Effectiveness of herbal drug Terminalia Arjuna in chronic venous insufficiency - A prospective observational study.

INTRODUCTION: Chronic venous insufficiency (CVI) manifests in various clinical presentations ranging from asymptomatic but cosmetic problems to severe symptoms, such as lower limb edema, skin trophic changes, and ulceration. CVI substantially affects the quality of life and work productivity of the patients. Ayurveda, an ancient traditional medicine in India, evaluates the various pathological stages of CVI with a wide range of pathological conditions such as Siragranthi (venous abnormalities), Raktavaritavata (disorders of vata occluded by rakta ∼ blood), ApanaVaigunya (vitiated apanavayu), Arsha (hemorrhoids), VataRakta (rheumatism due to rakta), Kushtha (integumentary disease) and Dushta Vrana (putrefied wound) depending upon the presentations of the patient. Ayurvedic texts mention Terminalia arjuna as a potential herb for treating various conditions related to the circulatory system. The drug is an effective anti-inflammatory, anti-oxidant, and anti-hypertensive and has a definite role in improving cardiovascular hemodynamics and wound healing. These attributes suggest that the potential of Terminalia arjuna needs to be explored as a promising venoactive drug. METHODS: This prospective observational study included 25 patients (31 limbs) with CVI who were treated with Tab Terminalia arjuna (Bark extract of Terminalia arjuna in a dose of 500 mg, given twice a day) and were observed on two visits on day 30 and day 90. Follow-up was carried out for three months to evaluate post-treatment complications or adverse effects. The clinical outcome assessment was done using Venous Clinical Severity Score (VCSS), and clinical grading was performed using clinical classification (C0 - C6) of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification. RESULTS: The median VCSS score (of both limbs) during the third visit was comparatively lower than the first, with a statistically significant improvement at 0.05 level. Further, there was a substantial positive improvement in the clinical classification of CEAP among the patients in pre and post treatment phase. CONCLUSION: The prospective observational study shows that Tab Terminalia arjuna is safe and effective in CVI, reducing the symptoms like pain, edema, inflammation, pigmentation, induration and also expediting ulcer healing.

Development and validation of the Baseline Recurrence Risk in Cellulitis (BRRISC) score.

OBJECTIVES: Cellulitis is often treated with antibiotics for longer than recommended by guidelines. Prolonged therapy may reduce recurrence in certain patients, but it is not known which patients are at greatest risk. Our objective was to develop and temporally validate a risk prediction score to identify patients attending hospital with cellulitis at highest risk of recurrence. METHODS: We included UK adult patients with cellulitis attending hospital in an electronic health records (EHR) study to identify demographic, comorbid, physiological, and laboratory factors predicting recurrence (before death) within 90 days, using multivariable logistic regression with backwards elimination in complete cases. A points-based risk score integerised model coefficients for selected predictors. Performance was assessed using the C-index in development and temporal validation samples. RESULTS: The final model included 4938 patients treated for median 8 days (IQR 6-11); 8.8% (n = 436) experienced hospitalisation-associated recurrence. A risk score using eight variables (age, heart rate, urea, platelets, albumin, previous cellulitis, venous insufficiency, and liver disease) ranged from 0-15, with C-index = 0.65 (95%CI: 0.63-0.68). Categorising as low (score 0-1), medium (2-5) and high (6-15) risk, recurrence increased fourfold; 3.2% (95%CI: 2.3-4.4%), 9.7% (8.7-10.8%), and 16.6% (13.3-20.4%). Performance was maintained in the validation sample (C-index = 0.63 (95%CI: 0.58-0.67)). Among patients at high risk, four distinct clinical phenotypes were identified using hierarchical clustering 1) young, acutely unwell with liver disease; 2) comorbid with previous cellulitis and venous insufficiency; 3) chronic renal disease with severe renal impairment; and 4) acute severe illness, with substantial inflammatory responses. CONCLUSIONS: Risk of cellulitis recurrence varies markedly according to individual patient factors captured in the Baseline Recurrence Risk in Cellulitis (BRRISC) score. Further work is needed to optimise the score, considering baseline and treatment response variables not captured in EHR data, and establish the utility of risk-based approaches to guide optimal antibiotic duration.

Cardiovascular Insights for the Appropriate Management of Chronic Venous Disease: A Narrative Review of Implications for the Use of Venoactive Drugs.

