Vessel Due F Improves Treatment Outcomes in Varicose Veins in Patients with CEAP C4—C6

Objective. To evaluate the effects of sulodexide (Vessel Due F), endovenous laser ablation (EVLA), and their combination on the dynamics of endothelial dysfunction and venous-specific inflammatory biomarkers in patients with chronic venous disease (CVD) of the lower extremities classified as CEAP C4—C6. Materials and Methods. Ninety-three patients with CVD (CEAP classes C4—C6) were enrolled in the study. Patients were allocated into four groups: (1) compression therapy; (2) EVLA; (3) sulodexide (Vessel Due F) 250 LSU twice daily for 2 months; and (4) EVLA followed by sulodexide at the same dosage. Serum levels of E-selectin, MCP-1, VEGF, MMP-2, and MMP-9 were measured using quantitative enzyme-linked immunosorbent assay at baseline (V0), 2 months (V2), and 12 months (V3). Results. In the compression group, a moderate reduction in E-selectin was observed at 2 months (60.7±2.8 → 56.6±2.5; p<0.01), with no significant difference at 12 months (60.5±2.7; p=0.84). MCP-1, MMP-2, VEGF, and MMP-9 showed no statistically significant changes (p>0.05). In the EVLA group, a marked early decrease in E-selectin (66.2±3.1 → 40.8±2.9; p<0.001) and MCP-1 (231.9±9.8 → 146.3±8.4; p<0.001) was observed, with partial return toward baseline values at 12 months. No significant changes were detected for MMP-2, VEGF, or MMP-9 (p>0.05). In the sulodexide group, MCP-1 (205.4±8.7 → 134.6±7.2; p<0.001) and MMP-2 (421.7±14.8 → 249.0±13.1; p<0.001) significantly decreased at 2 months, with values approaching baseline at 12 months (MCP-1 205.8±8.1; p=0.96; MMP-2 407.2±15.0; p=0.09). MMP-9 significantly decreased both at 2 months (69.2±3.4 → 58.9±3.1; p<0.001) and 12 months (63.8±3.2; p<0.001). E-selectin and VEGF did not change significantly (p>0.05). In the EVLA+sulodexide group, E-selectin significantly decreased at 2 months (67.4±3.5 → 55.8±3.0; p<0.001) and remained reduced at 12 months (55.9±3.1; p<0.001). MCP-1 decreased at 2 months (284.3±11.2 → 203.4±9.6; p<0.001) and remained significantly lower than baseline at 12 months (235.1±10.4; p=0.03). MMP-2 significantly decreased at V2 (529.3±18.6 → 263.8±14.9; p<0.001) with a trend toward persistence at V3 (489.3±17.4; p=0.07). MMP-9 significantly decreased at both time points (74.8±3.9 → 64.8±3.4; p<0.001; and 69.8±3.6; p<0.001). VEGF did not show significant changes at any follow-up time point (p>0.05). Conclusion. Vessel Due F was associated with significant reductions in MCP-1 and matrix metalloproteinases, with the most sustained decreases in MCP-1, E-selectin, MMP-2, and MMP-9 observed in the combined treatment group (EVLA+sulodexide). In patients with CVD classified as CEAP C4—C6, compression therapy demonstrated minimal impact on systemic inflammatory and remodeling biomarkers. EVLA provided a pronounced early reduction in endothelial activation (E-selectin) and inflammatory activity (MCP-1), although partial attenuation of this effect was observed at long-term follow-up. Serum VEGF levels did not change significantly in this cohort.