Venoactive Drug Research Articles

The Effects of Different Dosages on Micronized Purified Flavonoid Fraction's Treatment of Lower Limb Chronic Venous Disease: A Meta-Analysis.

Micronized purified flavonoid fraction (MPFF) is a widely prescribed and extensively investigated venoactive drug (VAD). The standard dosage for MPFF is 500 mg administered twice daily. However, a new daily dose of 1000 mg has just been introduced. This study investigated whether a daily dose of 1000 mg MPFF could be implemented and embraced by the public and still has the same therapeutic effects as conventional pharmaceuticals. For this meta-analysis, we searched MEDLINE, Embase, Science of Web, Cochrane, and PubMed databases and forward and backward citations for studies published between database inception and March 2023. Three randomized controlled trials (RCTs) of comparison of different dosages of MPFF to evaluate whether there is a significant difference between them were included, without language or date restrictions. Due to the small sample size of the study included, we conducted a simple sensitivity test using a one-by-one exclusion method, and the results showed that the study did not affect the final consolidation conclusion. The quality of the evidence was assessed using the Cochrane risk-of-bias tool. Out of 232 studies, 99 were eligible and 39 RCTs had data, all with low to moderate bias. Overall, 1924 patients (experimental group: 967, control group: 957) in 3 RCTs met the criteria. There is no significant difference in patient compliance, efficacy, clinical adverse events, and quality of life scores between MPFF 1000 mg once daily and MPFF 500 mg twice daily (standardized mean difference [SMD]: 0.049 [0.048, 0.145], p=0.321, risk ratio [RR]: 0.981 [0.855, 1.125], p=0.904, and SMD: 0.063 [0.034, 0.160], p=0.203). In symptomatic chronic venous disease patients, MPFF 1000 mg once daily and MPFF 500 mg twice daily improve patient compliance, lower limb discomfort, clinical adverse events, and quality of life scores similarly. Regular medical care should recommend MPFF 1000 mg daily more often. Micronized purified flavonoid fraction (MPFF) is a popular venoactive medication (VAD) in modern medicine.MPFF is effective in treating lower extremity venous problems.Currently, besides conventional 500 mg tablets, there exist alternative dosage forms such as solutions, chewable tablets, and other novel formulations for MPFF.The excessive frequency and amount of medication may have a negative impact on patient adherence.

Effect of Micronized Purified Flavonoid Fraction on Venous Hemodynamics Evaluated Using Digital Photoplethysmography in Patients with Chronic Venous Disease

Micronized purified flavonoid fraction (MPFF) is the most widely prescribed and well-studied venoactive drug available for the treatment of chronic venous disease (CVD). Photoplethysmography (PPG) is used to quantitatively measure venous hemodynamics and provide information about the overall function of the venous system. The aim of this study was to use digital PPG to evaluate the effects of MPFF on venous hemodynamics in patients with CVD. Patients diagnosed with CVD at an outpatient clinic in Bursa, Turkey between February 2018 and July 2020 were assessed for inclusion in this retrospective analysis. Patients who complied with the advised treatment strategy (MPFF 1,000mg tablets taken orally once daily and compression garments) and attended follow-up visits were included in the analysis. Digital PPG was used to measure venous refilling time (VRT) and venous pumping capacity (VPC) at diagnosis and 6months of follow-up. The Venous Clinical Severity Score (VCSS) was also obtained at these visits, and patients completed the 20-item Chronic Venous Insufficiency Questionnaire (CIVIQ-20). In total, 721 patients (mean age 52years) with C0-C4 CVD were included in the study. PPG showed that VRT and VPC increased significantly from 19.0sec to 2.0%, respectively, at diagnosis to 27.4 and 4.9%, respectively, at 6months (both P<0.05). Mean VCSS improved significantly from 7.9 at diagnosis to 3.1 at 6months (P<0.05). Mean CIVIQ-20 score also improved significantly at the 6-month follow-up (20.1 vs 38.6 at diagnosis; P<0.01). In patients with C0-C4 CVD, 6months of MPFF treatment plus the wearing of compression garments was associated with statistically significant improvements in venous hemodynamic parameters measured by PPG, as well as measures of clinical severity and quality of life.

