cardiovascular-agents and Venous-Insufficiency

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

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Chronic Disease; Cost-Benefit Analysis; Diosmin; Disease Progression; Flavonoids; Humans; Life Style; Male; Quality of Life; Sclerotherapy; Vascular Diseases; Venous Insufficiency

Venous disease is common in Latin America, with an estimated 68.11% prevalence of chronic venous disease. The diverse social, political, and economic characteristics of the many nations that make up Latin America mean that different conditions affect how these diseases are diagnosed and treated, which may differ markedly from the way they are treated by the health care systems of the United States and Europe. Our goal was to review the current state of treatment of chronic venous insufficiency (CVI) in Latin America.. This is a narrative review of the medical literature on the subject and synthesizes sometimes fragmentary information on CVI across a large and diverse region.. CVI represents an unmet medical need in Latin America. Conservative treatments, such as compression stockings, may be used at first, and there are nonpharmacologic and complementary and alternative medicine approaches in use. Endovenous approaches, such as endovenous thermal ablation, have largely replaced surgical interventions. In Europe and the United States, such procedures are mainly carried out in ambulatory facilities, whereas they are mainly performed in the hospital in Latin America.. Recent strong economic growth in Latin America and improvements in social security and health care suggest that innovative approaches to chronic venous disease and CVI will be implemented.

Topics: Ablation Techniques; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Endovascular Procedures; Female; Humans; Latin America; Male; Sclerotherapy; Stockings, Compression; Treatment Outcome; Varicose Ulcer; Venous Insufficiency

Chronic venous disease (CVeD) is a highly prevalent condition in the general population, and it has a significant impact on quality of life. While it is usually manifested by obvious signs, such as varicose veins and venous ulcers, other symptoms of the disease are less specific. Among the other symptoms, which include heaviness, swelling, muscle cramps and restless legs, pain is the symptom that most frequently compels CVeD patients to seek medical aid. However, there is a substantial discrepancy between pain severity and clinically detectable signs of CVeD, questioned by several opposing studies. Further evaluation is needed to clarify this subject, and to analyse whether pain development predicts objective CVeD progression. General management of CVeD starts with advising lifestyle changes, such as lowering body mass index and treating comorbidities. However, the mainstay of treatment is compression therapy, with the additional use of pharmacological substances. Venoactive drugs proved to be the drugs of choice for symptom alleviation and slowing the progression of CVeD, with micronized purified flavonoid fraction being the most effective one. Interventional therapy is reserved for advanced stages of the disease.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Endovascular Procedures; Humans; Pain; Risk Assessment; Risk Factors; Risk Reduction Behavior; Stockings, Compression; Treatment Outcome; Varicose Veins; Venous Insufficiency

Chronic venous disease (CVD) is both prevalent and unavoidable in many people as a result of persistent or unalterable risk factors, the most important of which are advanced age, excess body weight, and family history. Given this inevitability, medical treatment is required to alleviate symptoms and slow disease progression. Venoactive drug therapy is emerging as a valuable treatment option for many CVD patients and micronized purified flavonoid fraction (MPFF) is the most widely prescribed and well-studied venoactive drug available. Recent evidence from animal models of venous hypertension and from clinical trials, as well as from systematic reviews, shows that MPFF is effective at alleviating many of the most common symptoms of CVD including leg pain, leg heaviness, sensations of swelling, cramps, and functional discomfort. In addition, MPFF improves the clinical signs of redness, skin changes, and edema, and improves quality of life. Collectively, these findings support the strong recommendation for MPFF treatment found in the 2018 international guidelines for the management of CVD.Funding: Servier.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Diosmin; Humans; Male; Pain; Risk Factors; Varicose Veins; Venous Insufficiency

