Ricardo de Ávila Oliveira1, Rachel Riera2, Vladimir Vasconcelos3, Jose Cc Baptista-Silva4. 1. Surgery, Universidade Federal de Uberlândia, Uberlândia, Brazil. 2. Cochrane Brazil Rio de Janeiro, Cochrane, Petrópolis, Brazil. 3. Department of Surgery, Division of Vascular and Endovascular Surgery, Universidade Federal de São Paulo, São Paulo, Brazil. 4. Evidence Based Medicine, Cochrane Brazil, Universidade Federal de São Paulo, São Paulo, Brazil.
Abstract
BACKGROUND: Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is characterised by oedema, pigmentation, eczema, lipodermatosclerosis, atrophie blanche, and healed or active venous ulcers. Injection sclerotherapy (liquid or foam) is widely used for treatment of varicose veins aiming to transform the varicose veins into a fibrous cord. However, there is limited evidence regarding its effectiveness and safety, especially in patients with more severe disease. This is the second update of the review first published in 2002. OBJECTIVES: To assess the effectiveness and safety of injection sclerotherapy for the treatment of varicose veins. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, and LILACS databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 20 July 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) (including cluster-randomised trials and first phase cross-over studies) that used injection sclerotherapy for the treatment of varicose veins. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed, selected and extracted data. Disagreements were cross-checked by a third review author. We used Cochrane's Risk of bias tool to assess the risk of bias. The outcomes of interest were cosmetic appearance, complications, residual varicose veins, quality of life (QoL), persistence of symptoms, and recurrent varicose veins. We calculated risk ratios (RRs) or mean difference (MD) with 95% confidence intervals (CIs). We used the worst-case-scenario for dichotomous data imputation for intention-to-treat analyses. For continuous outcomes, we used the 'last-observation-carried-forward' for data imputation if there was balanced loss to follow-up. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 23 new RCTs for this update, bringing the total to 28 studies involving 4278 participants. The studies differed in their design, and in which sclerotherapy method, agent or concentration was used. None of the included RCTs compared sclerotherapy to no intervention or to any pharmacological therapy. The certainty of the evidence was downgraded for risk of bias, low number of studies providing information for each outcome, low number of participants, clinical differences between the study participants, and wide CIs. Sclerotherapy versus placebo Foam sclerotherapy may improve cosmetic appearance as measured by IPR-V (independent photography review - visible varicose veins scores) compared to placebo (polidocanol 1%: mean difference (MD) -0.76, 95% CI -0.91 to -0.60; 2 studies, 223 participants; very low-certainty evidence); however, deep vein thrombosis (DVT) rates may be slightly increased in this intervention group (RR 5.10, 95% CI 1.30 to 20.01; 3 studies, 302 participants; very low-certainty evidence). Residual varicose vein rates may be decreased following polidocanol 1% compared to placebo (RR 0.19, 95% CI 0.13 to 0.29; 2 studies, 225 participants; very low-certainty evidence). Following polidocanol 1% use, there may be a possible improvement in QoL as assessed using the VEINES-QOL/Sym questionnaire (MD 12.41, 95% CI 9.56 to 15.26; 3 studies, 299 participants; very low-certainty evidence), and possible improvement in varicose vein symptoms as assessed using the Venous Clinical Severity Score (VCSS) (MD -3.25, 95% CI -3.90 to -2.60; 2 studies, 223 participants; low-certainty evidence). Recurrent varicose veins were not reported for this comparison. Foam sclerotherapy versus foam sclerotherapy with different concentrations Three individual RCTs reported no evidence of a difference in cosmetic appearance after comparing different concentrations of the intervention; data could not be pooled for two of the three studies (RR 1.11, 95% CI 0.84 to 1.47; 1 study, 80 participants; very low-certainty evidence). Similarly, there was no clear difference in rates of thromboembolic complications when comparing one foam concentration with another (RR 1.47, 95% CI 0.41 to 5.33; 3 studies, 371 participants; very low-certainty evidence). Three RCTs investigating higher concentrations of polidocanol foam indicated the rate of residual varicose veins may be slightly decreased in the polidocanol 3% foam group compared to 1% (RR 0.67, 95% CI 0.43 to 1.04; 3 studies, 371 participants; moderate-certainty evidence). No clear improvement in QoL was detected. Two RCTs reported improved