Effects of Venoactive Drug Therapy and Ovarian Vein Interventions on Vasoactive Neuropeptide and Cytokine Levels in Patients with Pelvic Venous Disorders

To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVDs). The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound of the pelvic veins, the patients were allocated to the VAD therapy (n=38) or OVE/OVR (n=32). Additionally, the enzyme-linked immunosorbent assay tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3months after OVE/OVR. The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8, and MCP-1 levels were detected after treatment. At 3months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in ovarian veins, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7±0.1ng/mL and 0.12±0.02ng/mL before treatment; 0.5±0.12ng/mL and 0.09±0.06ng/mL after treatment, respectively; all P<0.05). No changes in cytokine levels were revealed. Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels.

Clinical efficacy of sodium aescinate administration following endovenous laser ablation for varicose veins.

Endovenous interventions and minimally invasive procedures are effective in the management of varicose veins. However, they can cause postoperative discomfort. To evaluate the clinical efficacy of sodium aescinate (SA) in improving edema, pain, vein-specific symptoms, and quality of life in patients following endovenous laser ablation (EVLA) for varicose veins. In this single-center randomized controlled trial (RCT), patients were allocated into two groups: in Group A, 60mg SA was administered twice daily for 20days, and in Group B (control), no venoactive drug was prescribed. The Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system for chronic venous disorders was used to assess the varicose veins. The circumferences of the calf and ankle were recorded for evaluating edema. The 10-point Visual Analog Scale (VAS), Venous Clinical Severity Score (VCSS), and Aberdeen Varicose Veins Questionnaire (AVVQ) were used to measure the pain intensity, overall varicose vein severity, and patient's quality of life, respectively. The study included 87 patients (mean age, 59.9 ± 10.7years; 54 men) with CEAP class C2-C5 varicose veins who underwent EVLA and phlebectomy or foam sclerotherapy. The calf circumference recovered quicker in Group A than in Group B by days 10, 21, and 30 (difference from baseline was 1.04 ± 0.35 vs 2.39 ± 1.15 [p < .001], 0.48 ± 0.42 vs1.73 ± 1.00 [p < .001], and 0.18 ± 0.64 vs 0.82 ± 0.96 [p < .001], respectively). The ankle circumference recovered quicker in Group A than in Group B by days 10 and 21 (the difference from baseline was 1.37 ± 0.52 vs 2.36 ± 0.93 [p < .001] and 0.58 ± 0.60 vs 1.14 ± 0.88 [p = .002], respectively). Pain relief was achieved quicker in Group A than in Group B (0.257 ± 1.097 [p = .0863] vs 0.506 ± 1.250 [p = .0168] by day 21). There were no significant differences in the VCSS and AVVQ scores between both groups. There were no drug-related adverse effects. SA, in combination with compression therapy, can relieve edema and alleviate pain in patients following EVLA for varicose veins.

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

IntroductionChronic 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), Raktavaritavāta (disorders of vāta occluded by rakta ∼ blood), ApanaVaigunya (vitiated apānavāyu), 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. MethodsThis 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. ResultsThe 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. ConclusionThe 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.

Conocimiento de la enfermedad venosa crónica en los profesionales sanitarios en España

IntroductionChronic venous disease (CVD) is classified as the most prevalent vascular disease in humans. It has been associated with an increased incidence of cardiovascular diseases and is a strong predictor of all-cause mortality, representing a public health problem of the first magnitude. The objective of this study was to analyze the actions in the management of CVD in the daily clinical practice of health professionals in Spain. Material and methodsObservational, descriptive and cross-sectional study with data collection through an opinion survey of 22 questions completed electronically through a Google® form for professionals involved in chronic venous disease care. Three hundred surveys were analyzed. The quantitative variables were represented with means and standard deviation and the qualitative ones with percentages and confidence intervals. ResultsThree hundred surveys analyzed. 65.3% were women. The most participatory age group was over 55 years of age. 85% of those surveyed considered that CVD is an underdiagnosed and undertreated disease, with an added negative impact in terms of follow-up during the Covid-19 pandemic, since 91.7% considered that it had not been adequate. 47% of the participants did not know the CEAP classification and 56.3% did not know the venous clinical severity scale (VCSS). 92.7% of physicians prescribed compression stockings and 74.7% phlebotonic drugs. Hidrosmine was the best known and most prescribed venoactive drug (51.7%). 73% of the doctors recognized that they did not use any algorithm or protocol for the diagnosis, treatment and monitoring of CVD in their usual clinical practice and 91% stated that they were not trained in their workplaces. 54.3% of the physicians believed that one of the main limitations that made follow-up of the disease difficult was the lack of coordination with the vascular surgeons. ConclusionsUpdating and responding to the training needs of professionals regarding CVD is essential to guarantee quality care continuity in the care of our patients.