The use of a venoactive drug is considered an important component of medical treatment of chronic venous disease (CVD), although the efficacy of certain venoactive drugs (VADs) on one or more individual leg symptoms or signs may have not been extensively studied to justify a strong recommendation in guidelines on CVD. The aim of this systematic review and meta-analysis was to study the effectiveness of the micronized purified flavonoid fraction (MPFF, Daflon®) across the spectrum of defined venous symptoms, signs, quality of life (QoL) and treatment assessment by the physician.. On September 9, 2017, a systematic review of the databases MEDLINE, Scopus and Cochrane Central was performed, supplemented by hand searching, to identify randomized double-blind placebo-controlled trials on MPFF in patients with CVD.. The main outcome measures were the individual and global symptoms, leg edema and redness, skin changes, QoL and evaluation of the overall effectiveness of the treatment by the physician. The effectiveness of MPFF compared with placebo was expressed as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Trial quality of evidence was graded using the GRADE system.. We identified 7 trials, mostly with low risk of bias, involving 1,692 patients. On qualitative analysis, MPFF significantly improved nine defined leg symptoms, including pain, heaviness, feeling of swelling, cramps, paresthesia, burning sensation, and pruritus (itching), but also functional discomfort compared with placebo, leg redness, skin changes and QoL. On quantitative analysis, MPFF compared with placebo, assessed as a categorical variable, reduced leg pain (RR 0.53, P=0.0001, NNT=4.2), heaviness (RR 0.35, P<0.00001, NNT=2.0), feeling of swelling (RR 0.39, P<0.00001, NNT=3.1), cramps (RR 0.51, P=0.02, NNT=4.8), paresthesia (RR 0.45, P=0.03, NNT=3.5), and functional discomfort (RR 0.41, P=0.0004, NNT=3.0). Similarly, MPFF compared with placebo, assessed as a continuous variable reduced pain (SMD -0.25, 95% CI -0.38 to -0.11), heaviness (SMD -0.80, 95% CI -1.05 to -0.54), feeling of swelling (SMD -0.99, 95% CI -1.25 to -0.73), burning sensation (SMD -0.46, 95% CI -0.78 to -0.14), cramps (SMD -0.46, 95% CI -0.78 to -0.14), and functional discomfort (SMD -0.87, 95% CI -1.13 to -0.61). Regarding objective assessments of leg edema, the use of MPFF compared with placebo reduced ankle circumference (SMD -0.59, 95% CI -1.15 to -0.02), and leg redness (SMD -0.32, 95% CI -0.56 to -0.07, RR 0.50, P=0.03, NNT=3.6), improved skin changes (RR 0.18, P=0.0003, NNT=1.6) and quality of life (SMD -0.21, 95% CI -0.37 to -0.04) and was associated with clinical improvement as assessed by the physician (RR 0.28, P<0.00001, NNT=2.5). Heterogeneity was mostly minimal. The existing evidence where sufficient was mostly of high quality.. Based on high quality evidence, MPFF is highly effective in improving leg symptoms, edema and quality of life in patients with CVD.

Topics: Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Diosmin; Double-Blind Method; Edema; Humans; Odds Ratio; Quality of Life; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Treatment Outcome; Varicose Veins; Venous Insufficiency

Despite a high level of the development of modern angiology and vascular surgery, the problem of chronic venous insufficiency (CVI) complicating the course of various venous diseases seems to have no tendency towards being solved, thus calling forth permanent search for optimization of methods of treatment and rehabilitation of patients presenting with the above-mentioned syndrome. The article presents a review of contemporary studies dedicated to the problem of correcting CVI. Special attention is paid to the endothelial state in CVI and possibilities of correcting endothelial dysfunction with the use of bioflavonoids, in particular, diosmin. Also presented herein are the results of an original experimental study dedicated to peculiarities of the endothelial functional state, endothelial dysfunction, and correction thereof on the background of the existing CVI.. Несмотря на высокий уровень развития современной ангиологии и сосудистой хирургии, проблема хронической венозной недостаточности (ХВН), осложняющей течение различных заболеваний вен, не имеет тенденции к разрешению, что обусловливает постоянный поиск оптимизации способов лечения и реабилитации пациентов с вышеуказанным синдромом. В статье приводится обзор современных исследований, посвященных проблеме коррекции ХВН. Особое внимание уделяется состоянию эндотелия при ХВН и возможностям коррекции эндотелиальной дисфункции с использованием биофлавоноидов, в частности, диосмина. Представлены результаты оригинального экспериментального исследования, посвященного особенностям функционального состояния эндотелия, эндотелиальной дисфункции и ее коррекции на фоне существующей ХВН.

