDN: Dr Di Nisio reported participation to Advisory Boards for Daiichi-Sankyo and Pfizer, and receiving consultancy fees from Daiichi-Sankyo and Bayer Health Care.
 IW: none known.
 SM: Dr Middeldorp was a member of the Steering Committee of the CALISTO study, which was funded by GlaxoSmithKline (GSK) and which investigated the efficacy and safety of fondaparinux for superficial thrombophlebitis; funds were paid to Dr Middeldorp's institution. Dr Middeldorp's institution had also received funding from several pharmaceutical companies, including GSK, BMS, Bayer, Boehringer Ingelheim, Sanofi, and Pfizer to support some of her other educational and research activities. The first version of this review was written before the CALISTO study was designed. EDAT- 2018/02/27 06:00 MHDA- 2018/03/23 06:00 PMCR- 2019/02/25 CRDT- 2018/02/26 06:00 PHST- 2018/02/27 06:00 [pubmed] PHST- 2018/03/23 06:00 [medline] PHST- 2018/02/26 06:00 [entrez] PHST- 2019/02/25 00:00 [pmc-release] AID - CD004982.pub6 [pii] AID - 10.1002/14651858.CD004982.pub6 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2018 Feb 25;2(2):CD004982. doi: 10.1002/14651858.CD004982.pub6.