Novel holistic pharmacokinetic model applied to plasma and urine concentrations of 2,5-dihydroxybenzene sulphonate following administrations of calcium dobesilate and etamsylate to exercised horses.

Calcium dobesilate (CD) is a synthetic venoactive drug used in veterinary medicine to treat equine navicular disease. Etamsylate is a haemostatic agent used in horses for the treatment of exercise-induced pulmonary haemorrhage. Both etamsylate and CD dissociate in the circulatory system with 2,5-HBSA as the active drug. The aim of the research was to be able to provide detection time (DT) advice from pharmacokinetic (PK) studies in Thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Two (pilot study) and six (final study) horses were given 28 and 9 repeated dose of CD (3 mg/kg BID) respectively. Two horses were each given a single intravenous (IV) dose of etamsylate (10 mg/kg). Plasma and urine 2,5-HBSA concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CD pilot study revealed that steady state could be reached with a few days and that 2,5-HBSA in plasma and urine shows instability during storage at -20°C but appears stable at -80°C. A novel holistic non-linear mixed-effects three-compartmental PK model was developed that described both plasma and urine concentrations of 2,5-HBSA, from either CD or etamsylate administration. Typical values for 2,5-HBSA clearance and bioavailability were 2.0 mL/min/kg and 28% respectively. Using the parameters obtained from this PK model, in conjunction with methodology developed by Toutain, afforded a possible screening limit (SL) that can regulate for a DT of 3 days in urine; however, a corresponding SL in plasma would be below current levels of detection. However, it is the responsibility of the individual racing authorities to apply their own risk management with regard to SLs and DTs.

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.

A nationwide study of compliance of venoactive drugs in chronic venous disease patients.

Venoactive drugs are widely used to improve the symptoms and signs of chronic venous disease. This study aimed to analyze the rate of adverse events after venoactive drug prescription and subsequent compliance and switching rates. Using the National Health Insurance Service database, individuals with at least one chronic venous disease code between January 2009 and December 2019 were identified, and 30% (2,216,780 individuals) of these were sampled. Finally, 1,551,212 patients were included, and we analyzed adverse events, compliance, and switching rates with 8 venoactive drugs, including Vitis vinifera extract, naftazone, micronized purified flavonoid fraction, Vitis vinifera leaf extract, diosmin, diobsilate calcium, bilberry fruit dried extract, and sulodexide. The most commonly prescribed venoactive drug was Vitis vinifera extract (72.2%), followed by sulodexide (9.3%), and Vitis vinifera leaf dry extract (8.2%). Adverse event rates were significantly lower in the naftazone and diosmin groups (P = 0.001 and P = 0.002, respectively) and significantly higher in the Vitis vinifera leaf dry extract group (P = 0.009). Drug adherence to sulodexide was the highest throughout the study period, followed by billberry extract and dobesilate (all P < 0.001). For most drugs, the drug switching rate was low (<5.0%). Vitis vinifera extract was the most commonly prescribed venoactive drug in Korea, and drug adherence to sulodexide was the highest among all venoactive drugs. The adverse event rates were significantly lower in the naftazone and diosmin groups.

Venoactive Drug Treatment or Compression Stockings in Warm Weather Season in Symptomatic Patients with Chronic Venous Disease

Venoactive Drug Treatment or Compression Stockings in Warm Weather Season in Symptomatic Patients with Chronic Venous Disease

Monocyte chemoattractant protein 1 plasma concentration in blood from varicose veins decreases under venoactive drug treatment.

