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New Perspectives on Micronised Purified Flavonoid Fraction in Chronic Venous Disease: From Microvalves to Clinical Effectiveness (2022)
Eliete Bouskela . Marzia Lugli . Andrew Nicolaides
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, micronized 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 edema 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 favorably 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.
INTRODUCTION
Chronic venous disease (CVD) is a progressive condition associated with a significant burden for individuals, families, societies, and healthcare systems [1, 2]. This burden is projected to increase in the coming decades, in association with population aging and rising levels of obesity [3]. Although symptoms and signs can be present early on, the disease is particularly debilitating and costly in patients with advanced disease and venous leg ulceration [2]; thus, there is an urgent need for interventions that can prevent or slow the progression of CVD.
The cornerstones of conservative treatment for CVD are compression and venoactive drug (VAD) therapy [4]. Surgical options, including endovascular interventions and sclerotherapy, may be offered as the disease progresses. However, the principal aim of all these interventions is, at present, reactive—i.e. to reduce symptoms and signs, resolve functional impairments, improve quality of life (QoL) and promote the healing of established ulcers—as opposed to proactive measures that halt or slow disease progression.
Micronised purified flavonoid fraction (MPFF)—consisting of 90% diosmin and 10% concomitant active flavonoids, including hesperidin, linarin, and isorhoifolin—is the most widely prescribed VAD for the treatment of CVD in Europe [5], and is also available as an over-the-counter product in several countries. Recent discoveries in animal models and in patients with CVD have suggested that MPFF may have the potential to alter the clinical course of CVD [6–10]. These and other findings were the subject of an industry-sponsored symposium, titled ‘‘Chronic or not: a disorder for life?’’, which was held virtually on 24 June 2021 as part of the 21st Annual Meeting of the European Venous Forum, and the scientific content of which is summarised in this article. Discussion of other venoactive drugs is beyond the scope of this article. Further, this article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
*MPFF IN EXPERIMENTAL ANIMAL MODELS OF VENOUS HYPERTENSION
*MICROVALVULAR EFFECTS OF MPFF IN SYMPTOMATIC CVD
*RECENT CLINICAL STUDIES OF MPFF IN CVD
Overall, the evidence base that supports the clinical use of MPFF in CVD is both more comprehensive (i.e. demonstrating benefits in a wider range of signs and symptoms) and more robust than the evidence for other VADs such as Ruscus and oxerutins [4]. Additionally, MPFF has been shown to significantly improve QoL. Consequently, the most recent guidelines on the use of VADs strongly endorse MPFF for the treatment of most signs and symptoms of CVD (Table 1).
CONCLUSIONS
MPFF has a number of well-established mechanisms of action that make it an effective treatment for various symptoms associated with all stages of CVD; as a result, it is strongly recommended by international guidelines on VAD treatment [4]. Recent evidence has shown that its beneficial effects may be mediated, at least in part, via inhibition of leukocyte adhesion, improvements in venous tone and valvular competence, and reductions in reflux. These findings suggest that, in addition to alleviating symptoms and improving QoL, MPFF could potentially slow CVD progression. In the future, studies assessing early initiation of, and long-term treatment with, MPFF to prevent CVD, delay downstream events (e.g. venous leg ulceration and surgery), and/or improve socioeconomic outcomes (e.g. employment, productivity, social functioning, and QoL) will generate valuable new insights.
Eliete Bouskela . Marzia Lugli . Andrew Nicolaides
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, micronized 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 edema 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 favorably 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.
INTRODUCTION
Chronic venous disease (CVD) is a progressive condition associated with a significant burden for individuals, families, societies, and healthcare systems [1, 2]. This burden is projected to increase in the coming decades, in association with population aging and rising levels of obesity [3]. Although symptoms and signs can be present early on, the disease is particularly debilitating and costly in patients with advanced disease and venous leg ulceration [2]; thus, there is an urgent need for interventions that can prevent or slow the progression of CVD.
The cornerstones of conservative treatment for CVD are compression and venoactive drug (VAD) therapy [4]. Surgical options, including endovascular interventions and sclerotherapy, may be offered as the disease progresses. However, the principal aim of all these interventions is, at present, reactive—i.e. to reduce symptoms and signs, resolve functional impairments, improve quality of life (QoL) and promote the healing of established ulcers—as opposed to proactive measures that halt or slow disease progression.
Micronised purified flavonoid fraction (MPFF)—consisting of 90% diosmin and 10% concomitant active flavonoids, including hesperidin, linarin, and isorhoifolin—is the most widely prescribed VAD for the treatment of CVD in Europe [5], and is also available as an over-the-counter product in several countries. Recent discoveries in animal models and in patients with CVD have suggested that MPFF may have the potential to alter the clinical course of CVD [6–10]. These and other findings were the subject of an industry-sponsored symposium, titled ‘‘Chronic or not: a disorder for life?’’, which was held virtually on 24 June 2021 as part of the 21st Annual Meeting of the European Venous Forum, and the scientific content of which is summarised in this article. Discussion of other venoactive drugs is beyond the scope of this article. Further, this article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
*MPFF IN EXPERIMENTAL ANIMAL MODELS OF VENOUS HYPERTENSION
*MICROVALVULAR EFFECTS OF MPFF IN SYMPTOMATIC CVD
*RECENT CLINICAL STUDIES OF MPFF IN CVD
Overall, the evidence base that supports the clinical use of MPFF in CVD is both more comprehensive (i.e. demonstrating benefits in a wider range of signs and symptoms) and more robust than the evidence for other VADs such as Ruscus and oxerutins [4]. Additionally, MPFF has been shown to significantly improve QoL. Consequently, the most recent guidelines on the use of VADs strongly endorse MPFF for the treatment of most signs and symptoms of CVD (Table 1).
CONCLUSIONS
MPFF has a number of well-established mechanisms of action that make it an effective treatment for various symptoms associated with all stages of CVD; as a result, it is strongly recommended by international guidelines on VAD treatment [4]. Recent evidence has shown that its beneficial effects may be mediated, at least in part, via inhibition of leukocyte adhesion, improvements in venous tone and valvular competence, and reductions in reflux. These findings suggest that, in addition to alleviating symptoms and improving QoL, MPFF could potentially slow CVD progression. In the future, studies assessing early initiation of, and long-term treatment with, MPFF to prevent CVD, delay downstream events (e.g. venous leg ulceration and surgery), and/or improve socioeconomic outcomes (e.g. employment, productivity, social functioning, and QoL) will generate valuable new insights.