Evidence suggests that chronic venous disease (CVD) may be a cardiovascular disorder, as patients with CVD are prone to developing arterial (atherosclerosis) and venous (thromboembolism) diseases. This may be partly explained by shared risk factors. Thus, patients with CVD or cardiovascular disease require careful history-taking and physical assessment to identify coexisting pathologies and risk factors. This article summarises a symposium at the XIX World Congress of the International Union of Phlebology held in Istanbul, Turkey, in September 2022. Common pathophysiological features of CVD and cardiovascular disease are endothelial injury, hypercoagulability and systemic inflammation. In CVD, inflammation primarily affects the microcirculation, with changes in capillary permeability, vein wall and valve remodelling and increase in oxidative stress. Once patients develop symptoms/signs of CVD, they tend to reduce their physical activity, which may contribute to increased risk of cardiovascular disease. Data show that the presence of CVD is associated with an increased risk of cardiovascular disease, including peripheral arterial disease and heart failure (HF), and the risk of adverse cardiovascular events increases with CVD severity. In addition, patients with cardiovascular disease, particularly those with HF, are at increased risk of venous thromboembolism (VTE) and should be assessed for VTE risk if they are hospitalised with cardiovascular disease. Therefore, CVD management must include a multi-specialty approach to assess risk factors associated with both the venous and arterial systems. Ideally, treatment should focus on the resolution of endothelial inflammation to control both CVD and cardiovascular disease. International guidelines recommend various conservative treatments, including venoactive drugs (VADs), to improve the symptoms/signs of CVD. Micronized purified flavonoid fraction (MPFF) is a VAD, with high-quality evidence supporting its use in relieving symptoms/signs of CVD and improving quality of life. Moreover, in large-scale observational studies, MPFF has shown superior effectiveness in real-world populations compared with other VADs. Video Abstract. (MP4 97173 kb).

Blood vessel disease can affect both arteries and veins; when it affects arteries, it is called cardiovascular disease, and when it affects veins, it is called chronic venous disease (CVD). In most cases, the underlying disease process is similar, irrespective of the type of blood vessels affected, and the risk of both CVD and cardiovascular disease is increased by age, smoking, overweight/obesity and diabetes. If cardiovascular disease affects arteries in the legs, the symptoms can be similar to that of CVD, with pain, feelings of leg heaviness or tiredness and skin changes. CVD and cardiovascular disease are usually treated by different specialists. A symposium was held at the XIX World Congress of the International Union of Phlebology in Istanbul, Turkey, in September 2022, to raise awareness of the relationship between the two conditions. The speakers described the common disease processes in CVD and cardiovascular disease, and how patients with CVD are at increased risk of cardiovascular disease, and vice versa. They reiterated the importance of thoroughly assessing patients with either cardiovascular disease or CVD to see if both arterial and venous disease were present. When patients have CVD, international treatment guidelines recommend various conservative treatments, including venoactive drugs, to improve symptoms and signs. There is high-quality evidence to support the use of the venoactive drug, micronized purified flavonoid fraction (MPFF), to improve quality of life and relieve a broad range of CVD symptoms/signs. Large-scale observational studies support the effectiveness of MPFF in a real-world population of patients with CVD compared with other venoactive drugs.

VEIN STEP: A Prospective, Observational, International Study to Assess Effectiveness of Conservative Treatments in Chronic Venous Disease.