Vein-specific inflammation leads to vascular smooth muscle cells proliferation and extracellular matrix degradation of vein wall. This process is known as remodeling and is promoted by "trapped" leukocytes. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for trafficking of leukocytes from blood to vein wall. The aim of this study was to measure the MCP-1 concentration in varicose veins blood before and after venoactive drug therapy and to compare it with a concentration of blood from varicose veins of subjects who did not receive drug treatment. Non-randomized comparative study was conducted on 30 patients with primary varicose veins. 20 patients of the study group received diosmin 900 mg/hesperidin 100 mg once daily. 10 controls received no treatment. MCP-1 level was measured (pg/mL) in the blood from varicose veins twice, at the day of inclusion and after 60 days. Legs discomfort related to chronic venous disease (CVD) symptoms was measured with 10-cm Visual Analogue Scale (VAS) at inclusion and at completion of the study. Median (interquartile range, IQR) MCP-1 concentrations in treatment and control groups at inclusion were 171.9 (124.4-216.0) and 157.0 (120.1-163.1), resp., P=0.285. After 60 days of treatment MCP-1 level decreased, but non-significantly to 152.3 (124.1-178.3). In patients who did not receive treatment chemokine level slightly increased to 163.0 (134.0-172.9). Median changes over time were -6.6 (-30.9-7.4) and 10.6 (-3.7-19.2) in the study and control groups, resp. (P=0.048). After 60 days in 12 of 19 and 2 of 9 patients of treatments and control groups MCP-1 decreased (P=0.103). Odds ratio for MCP-1 decreasing was 9.5 (95% CI 1.1-81.5, P=0.043) for those who received venoactive drug. Mean (± standard deviation [SD]) legs discomfort significantly dropped in the study group from 5.7 (±2.5) to 1.9 (±2.2) (P=0.0003), while in controls no changes were registered: 3.4 (±1.3) and 3.5 (± 1.4), resp., P=0.28). Mean difference of VAS at baseline and at follow-up was -3.5 (±2.6) and 0.9 (±2.1), resp. (P<0.0001). Plasma concentration of MCP-1 in varicose veins blood demonstrates a tendency to decrease under two months treatment with a venoactive drug. Future studies are needed to reveal a possible role of MCP-1 as a target considering its role in varicose veins pathogenesis.

Modulatory Effect of Diosmin and Diosmetin on Metalloproteinase Activity and Inflammatory Mediators in Human Skin Fibroblasts Treated with Lipopolysaccharide.

Diosmin is widely used as a venoactive drug in the pharmacological treatment of chronic venous disorders. It exerts a strong protective effect on blood vessels via an increase in the elasticity of vessel walls and reduces the permeability of capillary walls, thereby producing an anti-edematous effect. In this paper, we investigated the effectiveness of diosmin and diosmetin in modulating the level of proinflammatory factors in human skin fibroblasts treated with lipopolysaccharide (LPS). Two variants of the experiments were performed: the flavonoid was added 2 h prior to or 24 h after LPS stimulation. Our study revealed that both flavonoids reduced the levels of IL-6 and Il-1β as well as COX-2 and PGE2 but had no impact on IL-10. However, the addition of the compounds prior to the LPS addition was more effective. Moreover, diosmetin modulated the proinflammatory factors more strongly than diosmin. Our investigations also showed that both flavonoids were potent inhibitors of elastase and collagenase activity, and no differences between the glycoside and aglycone forms were observed.

Lymphotonic activity of Ruscus extract, hesperidin methyl chalcone and vitamin C in human lymphatic smooth muscle cells

Besides actions including their venotonic, anti-inflammatory, and anti-oxidant effects, venoactive drugs are expected to act on edema via their action on lymphatics. The objective of this study was to evaluate the effect of the combination of Ruscus, hesperidin methyl chalcone and Vitamin C (Ruscus/HMC/Vit C) on intracellular calcium mobilization and contraction of human lymphatic smooth muscle cells (LSMCs) to better characterize the mechanism of its lymphotonic activity. Calcium mobilization was evidenced by videomicroscopy analysis of the fluorescence emitted by a specific Ca2+ sensitive dye and measured after injection of Ruscus/HMC/Vit C at 0.1, 0.3, 1.0, and 3.0mg/mL into LSMCs. Ruscus/HMC/Vit C induced a strong and reproducible concentration-dependent calcium mobilization in LSMCs. On the contrary, another venoactive drug used as comparator, micronized purified flavonoid fraction (MPFF), did not induce calcium mobilization whatever the tested concentration. Although alternative mechanisms of action may result in potential lymphotonic effects, the efficacy of lymphotonic products is nonetheless related to their stimulating effect on the contractile activity of the smooth muscle cells surrounding lymphatic vessels. In the light of the results obtained in this study, the direct effect of Ruscus/HMC/Vit C on LSMC contraction may partially explain its clinical efficacy on lymphotonic activity, as has been observed in terms of objective signs of edema as reported in the recent guidelines on chronic venous disease.

