The Effect of Standardized Doses of Hesperidin and Diosmin on Venous Wall Remodeling in Patients with Primary Varicose Veins: a Prospective Controlled Study “STANDARD”

Objective. To study the effect of fixed doses combination of hesperidin and diosmin on venous wall remodeling in patients with primary varicose veins after therapy and endovenous laser ablation (EVLA). Material and methods. A single-center parallel-group prospective controlled study (ClinicalTrials.gov ID: NCT06367166) included 83 patients with varicose veins C2—C3 and 20 healthy volunteers (83 women and 20 men). Subjects were divided depending on treatment strategy: group A — 20 patients received hesperidin (100 mg) and diosmin (900 mg) once a day for 6 months; group B — 20 patients without therapy and invasive treatment; group C — 21 patients received hesperidin (100 mg) and diosmin (900 mg) once a day for 6 months after EVLA; group D — 22 patients underwent EVLA; group E — 20 healthy volunteers. Compression stockings class 2 were prescribed in groups A, B, C and D. We assessed vascular wall remodeling markers using ELISA: von Willebrand factor (vWF), PECAM-1 (CD31), fibronectin (FN), vimentin (VIM), plasminogen activation inhibitor type 1 (PAI-1). Additionally, we studied severity of symptoms using VAS and VCSS scales, as well as quality of life using CIVIQ-20 questionnaire. Results. After 6-month therapy with fixed doses combination of bioflavonoids: hesperidin 100 mg and diosmin 900 mg (VENARUS), we observed more than 6-fold decrease in PAI-1 (p<0.001), more than 22-fold decrease in FN (p<0.001), 2-fold decrease in VIM (p=0.042), 3-fold decrease in vWF (p=0.001) and 1.5-fold decrease in PECAM-1 (p<0.001). EVLA combined with fixed doses combination of bioflavonoids was characterized by more than 9.5-fold decrease in serum PAI-1 (p<0.001), 4.5-fold decrease in FN (p<0.001), 2.5-fold decrease in VIM (p<0.001), 1.8-fold decrease in vWF (p=0.008) and 25% decrease in PECAM-1 (p<0.001) after 6-month therapy. Similar changes were not observed in other groups. The best results regarding severity of symptoms and quality of life were observed after EVLA including postoperative therapy with fixed doses combinations of bioflavonoids. Conclusion. Fixed doses combination of bioflavonoids (hesperidin 100 mg and diosmin 900 mg) contribute to significant changes of venous wall remodeling markers, relief of symptoms and QoL improvement in patients with varicose veins.