Topics: Cardiovascular Agents; Chronic Disease; Diosmin; Endothelium, Vascular; Humans; Oxidative Stress; Treatment Outcome; Vascular Diseases; Venous Insufficiency

Inflammation represents an important epiphenomenon in the etiopathogenesis of chronic venous disease, a worldwide debilitating condition affecting millions of subjects. The pathophysiology of chronic venous disease (CVD) is based on the hemodynamic abnormalities in conjunction to alterations in cellular and extracellular matrix biocompounds. The endothelial dysfunction results from early perturbation in the endothelium linked to glycocalyx injury and promoted by inflammatory cells and mediators (such as matrix metalloproteinases and interleukins), which lead to progressive dilation of the vein resulting in chronic venous insufficiency. Activated leukocytes during the inflammatory process release enzymes, free radicals, chemokines and inflammatory cytokines in the vessel microenvironment, which are responsible for the changes of the venous wall and venous valve, reflux and venous hypertension, and the development/progression of tissue destruction and skin changes. Sulodexide, a highly purified mixture of glycosaminoglycans composed by 80% fast moving heparin and 20% of dermatan sulphate, exhibits anti-thrombotic and profibrinolytic properties, restoring also the essential endothelial glycocalyx. Glycosaminoglycan sulodexide has been also characterized to reduce the release of inflammatory cytokines/chemokines and to inhibit the matrix metalloproteinases-related proteolytic cascades, counteracting endothelial dysfunctions. The pleiotropic effects of sulodexide set the basis for a very promising agent in treating the spectrum of CVD.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Chronic Disease; Cytokines; Glycosaminoglycans; Humans; Inflammation Mediators; Signal Transduction; Treatment Outcome; Varicose Veins; Veins; Venous Insufficiency

Approximately 90% of German adults show alterations of their lower limb veins; about every fifth suffers from symptoms of chronic venous insufficiency (CVI). With compression therapy showing low compliance, CVI oedemas and accompanying subjective symptoms are frequently treated with anti-oedematous drugs of herbal origin. A guideline outlines the requirements for clinical studies with CVI drugs. Water displacement plethysmometry (volumetry) is the gold standard for determining the reduction ofoedemas. Besides reducing oedemas, drugs should also demonstrate effects on accompanying symptoms influencing quality of life. Despite assistance provided by the guideline, clinical studies in CVI are complex and subject to multiple error sources in planning and execution. The corroboration of successful studies in further confirmatory studies is good practice and demanded by regulatory authorities. This practice reduces the risk of drugs being accepted as effective just based on the play of chance. As an example, placebo controlled studies with an extract from red vine leaves show that a careful definition of patients as well as meticulous study planning and execution can reproducibly verify significant and clinically relevant treatment effects. When evaluating clinical studies it is recommended to refer to the CONSORT statement. Publications missing certain minimum information make interpretation difficult and may result in a biased judgment of the effects of therapy.

Topics: Biomedical Research; Cardiovascular Agents; Clinical Trials as Topic; Edema; Guidelines as Topic; Humans; Plant Extracts; Plethysmography; Venous Insufficiency

The aim of this study was to compare the reduction of venous ankle edema in randomized controlled trials of the main venoactive drugs versus a placebo or versus another venoactive drug and thereby to confirm or invalidate the existing recommendations on the pharmacological treatment of venous edema.. Publications of randomized controlled trials of venoactive drugs versus either a placebo or another venoactive drug on the reduction of ankle circumferences (AC) were searched through Medline and selected according to the Jadad and the Cucherat evaluation grids.. Ten publications dated between 1975 and 2009 including a total of 1010 patients were identified for the meta-analysis. Included were the following venoactive drugs: micronised purified flavonoid fraction (MPFF), hydroxyethylrutoside, ruscus extracts and diosmin. The mean reduction in AC was -0.80 ± 0.53 cm with MPFF , -0.58 ± 0.47 cm with ruscus extract, -0.58 ± 0.31 cm with hydroxyethylrutoside, -0.20 ± 0.5 cm with single diosmin, and -0.11 ± 0.42 cm with placebo. The reduction in AC was significantly superior to that of placebo whatever the drug concerned (P<0.0001). The comparison between MPFF, ruscus extract and hydroxyethylrutoside on the reduction of ankle edema was in favour of MPFF. This was significant (P<0.0001), while the efficacy of the latter two venoactive agents was comparable.. This meta-analysis confirms the validity of the grade A assigned to MPFF in the management of symptoms and edema in recent international guidelines.