Effectiveness of Vascular Balneotherapy in the Treatment of Chronic Venous Disease (CVD)

Aim: Inside the “Antica Querciolaia” Thermal Station, located in the municipality of Rapolano Terme (Siena), there is a well, called “Well 5 – Cold Bath”, from which gushes a homeothermic alkaline bicarbonate-sulphate mineral water, considered suitable for thermal use with venous vascular address. The main endpoint of the study was to demonstrate the effects of vascular balneotherapy with thermal mineral water on classical symptoms, such as edema and quality of life of patients with chronic venous disease in the lower limbs, while the secondary endpoint was to verify the efficacy and tolerability of vascular balneotherapy carried out in predefined vascular paths and with a standardized protocol. Materials and Methods: In the double-blind, randomized controlled study, 60 patients with chronic venous disease of the lower limbs were enrolled in the first three stages of the CEAP classification. The patients were divided into two equivalent groups: “Balneotherapy Group”, treated with baths in thermal mineral water from “Well 5 – Cold Bath” and venoactive drug therapy and “Control Group” which only took drug therapy in an equivalent dose and duration. Results: The results of the study show a clear improvement of the “Balneotherapy Group” compared to the “Control Group” in the treatment of chronic venous disease of the lower limbs, concerning both the primary and secondary endpoints set by the study. Conclusions: Our findings show the undoubted efficacy and excellent tolerability of vascular balneotherapy in the treatment of chronic venous disease of the lower limbs.

The Effect of Venoactive Drug Therapy on the Development and Severity of Post-Embolization Syndrome in Endovascular Interventions on the Gonadal Veins.

Objective. To evaluate the incidence of post-embolization syndrome (PES) and the effect of venoactive therapy on its development, severity, and duration after endovascular embolization of gonadal veins (EEGV) with coils in patients with pelvic congestion syndrome (PCS). Materials and Methods. We analyzed the outcomes of EEGV with coils in 70 female patients who received (n = 38; group 1) or did not receive (n = 32; group 2) treatment with a venoactive drug (VAD) before and after the procedure. Assessments of the EEGV efficacy and for possible signs of PES were done on days 1, 5, 10, 15, 20, and 30 after the intervention. All patients underwent transvaginal and transabdominal duplex ultrasound scanning (DUS) after EEGV. In addition, patients with PES were examined using the computed tomography of the pelvic veins in the postprocedural period. Results. Technical success of EEGV was achieved in 100% of patients. Pelvic venous pain (PVP) reduction after EEGV was observed in 77.1% of patients. The PES was diagnosed in 18.6% of cases (10.5% in group 1 vs. 28.1% in group 2, p > 0.05). In three patients of group 1, the protrusion of coils was suspected and eventually verified during the resection of the left gonadal vein with coils. The group 1 patients had less severe post-embolization pain (6.2 ± 0.4 vs. 7.8 ± 0.3 scores in group 2; p = 0.009) and three times shorter duration of PES (5.0 ± 1.2 vs. 16.2 ± 2.7 days; p = 0.003). No significant differences in the diameters of gonadal veins, side of embolization, and number of coils were revealed between patients with and without PES. The rate of parametrium vein thrombosis was found to be significantly higher in patients with PES than in those without PES (30.7% vs. 18.5%, respectively; p < 0.05). Conclusion. The PES is a frequent complication of EEGV with coils and occurs in 18.6% of patients. Venoactive treatment does not effect the incidence of this complication but reduces the PES severity and duration.