INTRODUCTION: VEIN STEP was conducted to collect international data on the management of chronic venous disease (CVD) and to assess the effectiveness of conservative treatments for the relief of CVD signs and symptoms. METHODS: This international, observational, prospective, longitudinal, cohort study recruited adult outpatients consulting for symptomatic CVD. The primary objective was the effectiveness of conservative treatments on symptoms, signs and quality of life in a real-life setting assessed using a range of patient-reported outcome measures: 10-cm Visual Analog and Patient Global Impression of Change scales for symptoms; Venous Clinical Severity Score for physician assessment of signs; and 14-item ChronIc Venous Insufficiency Questionnaire (CIVIQ-14) for quality of life. At inclusion, patients were prescribed conservative treatment according to the physicians' usual practice. Follow-up visits took place at weeks 2 and 4, with an optional week 8 visit. RESULTS: The analysis set comprised 6084 subjects (78% female) from nine countries with a mean age of 50.6 ± 13.8 years and BMI of 28.0 ± 4.9 kg/m2. The most common CEAP classifications were C1 (23.0%), C2 (31.6%), and C3 (30.7%). Conservative therapy consisted of oral venoactive drugs (VADs; 95.8% of subjects) including micronized purified flavonoid fraction (MPFF 75.5%) and diosmin (18.8%), compression (52.0%), and topicals (31.5%). Conservative therapy led to global symptom improvement in 89% of patients after 2 weeks and 96% at 4 weeks. Pain, leg heaviness, cramps, and sensation of swelling were improved in 82%, 71%, 45.5%, and 46% of patients, respectively. Conservative therapy was associated with a decrease over time in patient-assessed global symptom intensity: - 2.37 ± 1.73 (P < 0.001) and physician-assessed disease severity - 1.83 ± 2.82 (P < 0.001). Among the VADs, MPFF-based conservative therapy was associated with the greatest reduction in symptom and sign intensity. Improvements in CIVIQ-14 were observed with all treatments but were greatest for MPFF. CONCLUSION: In this prospective study conducted in the real-world setting, treatment with conservative therapy, in particular MPFF, was associated with meaningful improvements in the clinical signs and symptoms of disease as well as in quality of life in patients with CVD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04574375.

STUDY AIM: The VEIN STEP study aimed to gather global data on managing chronic venous disease (CVD) and evaluate the usefulness of conservative (non-surgical) treatments for improving CVD signs and symptoms. METHODS: Persons included in the study group had symptomatic CVD and were visiting outpatient clinics. The main aim was to measure how well treatments improved symptoms, physical signs of the illness, and quality of life. Different methods were used to measure these aspects, such as rating symptoms on a 10-point scale and using questionnaires completed by patients and doctors. STUDY FINDINGS: 6084 participants from nine countries joined the study. They were mostly women (78%) with an average age of around 50. Common symptoms included leg pain and leg heaviness. Treatments consisted mainly of drugs active on vein function, like MPFF and diosmin, along with compression stockings and creams. Conservative treatment led to symptom improvement in 89% of patients after 2 weeks and 96% at 4 weeks. Pain and leg heaviness improved in most patients (82% and 71% over the same period) while cramps, and swelling showed improvement in 45.5% and 46% of patients, respectively. Patients reported a significant decrease in symptom intensity, and doctors observed a reduction in disease severity. MPFF was associated with the highest reduction in symptom intensity. Improvements in quality of life were observed with all treatments but were greatest for MPFF. CONCLUSION: The study highlights that conservative treatments, especially MPFF, are associated with significant improvements in the clinical signs and symptoms of patients with CVD as well as in their quality of life.

Xioglican Cream in Italian Patients with Chronic Venous Disease: A Post-Marketing Study Investigating Effects on Clinical and Cutaneous Signs and Symptoms.

INTRODUCTION: The progression of chronic venous disease (CVD) is characterized by edema of the legs and/or venous ulcers of the lower limbs in association with cutaneous signs and/or skin alterations, such as hyperpigmentation, corona phlebectatica, telangiectasia, eczematous dermatitis, lipodermatosclerosis, atrophie blanche, cellulitis, and induration. Xioglican cream is a galactosaminoglycan polysulfate and hyaluronic acid-containing medical device with strong hydrophilic, moisturizing, and soothing properties. This post-marketing observational study evaluated topical Xioglican cream in the amelioration of skin manifestations and clinical signs and symptoms in patients with CVD treated in routine clinical practice. METHODS: Adult patients (18-75 years) with a clinical diagnosis of C2-C3 CVD according to Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification who received 12 weeks of treatment with Xioglican (applied up to 3 times daily), according to investigator decision (and consistent with conventional clinical practice and established standard of care), were enrolled from two study sites in Italy. A range of endpoints were used to evaluate efficacy, safety, effect on patient quality of life (QoL), and patient satisfaction with topical application of Xioglican cream in the physiological restoration of skin signs and symptoms. RESULTS: In patients with CVD (n = 30), Xioglican cream reduced CVD-related skin manifestations and associated symptoms, with significant reductions in leg circumference [mean ± standard deviation (SD): - 3.21 ± 3.39 cm for left and - 2.92 ± 2.70 cm for right legs, both p < 0.0001] and local edema (- 5.52 ± 7.94 cm, p = 0.0034) and significant improvement in Venous Clinical Severity Scores (mean 0.52 ± 1.94 decrease from baseline, p = 0.1952) observed after 12 weeks. Skin burning, pain, aching or tiredness, and QoL were also significantly improved. There was no change in CEAP classification. Globally, 92.0% of patients were "Very satisfied" or "Satisfied" with the product. CONCLUSIONS: Topical treatment with Xioglican cream improves the signs, symptoms, and QoL of patients with CVD class C2-C3.