VCSS scores with increasing concentrations of foam. Persistence of symptoms were not reported for this comparison. There was no clear difference in recurrent varicose vein rates (RR 0.91, 95% CI 0.62 to 1.32; 1 study, 148 participants; low-certainty evidence). Foam sclerotherapy versus liquid sclerotherapy One RCT reported on cosmetic appearance with no evidence of a difference between foam or liquid sclerotherapy (patient satisfaction scale MD 0.2, 95% CI -0.27 to 0.67; 1 study, 126 participants; very low-certainty evidence). None of the RCTs investigated thromboembolic complications, QoL or persistence of symptoms. Six studies individually showed there may be a benefit to polidocanol 3% foam over liquid sclerotherapy in reducing residual varicose vein rate; pooling data from two studies showed a RR of 0.51, with 95% CI 0.41 to 0.65; 203 participants; very low-certainty evidence. One study reported no clear difference in recurrent varicose vein rates when comparing sodium tetradecyl sulphate (STS) foam or liquid (RR 1.10, 95% CI 0.86 to 1.42; 1 study, 286 participants; very low-certainty evidence). Sclerotherapy versus sclerotherapy with different substances Four RCTs compared sclerotherapy versus sclerotherapy with any other substance. We were unable to combine the data due to heterogeneity or assess the certainty of the evidence due to insufficient data. AUTHORS' CONCLUSIONS: There is a very low to low-certainty evidence that, compared to placebo, sclerotherapy is an effective and safe treatment for varicose veins concerning cosmetic appearance, residual varicose veins, QoL, and persistence of symptoms. Rates of DVT may be slightly increased and there were no data concerning recurrent varicose veins. There was limited or no evidence for one concentration of foam compared to another; foam compared to liquid sclerotherapy; foam compared to any other substance; or one technique compared to another. There is a need for high-quality trials using standardised sclerosant doses, with clearly defined core outcome sets, and measurement time points to increase the certainty of the evidence.
BACKGROUND: Varicose veins are enlarged and tortuous veins, affecting up to one-third of the world's population. They can be a cause of chronic venous insufficiency, which is characterised by oedema, pigmentation, eczema, lipodermatosclerosis, atrophie blanche, and healed or active venous ulcers. Injection sclerotherapy (liquid or foam) is widely used for treatment of varicose veins aiming to transform the varicose veins into a fibrous cord. However, there is limited evidence regarding its effectiveness and safety, especially in patients with more severe disease. This is the second update of the review first published in 2002. OBJECTIVES: To assess the effectiveness and safety of injection sclerotherapy for the treatment of varicose veins. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, and LILACS databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 20 July 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) (including cluster-randomised trials and first phase cross-over studies) that used injection sclerotherapy for the treatment of varicose veins. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed, selected and extracted data. Disagreements were cross-checked by a third review author. We used Cochrane's Risk of bias tool to assess the risk of bias. The outcomes of interest were cosmetic appearance, complications, residual varicose veins, quality of life (QoL), persistence of symptoms, and recurrent varicose veins. We calculated risk ratios (RRs) or mean difference (MD) with 95% confidence intervals (CIs). We used the worst-case-scenario for dichotomous data imputation for intention-to-treat analyses. For continuous outcomes, we used the 'last-observation-carried-forward' for data imputation if there was balanced loss to follow-up. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 23 new RCTs for this update, bringing the total to 28 studies involving 4278 participants. The studies differed in their design, and in which sclerotherapy method, agent or concentration was used. None of the included RCTs compared sclerotherapy to no intervention or to any pharmacological therapy. The certainty of the evidence was downgraded for risk of bias, low number of studies providing information for each outcome, low number of participants, clinical differences between the study participants, and wide CIs. Sclerotherapy versus placebo Foam sclerotherapy may improve cosmetic appearance as measured by IPR-V (independent photography review - visible varicose veins scores) compared to placebo (polidocanol 1%: mean difference (MD) -0.76, 95% CI -0.91 to -0.60; 2 studies, 223 participants; very low-certainty evidence); however, deep