Efficacy of Micronized Purified Flavonoid Fraction-Based Venoactive Therapy After Endovenous Mechanochemical Obliteration: Prospective Comparative Study

BackgroundEndovenous interventions and minimally invasive open procedures are effective in the management of varicose veins, but can result in post-operative pain/discomfort.ObjectiveThe objective of this study was to evaluate the clinical efficacy of micronized purified flavonoid fraction venoactive therapy for postoperative pain, vein-specific symptoms, and quality of life in patients with varicose veins following an endovenous mechanochemical ablation procedure.MethodsThis prospective, observational, single-center study allocated patients into two groups: Group A, micronized purified flavonoid fraction 1000 mg once daily for 30 days; Group B, no venoactive drug prescribed (control). The Clinical-Etiology-Anatomy-Pathophysiology classification system for chronic venous disorders was used to assess varicose veins; a 10-point Visual Analog Scale assessed pain syndrome intensity; the Venous Clinical Severity Score measured overall varicose vein severity; and the Chronic Venous Insufficiency QoL Questionnaire measured total quality of life.ResultsThe study enrolled 58 patients (mean age 36.9 ± 4.1 years; 24 men) with varicose veins of C2–C4 who underwent truncal mechanochemical ablation plus mini-phlebectomy or foam sclerotherapy. Group A had significantly lower pain syndrome at days 14 and 30 compared with Group B (1.76 vs 2.20, p = 0.039; 1.38 vs 2.07, p = 0.003, respectively), and clinical symptom severity at day 30 (2.67 vs 3.13, p = 0.05). Significant differences in quality-of-life scores existed between groups at days 14 and 30 (15.21 vs 18.75, p = 0.008; 12.98 vs 16.33, p = 0.001). No micronized, purified flavonoid, fraction-related adverse effects were observed.ConclusionsMicronized purified flavonoid fraction-based venoactive adjuvant therapy after mechanochemical ablation alleviated pain, reduced the severity of symptoms, and improved the quality of life in patients with varicose veins.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-021-00249-4.

Efficacy of two micronized purified flavonoid fraction dosing regimens in the pelvic venous pain relief.

The venoactive drug treatment regimen for pelvic venous disorders (PeVDs) is not finally established. The study aimed at assessing the efficacy of micronized purified flavonoid fraction (MPFF) in a standard or double dose in the pelvic venous pain (PVP) relief in PeVD. We analyzed the treatment efficacy in 125 female patients with PeVD, who were allocated to two groups with MPFF treatment in a regular dose of 1000 mg once daily (OD) for 2 months (N.=65; group 1) or double dose of 1000 mg twice daily for 1 month and then 1000 mg OD for 1 month (N.=60; group 2). Patients underwent clinical examination along with an assessment of the PVP severity using the visual analogue scale (VAS) ranged from 0 to 10 scores, transvaginal and transabdominal duplex ultrasound scanning (DUS), and single-photon emission computed tomography (SPECT) of the pelvic veins with in vivo-labelled red blood cells (RBCs). The groups were different at baseline in the PVP severity (3.4±1.2 vs. 7.3±0.5 scores in groups 1 and 2, accordingly; P=0.012). DUS and SPECT were used to evaluate diameters of gonadal, parametrial, and uterine veins, to assess the presence of reflux in them, to measure blood flow velocity in the internal iliac veins (V<inf>lin IIV</inf>), and to calculate the coefficient of pelvic venous congestion (C<inf>PVC</inf>). The treatment was associated with a significant reduction in the PVP score from 3.4±1.2 to 1.2±0.2 (P=0.03) when using the standard dose for 2 months and from 7.3±0.5 to 0.8±0.1 (P=0.001) when using the double dose in the 1st month. The PVP relief was achieved on average after 13.7±0.6 and 3.1±0.8 days in groups 1 and 2, accordingly (P=0.0001 between the groups). At month 2, the C<inf>PVC</inf> reduction was found to be significantly greater in group 2 compared to group 1 (46.6% vs. 25%; P=0.018). Side effects (gastralgia, flatulence) were reported by only 2 (3.3%) patients of group 2. The venoactive drug therapy with MPFF is an effective and safe option for the PVP relief in female patients with PeVD. The use of double dose in the 1st month seems to be appropriate in patients with greater PVP severity but is associated with an increased rate of side effects.

