FACTORS ASSOCIATED WITH THE SUCCESS OF SCLEROTHERAPY FOR LOWER-LIMB VARICOSE VEINS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS AND PRIMARY STUDIES

Abstract

Introduction: Sclerotherapy, delivered as liquid, physician-compounded foam (PCF) or proprietary polidocanol endovenous microfoam (PEM), is a guideline-endorsed, low-cost treatment for lower-limb varicose veins, yet its anatomical success is less predictable than that of endovenous thermal ablation. The determinants of success are dispersed across trials and cohorts and have never been synthesised simultaneously across patient, vein and procedural domains. This review aimed to identify the patient-related, vein-related and procedure-related factors associated with successful venous occlusion after sclerotherapy and with recanalisation, recurrence, clinical improvement, retreatment and complications.^1–3

Methods: The study strictly adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. Randomised controlled trials (RCTs) and cohort, case-control, cross-sectional, prospective and retrospective observational studies were eligible. Risk of bias was appraised with RoB 2 for RCTs and the Newcastle–Ottawa Scale (NOS) for observational studies. Occlusion proportions were pooled on the logit scale and comparative effects as risk ratios (RR) using DerSimonian–Laird random-effects models, supplemented by subgroup analyses, meta-regression on follow-up duration, leave-one-out sensitivity analysis, Egger’s test and GRADE certainty ratings.^4–7

Results: Seventy studies (78 reports; 29 RCTs and 41 observational studies; approximately 17,800 patients or limbs) were included. The pooled occlusion rate across 44 treatment arms (4,965/6,023 veins) was 82.7% (95% CI 77.9–86.6), with substantial heterogeneity (I² = 93%). Occlusion declined from 85.7% at ≤3 months to 77.1% beyond 12 months (meta-regression slope −0.16 logit per log-month, p = 0.095). Larger vein diameter was the most consistent adverse factor (7 of 10 studies; e.g., >6 mm, >8 mm and ≥10.2 mm thresholds), followed by obesity (BMI >30 kg/m² HR 3.21), longer treated junctional segment and distal or extensive reflux. PEM achieved higher occlusion than PCF (91.9% vs 80.6%, p < 0.001), catheter-directed delivery outperformed direct-puncture foam (RR 1.38 (95% CI 1.13–1.69)), and 3% polidocanol outperformed 1% in large trunks (HR for failure 2.59 with 1%). Post-procedural compression did not improve occlusion (RR 0.99 (95% CI 0.91–1.07)) but reduced pain and symptoms, and age, sex and gas composition were not consistently associated with occlusion. Foam remained inferior to thermal ablation (RR 0.79 (95% CI 0.66–0.96)). Pooled recurrence was 22.0%, retreatment 23.2%, DVT 1.91% and hyperpigmentation 9.9%.^8–11

Discussion: Sclerotherapy success is chiefly governed by a vein-level “sclerosant dose-to-endothelial-surface” balance: large diameters, long segments and high reflux burden dilute and wash out the sclerosant, whereas catheter delivery, perivenous tumescence, adequate concentration and standardised microfoam concentrate it. Patient factors act mainly through vein calibre and body habitus, while compression chiefly modulates comfort and inflammatory sequelae rather than occlusion. Education level has not been studied as a determinant, representing a clear evidence gap. Certainty was moderate for vein diameter and low or very low for most other factors.^12–14

Conclusion: Vein diameter, body mass index, reflux extent and treated length are the principal predictors of sclerotherapy failure; microfoam, catheter-directed delivery with tumescence and higher polidocanol concentration for larger trunks are the procedural factors most consistently associated with success. Patient selection by diameter (preferentially ≤6–8 mm for PCF), tailored concentration and planned repeat sessions should be incorporated into practice, and standardised prospective multivariable studies—including socio-educational and adherence variables—are recommended.^1,2