vein thrombosis (DVT) rates may be slightly increased in this intervention group (RR 5.10, 95% CI 1.30 to 20.01; 3 studies, 302 participants; very low-certainty evidence). Residual varicose vein rates may be decreased following polidocanol 1% compared to placebo (RR 0.19, 95% CI 0.13 to 0.29; 2 studies, 225 participants; very low-certainty evidence). Following polidocanol 1% use, there may be a possible improvement in QoL as assessed using the VEINES-QOL/Sym questionnaire (MD 12.41, 95% CI 9.56 to 15.26; 3 studies, 299 participants; very low-certainty evidence), and possible improvement in varicose vein symptoms as assessed using the Venous Clinical Severity Score (VCSS) (MD -3.25, 95% CI -3.90 to -2.60; 2 studies, 223 participants; low-certainty evidence). Recurrent varicose veins were not reported for this comparison. Foam sclerotherapy versus foam sclerotherapy with different concentrations Three individual RCTs reported no evidence of a difference in cosmetic appearance after comparing different concentrations of the intervention; data could not be pooled for two of the three studies (RR 1.11, 95% CI 0.84 to 1.47; 1 study, 80 participants; very low-certainty evidence). Similarly, there was no clear difference in rates of thromboembolic complications when comparing one foam concentration with another (RR 1.47, 95% CI 0.41 to 5.33; 3 studies, 371 participants; very low-certainty evidence). Three RCTs investigating higher concentrations of polidocanol foam indicated the rate of residual varicose veins may be slightly decreased in the polidocanol 3% foam group compared to 1% (RR 0.67, 95% CI 0.43 to 1.04; 3 studies, 371 participants; moderate-certainty evidence). No clear improvement in QoL was detected. Two RCTs reported improved VCSS scores with increasing concentrations of foam. Persistence of symptoms were not reported for this comparison. There was no clear difference in recurrent varicose vein rates (RR 0.91, 95% CI 0.62 to 1.32; 1 study, 148 participants; low-certainty evidence). Foam sclerotherapy versus liquid sclerotherapy One RCT reported on cosmetic appearance with no evidence of a difference between foam or liquid sclerotherapy (patient satisfaction scale MD 0.2, 95% CI -0.27 to 0.67; 1 study, 126 participants; very low-certainty evidence). None of the RCTs investigated thromboembolic complications, QoL or persistence of symptoms. Six studies individually showed there may be a benefit to polidocanol 3% foam over liquid sclerotherapy in reducing residual varicose vein rate; pooling data from two studies showed a RR of 0.51, with 95% CI 0.41 to 0.65; 203 participants; very low-certainty evidence. One study reported no clear difference in recurrent varicose vein rates when comparing sodium tetradecyl sulphate (STS) foam or liquid (RR 1.10, 95% CI 0.86 to 1.42; 1 study, 286 participants; very low-certainty evidence). Sclerotherapy versus sclerotherapy with different substances Four RCTs compared sclerotherapy versus sclerotherapy with any other substance. We were unable to combine the data due to heterogeneity or assess the certainty of the evidence due to insufficient data. AUTHORS' CONCLUSIONS: There is a very low to low-certainty evidence that, compared to placebo, sclerotherapy is an effective and safe treatment for varicose veins concerning cosmetic appearance, residual varicose veins, QoL, and persistence of symptoms. Rates of DVT may be slightly increased and there were no data concerning recurrent varicose veins. There was limited or no evidence for one concentration of foam compared to another; foam compared to liquid sclerotherapy; foam compared to any other substance; or one technique compared to another. There is a need for high-quality trials using standardised sclerosant doses, with clearly defined core outcome sets, and measurement time points to increase the certainty of the evidence.
Authors: Lars Rasmussen; Martin Lawaetz; Julie Serup; Lars Bjoern; Bo Vennits; Allan Blemings; Bo Eklof Journal: J Vasc Surg Venous Lymphat Disord Date: 2013-08-03
Authors: Julie Brittenden; Seonaidh C Cotton; Andrew Elders; Emma Tassie; Graham Scotland; Craig R Ramsay; John Norrie; Jennifer Burr; Jill Francis; Samantha Wileman; Bruce Campbell; Paul Bachoo; Ian Chetter; Michael Gough; Jonothan Earnshaw; Tim Lees; Julian Scott; Sara A Baker; Graeme MacLennan; Maria Prior; Denise Bolsover; Marion K Campbell Journal: Health Technol Assess Date: 2015-04 Impact factor: 4.014
Authors: P L Allan; A W Bradbury; C J Evans; A J Lee; C Vaughan Ruckley; F G Fowkes Journal: Eur J Vasc Endovasc Surg Date: 2000-11 Impact factor: 7.069
Authors: C Carroll; S Hummel; J Leaviss; S Ren; J W Stevens; E Everson-Hock; A Cantrell; M Stevenson; J Michaels Journal: Health Technol Assess Date: 2013-10 Impact factor: 4.014