Postembolization syndrome in endovascular interventions on the gonadal veins

ObjectiveThe present study evaluated the incidence of postembolization syndrome (PES) after endovascular coil embolization of the gonadal veins (EEGV) in patients with pelvic congestion syndrome and investigated the appropriate medical treatment. MethodsEEGV was performed in 70 female patients with pelvic congestion syndrome (left-sided in 58, right-sided in 3, and bilateral in 9 patients). For embolization, 0.035-in. coils with an 8- to 12-mm diameter and 10- to 20-cm length were used. Assessments of the EEGV results and possible PES symptoms were performed on days 1, 5, 10, 20, and 30 after the procedure and included transvaginal and transabdominal duplex ultrasound scanning of the pelvic veins and at the embolization site. ResultsPES had manifested with increased pelvic pain, tenderness along the embolized vein, and hyperthermia ≤37.5°C to 37.8°C and had developed in 14 patients (20%). For PES treatment, a nonsteroidal anti-inflammatory drug (diclofenac, 75 mg daily for 3-7 days; mean, 4.2 ± 1.1 days) and a venoactive drug (micronized purified flavonoid fraction, 1000 mg daily for 2 months) were used. Medical treatment was associated with a significant reduction in PES symptoms in all patients within 14 days and complete resolution by day 30 after embolization. duplex ultrasound scanning revealed thrombosis of parametrial veins in 12 of 56 patients (21.4%) with successful EEGV and 3 of 14 patients (21.4%) with PES. ConclusionsIn patients who have undergone EEGV, increased pelvic pain, the occurrence of tenderness along the embolized vein, and the presence of hyperthermia should be considered as PES manifestations. In our study, PES occurred in 20% of the treated patients.

Reducing hyperpigmentation after sclerotherapy: A randomized clinical trial

ObjectiveSclerotherapy for the treatment of varicose veins is one of the most common medical procedures performed in the Western world, and hyperpigmentation is one of the most frequent, dreaded, minor adverse events. There has recently been some interest in investigating the inflammatory response of the local endothelium after sclerotherapy and the possible benefits of venoactive drugs because of their pleiotropic properties. The aim of this study was to evaluate whether adding a venoactive drug (sulodexide) to the standard sclerotherapy treatment protocol for patients with varicose veins can reduce the occurrence of postsclerotherapy hyperpigmentation. MethodsWe carried out a prospective, multicenter, randomized controlled trial with a parallel group design. It included 720 patients with telangiectasia, reticular veins, or varicose veins who were candidates for sclerotherapy. Patients with reflux in deep system or saphenous veins were excluded. Group A consisted of 354 patients who received an oral dose of sulodexide twice a day for 7 days before scheduled sclerotherapy; the treatment then continued for 3 months. Group B consisted of 366 patients who received the standard sclerotherapy protocol. Polidocanol was used as the sclerosing agent, and 20 to 30 mm Hg compression stockings were used in both groups for 7 days. Control photographs were taken, and a follow-up examination took place after 1 month and 3 months. Computer software was used to analyze the treated area for incidence of hyperpigmentation, total area of hyperpigmentation, skin tone increase in the hyperpigmented area, vein disappearance, and incidence of major bleeding. The sample size was calculated to give a statistical power of 80%. Student t-test and the χ2 test were used for comparative analyses, as appropriate. The level of significance was set at P < .05. ResultsA total of 609 patients completed the 3-month follow-up: 312 in group A and 297 in group B. After 1 month, the incidence of hyperpigmentation was 8.7% in group A and 14.8% in group B (P = .01). Group A developed an average area of hyperpigmentation of 10.7% compared with 18.2% in group B (P = .01), and the skin tone of the hyperpigmented area was lower in group A than in group B (P = .02). However, the latter difference was not significant after 3 months. The overall vein disappearance rate was similar in both groups. ConclusionsOur analysis shows that by adding a venoactive drug (sulodexide) to the standard sclerotherapy protocol, the occurrence of hyperpigmentation is reduced without affecting the desired therapeutic vein elimination response.

Reducing Hyperpigmentation After Sclerotherapy: Results of a Prospective, Multicenter, Randomized Trial

This study evaluated patients with varicose veins treated with sclerotherapy to determine whether adding a venoactive drug (sulodexide) to the standard treatment protocol can reduce the presence of postsclerotherapy hyperpigmentation.