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      Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence

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          Abstract

          Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources; it can also be obtained after conversion of hesperidin extracted from citrus rinds. Micronized purified flavonoid fraction (MPFF) is a preparation that contains mainly diosmin and a small fraction of hesperidin. We performed a state-of-the-art literature review to collect and analyze well-conducted randomized clinical studies comparing diosmin – also called non-micronized or hemisynthetic diosmin – 600 mg a day and MPFF, 1000 mg a day. Three clinical studies met the criteria and were included for this literature review. These clinical studies showed a significant decrease of CVD symptom intensity (up to approximately 50%) and global patient satisfaction after one-to-six-month treatment with diosmin or MPFF, without statistical differences between these two forms of diosmin. Both treatments were well tolerated with few mild adverse drug reactions reported. Overall, based on this literature review, there is no clinical benefit to increase the dose of diosmin beyond 600 mg per day, to use the micronized form, or to add hesperidin, since clinical efficacy on venous symptomatology is achieved with 600 mg per day of pure non-micronized diosmin. This challenges the status of diosmin – 600 mg a day – in guidelines for the management of CVD, which is currently categorized 2C (weak recommendations for use and poor quality of evidence), while the most widely used and assessed preparation MPFF is rated 1B (strong recommendation for use and moderate quality of evidence).

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          Most cited references36

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          Chronic venous insufficiency.

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            CEAP classification system and reporting standard, revision 2020

            The CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification is an internationally accepted standard for describing patients with chronic venous disorders and it has been used for reporting clinical research findings in scientific journals. Developed in 1993, updated in 1996, and revised in 2004, CEAP is a classification system based on clinical manifestations of chronic venous disorders, on current understanding of the etiology, the involved anatomy, and the underlying venous pathology. As the evidence related to these aspects of venous disorders, and specifically of chronic venous diseases (CVD, C2-C6) continue to develop, the CEAP classification needs periodic analysis and revisions. In May of 2017, the American Venous Forum created a CEAP Task Force and charged it to critically analyze the current classification system and recommend revisions, where needed. Guided by four basic principles (preservation of the reproducibility of CEAP, compatibility with prior versions, evidence-based, and practical for clinical use), the Task Force has adopted the revised Delphi process and made several changes. These changes include adding Corona phlebectatica as the C4c clinical subclass, introducing the modifier "r" for recurrent varicose veins and recurrent venous ulcers, and replacing numeric descriptions of the venous segments by their common abbreviations. This report describes all these revisions and the rationale for making these changes.
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              Revision of the CEAP classification for chronic venous disorders: consensus statement.

              The CEAP classification for chronic venous disorders (CVD) was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995. Today most published clinical papers on CVD use all or portions of CEAP. Rather than have it stand as a static classification system, an ad hoc committee of the American Venous Forum, working with an international liaison committee, has recommended a number of practical changes, detailed in this consensus report. These include refinement of several definitions used in describing CVD; refinement of the C classes of CEAP; addition of the descriptor n (no venous abnormality identified); elaboration of the date of classification and level of investigation; and as a simpler alternative to the full (advanced) CEAP classification, introduction of a basic CEAP version. It is important to stress that CEAP is a descriptive classification, whereas venous severity scoring and quality of life scores are instruments for longitudinal research to assess outcomes.
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vasc Health Risk Manag
                vhrm
                vhriskman
                Vascular Health and Risk Management
                Dove
                1176-6344
                1178-2048
                16 September 2021
                2021
                : 17
                : 591-600
                Affiliations
                [1 ]Private Vascular Specialist , Paris, France
                [2 ]Pedagogical Support Office, Faculty of Medicine Pitié-Salpétrière, Sorbonne University , Paris, France
                [3 ]Hospital Albert Einstein , São Paulo, Brazil
                [4 ]Laboratoire Innotech International , Arcueil, France
                Author notes
                Correspondence: Christelle Gouhier-Kodas Email christelle.gouhier-kodas@innothera.com
                Article
                324112
                10.2147/VHRM.S324112
                8455100
                34556990
                3214f4e4-6c4a-4698-871e-a212856dfd45
                © 2021 Cazaubon et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 June 2021
                : 21 August 2021
                Page count
                Figures: 1, Tables: 4, References: 36, Pages: 10
                Categories
                Review

                Cardiovascular Medicine
                chronic venous disorders,venoactive drugs,flavonoids,randomized clinical trials,literature review

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