Topics: Ankle; Cardiovascular Agents; Edema; Evidence-Based Medicine; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Veins; Venous Insufficiency

Topics: Cardiovascular Agents; Humans; Vascular Resistance; Veins; Venous Insufficiency

Chronic venous insufficiency (CVI) of the lower limbs is a major cause of morbidity and varicose veins affect 20% to 60% of adults in the western world. The treatment of patients with CVI attempts to reduce both clinical symptoms and the development of chronic venous disease. A meta-analysis using data from all clinical trials and studies of Cyclo 3 Fort, a combination of root extract of the Ruscus aculeatus plant (150 mg per capsule), hesperidin methyl chalcone (150 mg) and ascorbic acid (100 mg), was carried out to estimate the overall effect on the symptoms and severity of chronic venous insufficiency.. The meta-analysis included 20 placebo controlled, randomised, double blind studies and 5 randomised studies against a comparator drug. There were 6 single arm studies of Cyclo 3 Fort alone with no placebo arm. In all studies the response to Cyclo 3 Fort was compared to baseline values. In total there was information from 10,246 subjects.. On a 4 point symptom severity scale, where 0 corresponds to no symptoms and 3 to severe symptoms, Cyclo 3 Fort significantly reduces the severity of pain by 0.44 (0.12) points; cramps 0.26 (0.08), heaviness 0.53 (0.11), and paraesthesia 0.29 (0.10) compared to placebo. There is also a significant reduction in venous capacity of 0.70 (0.19) ml/100 ml with Cyclo 3 Fort compared to placebo. We also found reductions in the severity of oedema 0.43 (0.20) points, and decreases in calf and ankle circumference, 0.73 (0.37) cms and 1.17 (0.83) cm, respectively, among patients treated with Cyclo 3 Fort compared to placebo which were not statistically significant.. Despite questions surrounding the variability of data quality and sample size of some of the studies, we conclude that in patients with CVI Cyclo 3 Fort significantly reduces the severity of the symptoms compared to placebo. This study is a strong and objective demonstration of the clinical efficacy of Cyclo 3 Fort in treating patients with CVI.

Topics: Adult; Cardiovascular Agents; Chronic Disease; Humans; Plant Extracts; Treatment Outcome; Venous Insufficiency

An International Task Force made up of a panel of 16 experts has reviewed and objectively evaluated all aspects of chronic venous disease of the leg (CVDL). All available publications on CVDL from 1983 to 1997 were identified through computerized search in Medline and by a manual search. Next, three different screenings were performed in order to select only relevant papers providing a level of scientific evidence that was considered moderate to strong. Final conclusions and further therapeutic recommendations were made based on these publications. Medication, compression, local therapy, sclerotherapy, and surgery are the accepted available therapeutic options for CVDL. For edema, the following recommendations can be made: edema is an early sign of CVDL, but before starting any treatment, nonvenous causes of edema should be excluded. Medication and compression are the therapeutic options for edema that are accepted by the Task Force. Evaluation of their efficacy is based on objective measures of edema. Several well-conducted, placebo-controlled trials have shown efficacy of drugs such as micronized purified flavonoid fraction, rutosides, calcium dobesilate, and coumarin rutin. Graduated compression stockings have been shown to be effective; compression needs to be exerted at least at 35 mm Hg. Bandages, if properly applied, both fixed and stretched, can produce favorable results. Sclerotherapy or surgery is not indicated unless there is saphenofemoral or saphenopopliteal reflux. In the absence of such reflux or following deep venous thrombosis, there is no evidence to support sclerotherapy or surgery.

