New Perspectives on Micronised Purified Flavonoid Fraction in Chronic Venous Disease: From Microvalves to Clinical Effectiveness

Abstract

The importance of chronic venous disease (CVD), as a cause of reduced quality of life and increased costs to healthcare systems, is expected to rise in parallel with population aging and the increasing prevalence of obesity. Venoactive drugs (VADs) are frequently used to treat the symptoms and signs of CVD. The most commonly used and widely studied VAD, micronised purified flavonoid fraction (MPFF), is effective at all stages of CVD, and has been shown to significantly reduce leg pain, leg heaviness and swelling, as well as ankle oedema and functional discomfort, in clinical trials. Recently, experiments employing animal models of CVD have demonstrated that MPFF has anti-inflammatory and venotonic effects at the microvalve level, and a pilot clinical study in patients with CVD has provided support for these findings. Collectively, these results suggest that early initiation of MPFF treatment may have the potential to favourably alter the clinical course of the disease, although further clinical data are required to confirm these findings. International guidelines on CVD management strongly recommend MPFF to reduce symptoms and improve quality of life. Studies are now needed to investigate the impact of long-term treatment on disease progression.

Keywords: Animal models; Conservative treatment; Flavonoids; Microvalves; Pharmacological preparations; Varicose ulcer; Varicose veins; Vascular diseases; Veins; Venous insufficiency.

Fig. 1

MPFF treatment significantly attenuated leukocyte adhesion at day 5 post-ligation in a hamster model of venous hypertension, relative to vehicle (10% lactose solution) [9]. Ten hamsters each received either MPFF 100 mg/kg/day per os, vehicle or sham. Treatment was started 2 days before induction of venous hypertension. Comparisons versus vehicle group were post hoc. Horizontal lines indicate median and interquartile range; whiskers indicate minima and maxima. MPFF, micronised purified flavonoid fraction

Fig. 2

Number of sites at which microvalvular reflux was detected in small veins of the lower extremities, using continuous wave Doppler ultrasonography, in 30 patients with symptomatic C₀ (9% of patients) or C₁ (81% of patients) CVD who received MPFF 1000 mg/day [10]. The proportion of sites with reflux was compared at each time point versus baseline using the Pearson’s chi-squared test. CVD, chronic venous disease; MPFF, micronised purified flavonoid fraction

Fig. 3

Mean symptom scores over time in 30 patients with symptomatic C₀ (9% of patients) or C₁ (81% of patients) CVD who received MPFF 1000 mg/day [10]. Bars represent mean values and error bars standard deviation. Paired Student t tests were used to compare baseline and 6-month mean symptom scores. CVD, chronic venous disease; MPFF, micronised purified flavonoid fraction

Fig. 4

Number of patients with CVD symptoms at baseline (V0) and at follow-up (V1) among those prescribed MPFF in the observational VEIN Act Program [24]. CVD, chronic venous disease; MPFF, micronised purified flavonoid fraction. Reprinted by permission from Springer Nature. Drugs and Therapy Perspectives, Management and evaluation of treatment adherence and effectiveness in chronic venous disorders: results of the international study VEIN Act Program. Bogachev V, Arribas JMJ, Baila S, Dominguez JU, Walter J, Maharaj D, et al. © 2019 Drugs & Therapy Perspectives