Improving Chronic Venous Disease Management with Micronised Purified Flavonoid Fraction: New Evidence from Clinical Trials to Real Life.

Chronic venous disease (CVD) develops in the microvessels, and is perpetuated by a vicious cycle of inflammation and endothelial activation, structural and functional changes to vessels and valves, and progressive venous hypertension. Data from animal models indicate that micronised purified flavonoid fraction (MPFF) has beneficial effects on a range of pathophysiological processes that contribute to CVD, including inflammation, micro-vessel permeability, valve and vessel wall remodelling, and reflux in microvalves. These effects explain its beneficial effects on the signs and symptoms of CVD, which have been seen across the spectrum of Clinical, Etiological, Anatomical and Pathophysiological (CEAP) categories of CVD severity. This includes patients with symptoms but no detectable anatomical or pathophysiological anomalies (C0s or C1) and patients with varicose veins (C2). In addition to symptomatic improvement, MPFF has been shown to reduce oedema in patients with C3 CVD, resolve skin symptoms in patients with C4 CVD, and accelerate the healing of venous ulcers in patients with C6 CVD. MPFF is highly recommended in international guidelines of CVD management and is the only veno-active drug to receive guideline endorsement for an improvement in patient quality of life.

Optimising Decision Making in Chronic Venous Disease Management with Micronised Purified Flavonoid Fraction.

Evidence-based medicine favours randomised controlled trials to limit bias and establish the effects of a treatment with statistical rigour. However, the controlled conditions and careful patient selection of randomised trials may produce results that cannot be generalised to a more diverse patient population in clinical practice. Therefore, there is growing recognition of the importance of supplementing randomised trial data with real-world evidence. Micronised purified flavonoid fraction has been investigated in several large-scale real-world studies, including the RELIEF and DECIDE studies, each of which included more than 1000 patients with chronic venous disease. These studies demonstrated a significant reduction in the prevalence and severity of chronic venous disease symptoms, and an improvement in quality of life. The chronic VEnous dIsorders maNagement and treatment effectivenesS evaluaTion in chronic vEnous disease, an international Program (VEINSTEP) study (NCT04574375), is currently underway in more than 6000 patients with chronic venous disease in nine countries. Preliminary data from one country (Morocco) indicate that chronic venous disease drug treatment, which was micronised purified flavonoid fraction in 75.7% of patients, was associated with a statistically significantly reduction in symptoms and improved quality of life. The overall results are awaited with interest. International chronic venous disease guidelines grade the evidence for micronised purified flavonoid fraction highly, as the benefits of micronised purified flavonoid fraction have been proven in randomised clinical trials and meta-analyses. Real-world studies demonstrate that the randomised evidence for micronised purified flavonoid fraction is generalisable to a clinical practice setting. Treatment decisions in chronic venous disease should consider evidence-based recommendations, including real-world data, as well as patient goals of symptom relief, functional improvement and/or better quality of life.

Pilot study on the effect of grape seed proanthocyanidin extract on inferior vene cava blood flow in patients with chronic venous insufficiency using 4D flow MRI.

BACKGROUND: Four-dimensional (4D) flow magnetic resonance imaging (MRI) was used to objectively assess changes in blood flow velocity in patients with chronic venous insufficiency (CVI) who underwent stocking treatment alone and stocking combined with Grape seed proanthocyanidin extract (GSPE) treatment. METHODS: Patients diagnosed with CVI were recruited from August 31, 2018 to December 31, 2020. A total of 23 participants were selected, with 10 and 13 patients in the stocking treatment and stocking + GSPE treatment groups, respectively. The blood flow velocity (Th-plane peak and average velocities) was calculated using 4D flow MRI. A paired t test was used to evaluate the differences in blood flow velocity before and after treatment. RESULTS: In the stocking treatment group, The Th-Plane peak velocity increased by 2.48 ±â€…5.05 cm/s after treatment (P = .16). In the stocking + GSPE treatment group, the Th-Plane peak velocity increased by 4.85 ±â€…5.57 cm/s after treatment (P < .001). CONCLUSION: The blood flow velocity on 4D flow MRI was significantly increased in participants who underwent GSPE, highlighting the potential of GSPE for CVI treatment.

