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 I: symptoms.

INTRODUCTION

Chronic venous disease (CVD) significantly impacts patients' quality of life through leg symptoms and signs. This systematic literature review and meta-analysis, published in two separate articles, evaluated the effects of micronized purified flavonoid fraction (MPFF), a venoactive drug, on CVD symptoms and signs by analyzing data from a wide spectrum of clinical studies in patients with CVD at all stages of the disease. Part I presented herein, focused on symptoms, and Part II on signs.

EVIDENCE ACQUISITION: A systematic review was conducted in November 2023 using PRISMA guidelines. Medline, Embase, and Cochrane databases were searched. Eligible studies included prospective randomized controlled trials (RCTs) and non-RCTs investigating the effects of oral MPFF treatment (1000 mg, daily for at least 1 month) on venous leg symptoms and signs in patients with CVD at all stages (C0s-C6). In the present analysis, primary outcomes were the main venous symptoms including pain, heaviness, discomfort, cramps, feeling of swelling, and burning sensation. Secondary outcomes were pruritus, paresthesia, fatigue, and global symptoms. Patient level of satisfaction with treatment was also assessed. A single-group random-effects meta-analysis was used to estimate the mean change in symptom intensity and the proportion of complete symptom resolution from baseline to the last post-baseline value.

EVIDENCE SYNTHESIS: Out of 387 articles, 56 studies were included in the analysis, among which 51 studies involving 39,878 MPFF-treated patients, reported CVD symptoms. Significant reductions in symptom intensity scores were observed for all outcomes (P<0.001), except for fatigue. Improvement of symptoms was further supported by the resolution of pain, heaviness, cramps, discomfort, and burning sensation observed in pooled estimated proportion of patients (76.2%, 61.5%, 80.5%, 69.8%, and 67.2%, respectively; all P<0.001). The overall level of patient satisfaction was estimated to be more than 90%. Twenty studies had high risk of bias, while sensitivity analyses did not change the study results. Heterogeneity level was frequently high among studies.

CONCLUSIONS

This systematic review and meta-analysis provide strong evidence of consistent and clinically significant improvements in venous leg symptoms associated with the use of the venoactive drug MPFF, across all stages of CVD.