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Background: The efficacy and tolerability of the new micronized purified flavonoid fraction (MPFF) 1000 mg once-daily chewable formulation in comparison with the established MPFF 500 mg conventional tablet at the same daily dose are unknown., Methods: CHEWY was an international, multicenter, double-blind, double-dummy, randomized, parallel group, non-inferiority phase III study conducted in adult patients with symptomatic chronic venous disease (CVD). Patients were randomly allocated to MPFF 1000 mg chewable or MPFF 2x500 mg daily treatment. The primary efficacy endpoint for clinical non-inferiority (non-inferiority margin predefined at 1 cm) was lower limb discomfort (LLD) assessed by a 10 cm electronic visual analog scale (eVAS) at 8 weeks. Secondary endpoints included leg pain (LP), leg heaviness (LH), and quality of life (QoL) measured by the eCIVIQ-14 questionnaire. Overall acceptability was assessed at each visit by patient and investigator., Results: Three hundred and nine patients were randomized to MPFF 1000 mg chewable and 302 to MPFF 2x500 mg. After 8 weeks, LLD decreased from baseline by -3.6±2.4 cm and -3.6±2.5 cm in the MPFF chewable and 2x500 mg groups, respectively. Non-inferiority of the once-daily chewable formulation compared with twice daily tablets on improving LLD was demonstrated (adjusted between-group difference [Standard Error]) (E [SE]) = 0.00 (0.18) cm, 95%CI -0.35; 0.35, non-inferiority P value <0.0001. Decreases of similar magnitude were observed at 8 weeks for LP and LH in both treatment arms: -3.4±2.3 cm and -3.5±2.5 cm, respectively for LP, and -3.5±2.5 cm and -3.5±2.6 cm, respectively for LH. QoL (global score) improved by -21.0±17.2 and -22.5±20.1 in the MPFF 1000 mg chewable group and 2x500 mg groups, respectively (E [SE]=1.03 [1.20], 95%CI [-1.32; 3.38]), with similar improvements in the QoL subscore components in both groups. Treatment acceptability was high for both patients and physicians and tolerability similar to the tablet formulation., Conclusions: MPFF 1000 mg chewable was non-inferior to MPFF 2x500 mg tablets with respect to its effect on LLD. Both formulations were associated with improvements of similar magnitude in lower limb symptoms and QoL. The chewable formulation was observed to be well tolerated and well accepted. Once-daily MPFF chewable tablet offers patients with CVD a good alternative treatment regimen.

Introduction: Chronic venous disease is a persistent venous drainage alteration caused by valvular incompetence and/or outflow obstruction. Disease management includes a variety of treatments, whose evidence and clinical performance in the mid-long term are variable. The objective of this umbrella review was to summarize efficacy data for pharmacological treatments including venoactive drugs from previously published reviews that included a meta-analytic component., Evidence Acquisition: Systematic database searches were conducted via Ovid SP on 13 August 2019, covering MEDLINE, Embase, and the Cochrane Database of Systematic Reviews. Reviews that included a meta-analytic component of four or more clinical trials or observational studies reporting on the efficacy of systemic or topical pharmacological treatments for adults with chronic venous disease published since 2010 were eligible for inclusion., Evidence Synthesis: Eleven publications were included in this umbrella review. Change in ankle circumference was the most commonly reported outcome. Overall, several systemic treatments had significant effects compared with placebo on multiple efficacy outcomes, including measures of edema and pain. Out of them, Micronized Purified Flavonoid Fraction had the most comprehensive evidence of effectiveness on main symptoms and signs and on improving quality of life throughout chronic venous disease stages., Conclusions: Systemic pharmacotherapies represent a valuable therapeutic option in CVD management. As a result of this umbrella review, several gaps were identified with respect to research topics that warrant further investigation, particularly in the category of topical medications.

Chronic venous disease (CVD) is one of the most prevalent diseases worldwide. The health condition of most patients with early stage CVD will worsen over time, and this progression increases the burden as well as the costs of treatment and reduces patient quality of life (QoL). This highlights the importance and the likely cost-effectiveness of treatment of patients with early stage CVD. Options for managing the early stages of CVD include lifestyle changes together with venoactive drugs (VAD); VADs may be used alone or in conjunction with interventional treatment of varices such as sclerotherapy, surgery, or endovenous treatments. Micronized purified flavonoid fraction (MPFF; Daflon ® ) is a well-studied VAD which has anti-inflammatory activities, reduces endothelial activation and leukocyte adhesion, and increases capillary resistance and integrity, to eventually improve venous tone, CVD symptoms and QoL. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by the author.

Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies., Competing Interests: The authors declare no conflict of interest. The sponsor reviewed a draft of the manuscript but had no role in the decision to publish the final version.