Development of recommendations for the use of venoactive drugs in the treatment of chronic venous disease - where they are effective and where they are not.

The article provides an overview of the development of recommendations for indications of venoactive drugs for treating symptoms and signs associated with chronic venous disease (CVD). Venoactive drugs may be beneficial in patients with subjective problems and/or swelling of the lower limbs, after surgery for varicose veins, in chronic venous insufficiency or in microcirculatory disorders. They are not indicated in asymptomatic patients with CVD, in the prevention of varicose veins or to prevent their progression. Drugs with proven efficacy in clinical trials should be preferred.

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

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.

Ginkgo biloba, troxerutin and heptaminol chlorhydrate combined treatment for the management of venous insufficiency and hemorrhoidal crises.

OBJECTIVE: Ginkor Fort® (Tonipharm, Recordati Group; GB-T-H combined treatment) comprises ginkgo biloba extract, troxerutin and heptaminol chlorhydrate. It is a venotonic and vasculoprotective agent that strengthens veins, increases vessel resistance, and reduces permeability. Thanks to these synergistic actions, it is indicated for the treatment of signs and symptoms of venous insufficiency (VI) and signs related to the hemorrhoidal crisis. This review recapitulates the rationale for using venotonics to manage VI and discusses available evidence on the use of GB-T-H combined treatment to manage VI and hemorrhoidal crisis. MATERIALS AND METHODS: Papers were retrieved by a PubMed search using different keywords. No language or publication date restrictions were used. Documents from the Authors' literature collection were also considered. Papers were selected for inclusion according to their relevance to the topic. RESULTS: Preclinical and clinical studies showed that the GB-T-H combined treatment acts on both the acute phase symptoms and the pathogenetic mechanisms of the VI, through the prevention of the hypoxia-induced activation of endothelial cells, the reduction of the capillary tone and the hemostatic activity. This leads to the long-term slowing of the disease progression, suggesting that the GB-T-H combined treatment can manage the acute clinical manifestations and as a prevention measure with prolonged use in both VI and hemorrhoidal crises. In the available study, the GB-T-H combined treatment showed excellent tolerability. CONCLUSIONS: Available literature evidence and extensive clinical experience support the use of the GB-T-H combined treatment as an effective and safe option for treating and preventing the clinical manifestation of VI and hemorrhoidal crisis.

Micronized purified flavonoid fraction-based conservative treatment of chronic venous disease in a real-world setting.

Aims: To investigate the effectiveness and tolerability of adjunctive micronized purified flavonoid fraction (MPFF) in patients with chronic venous disease (CVD). Patients & methods: This observational study included adults (≥18 years) with clinical-etiology-anatomy-pathophysiology (CEAP) class C4 CVD for whom MPFF was indicated. Outcomes included changes in subcutaneous adipose thickness, venous clinical severity score, CVD symptoms (using a visual analogue scale) and tolerability. Results: Of 381 patients, 365 completed the study. After 6 months, subcutaneous adipose tissue thickness, venous clinical severity score and visual analogue scale scores significantly improved (all p < 0.001 vs baseline). No adverse drug reactions occurred. Conclusion: Adjunctive MPFF treatment improves skin and subcutaneous tissue conditions in CVD patients. Clinical Trial Registration: NCT04138576 (ClinicalTrials.gov).

Chronic venous disease (CVD) can cause a range of signs and symptoms that reduce patient quality of life. Micronized purified flavonoid fraction (MPFF) is a type of venoactive drug that is recommended in patients with early and advanced CVD. This study investigated the effectiveness and safety of MPFF when added to conservative treatment in patients with advanced CVD with long-term follow-up. After 6 months of MPFF, we observed significant improvements in the skin and subcutaneous tissue, symptoms and patient quality of life; no adverse drug reactions were reported. Therefore, MPFF-based conservative treatment can effectively and safely treat CVD.

