Effectiveness of micronized purified flavonoid fraction on venous symptoms and signs in patients at all stages of chronic venous disease: A systematic review and meta-analysis. Part II: signs.

INTRODUCTION

Chronic venous disease (CVD) is a widespread disease characterized by various clinical manifestations. This manuscript is Part II of a systematic literature review and meta-analysis assessing the effects of micronized purified flavonoid fraction (MPFF) on lower limb symptoms and signs in patients with CVD at all stages of the disease. Part I examined symptoms and Part II presented herein focused on signs.

EVIDENCE ACQUISITION: A systematic literature review was conducted in November 2023 to identify studies investigating the efficacy of MPFF oral treatment (1000 mg daily for at least 1 month) on venous symptoms and signs in patients with CVD at all stages (C0s-C6). Databases searched included Medline, Embase, and Cochrane. Eligible studies included randomized controlled trials (RCTs) and non-RCTs (non-randomized comparative, single-arm, and observational studies) evaluating venous signs: edema, redness, ulcer healing and disease severity assessed by venous clinical severity score (VCSS). A single-group random-effects meta-analysis was used to estimate the mean change in sign intensity and the proportion of sign improvement or complete resolution from baseline to the final assessment.

EVIDENCE SYNTHESIS: Out of 387 identified articles, 56 studies were included in the analysis, among which 33 reported CVD signs in 24,617 MPFF-treated patients. Included participants were mainly females (84.1%) with a mean age (±SD) of 48.6 (±8.8) years, and overweight with a mean BMI of 26.3 (±4.5) kg/m2. Significant reductions were observed in mean [95% confidence interval] ankle and calf circumferences (-7.6 mm [-9.1 to -6.2] and -8.0 mm [-11.2 to -4.8], respectively, P<0.001). Venous ulcers were healed in 48.9% [30.3% to 67.8%] or regressed in 73.4% [63.3% to 82.3%] of the patients (P<0.001). Significant improvements were also shown in redness and VCSS score (P<0.001). Twelve studies had a high risk of bias, while sensitivity analyses did not change the study results. Heterogeneity level was frequently high among studies.

CONCLUSIONS

This comprehensive meta-analysis provides additional evidence supporting the effectiveness of MPFF in improving clinical signs of CVD across all stages of the disease.