Conservative therapy significantly reduces patients' chronic venous disease symptoms: A Caribbean insight into the VEIN Act Program.

OBJECTIVES: We sought to determine the baseline demographic and clinical characteristics of patients with Chronic Venous Disease (CVD) across the Caribbean, and to evaluate patients' compliance to conservative therapy and the effectiveness of such therapy in reducing patients' CVD symptoms. METHOD: Patients were enrolled into the VEIN Act Program, and their demographic data, CVD symptoms (and their intensity) and CEAP C-classification was recorded at the first visit. Patients were prescribed conservative therapy, and symptom intensity and patient compliance and satisfaction evaluated at a follow-up visit. RESULTS: We enrolled 193 patients into the study, most of which (76%) were female, between 39-78 years (80%) and within the C2-C4a classes (56.1%). Pain (61.1%) and heaviness (58.5%) were the most common symptoms. Patient compliance to the prescribed treatment was relatively high for all modalities (>75%) and most patients (92.1%) were at least somewhat satisfied with their treatment. CONCLUSIONS: Patient compliance to conservative therapy for management of CVD is high across the Caribbean, and such therapy is effective in reducing intensity of CVD symptoms.

Drugs containing extracts from Ruscus in chronic venal disease therapy - what's new we know about their effects?

Pharmacotherapy of venous insufficiency is based on the use of drugs which, through their mechanism of action, contribute to the complex pathomechanism of this disease. One of the drugs used in the treatment of CVD are extracts of Ruscus. Numerous studies have demonstrated a multidirectional mechanism of action involving the effect of the drug on the adrenergic and cholinergic systems and the intracellular calcium metabolism. All these mechanisms are responsible for the multidirectional mechanism of action of the drug.

Impact of statin treatment on patients diagnosed with chronic venous disease. Morphological analysis of the venous wall and clinical implications.

OBJECTIVES: The study evaluates the potential morphological changes that may occur in the venous wall in the case of the patients with chronic venous disease which associates treatment with statins for at least 2 years. METHODS: Operated patients with chronic venous disease in the CEAP C2-C3 stage were included in the study. 215 venous fragments, collected from 50 patients within the study group and 179 venous fragments collected from 52 patients within the control group were microscopically analysed, evaluating a series of morpho-anatomical parameters. RESULTS: In the study group, it was found that, venous reflux predominantly affects small veins, and also, a significant increase in collagen deposits in the adventitia and media tunics, proportional to the thickening of the venous wall. CONCLUSION: Our results indicate possible effects of statins upon the venous morphology. Further studies are needed to determine the impact of these results on daily practice.

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.

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).

Time course of microvalve pathophysiology in high pressure low flow model of venous insufficiency and the role of micronized purified flavonoid fraction.

BACKGROUND: The aim of this study was to characterize, in an experimental model, the mechanisms involved in the initiation of venous insufficiency at the level of microvenous valve and whether they can be influenced by early treatment with micronized purified flavonoid fraction (MPFF). METHODS: The external right iliac vein of 78 male golden Syrian hamsters was ligated to induce chronic venous insufficiency. Internal venular diameter as well as leukocyte-endothelium-interaction (leukocytes sticking after staining with rhodamine 6G), were assessed using an intravital microscope. In the second part of the study 30 animals were divided into three groups and underwent: ligation plus MPFF, ligation plus 10% lactose solution (vehicle), or sham operation. Treatment with MPFF 100 mg/kg/day or vehicle started 2 days before ligation and lasted for 7 days. Venular diameter and number of adherent leukocytes were assessed 5 days post-ligature. RESULTS: Venular diameter increased immediately after ligature and reached a maximum at 4 hours (P<0.001 vs. baseline), followed by a plateau before gradually returning to baseline dimensions. The increase in the number of adherent leukocytes was also immediate but attained maximal number at 3 days (P<0.0001), followed by a plateau and then gradual return to baseline numbers. In MPFF-treated animals, leukocyte adhesion to the microvalves was prevented compared with vehicle-treated animals (P<0.0001) and venular diameter was also significantly reduced (P<0.05). CONCLUSIONS: Venous hypertension induced immediate venular dilatation followed by an increase in the number of adherent leukocytes at microvalve level. Treatment with MPFF prevented the initiation of microvalve inflammation and may play a protective role in the progression of chronic venous insufficiency.