Topics: Anticoagulants; Bandages; Calcium Dobesilate; Cardiovascular Agents; Chronic Disease; Controlled Clinical Trials as Topic; Coumarins; Diosmin; Edema; Femoral Vein; Hemostatics; Humans; Leg; Placebos; Rutin; Saphenous Vein; Sclerotherapy; Vasodilator Agents; Venous Insufficiency; Venous Thrombosis

Topics: Cardiovascular Agents; Chemotherapy, Adjuvant; Combined Modality Therapy; Humans; Leg Ulcer; Randomized Controlled Trials as Topic; Venous Insufficiency

At the core of chronic venous insufficiency (CVI) is valvular incompetence affecting the large veins, which results in ambulatory venous hypertension. Recent research has revealed the pathophysiological stages involved: damage to the endothelium of the vein, leukocyte trapping and, finally, inflammatory reconstruction of the vessel wall. Lymphangiopathy involving the small and large lymph vessels is always present. One of the measures capable of influencing elevated venous pressure is compression therapy, which is discussed in detail in the present article. Drug treatment is a rational supplement to curative therapeutic approaches to chronic venous insufficiency that in mild-to-moderate cases, can result in an alleviation of symptoms similar to that achieved with compression therapy.

Topics: Bandages; Cardiovascular Agents; Combined Modality Therapy; Endothelium, Vascular; Humans; Leg; Microcirculation; Venous Insufficiency; Venous Pressure

Stenosis due to intimal hyperplasia and restenosis after initially successful percutaneous angioplasty are common reasons for failing arteriovenous fistulas. The aim of this study was to evaluate the effect of drug-coated balloons in the treatment of arteriovenous fistula stenosis.. Single-center, parallel group, randomized controlled trial. Block randomized by sealed envelope 1:1.. A total of 39 patients with primary or recurrent stenosis in a failing native arteriovenous fistulas were randomized to drug-coated balloon (n = 19) or standard balloon angioplasty (n = 20). Follow-up was 1 year. Primary outcome measure was target lesion revascularization.. In all, 36 stenoses were analyzed; three patients were excluded due to technical failure after randomization. A total of 88.9% (16/18) in the drug-coated balloon group was revascularized or occluded within 1 year, compared to 22.2% (4/18) of the stenoses in the balloon angioplasty group (relative risk for drug-coated balloon 7.09). Mean time-to- target lesion revascularization was 110 and 193 days after the drug-coated balloon and balloon angioplasty, respectively (p = 0.06).. With 1-year follow-up, the target lesion revascularization-free survival after drug-coated balloon-treatment was clearly worse. The reason for this remains unknown, but it may be due to differences in the biological response to paclitaxel in the venous arteriovenous fistula-wall compared to its antiproliferative effect in the arterial wall after drug-coated balloon treatment of atherosclerotic occlusive lesions. Trial registration: ClinicalTrials.gov NCT03036241.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon; Arteriovenous Shunt, Surgical; Cardiovascular Agents; Coated Materials, Biocompatible; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Paclitaxel; Prospective Studies; Renal Dialysis; Vascular Patency; Venous Insufficiency

Iliac vein stenting has emerged as the procedure of choice in the treatment of iliac vein obstruction (IVO). However, clinical outcomes have never been studied by a randomized clinical trial. Our purpose was to compare medical and endovascular treatment results in symptomatic chronic venous disease (CVD) patients with significant IVO documented by intravascular ultrasound (IVUS).. Patients with Clinical, Etiology, Anatomy, and Pathophysiology clinical class C3 to C6 and a visual analog scale for pain (VAS pain) score >3 were considered eligible. We randomly assigned limbs with ≥50% IVO on IVUS to undergo medical treatment alone or medical treatment plus iliac vein stenting. The patient and clinical physician were blinded. Primary outcomes included change from baseline in VAS pain score, Venous Clinical Severity Score, and 36-Item Short Form Health Survey quality of life questionnaire. Secondary outcomes included stent integrity, migration, and patency rates at 6 months.. Of 207 CVD patients, 58 (28%) were eligible and eight (14%) were excluded; 51 of 85 class C3 to C6 limbs (60%) had ≥50% IVO by IVUS. Iliac vein stenting, in randomized patients, was 100% technically successful. At 6 months' follow-up, the mean VAS pain score declined from a median of 8 to 2.5 in patients receiving stents and from 8 to 7 in patients receiving only medical treatment (P < .001). The Venous Clinical Severity Score dropped from a median of 18.5 to 11 after stenting and from 15 to 14 with medical treatment (P < .001). The 36-Item Short Form Health Survey (0-100) improved from a total median score of 53.9 to 85.0 with stenting and 48.3 to 59.8 after medical treatment (P < .001). There was no stent fracture or migration, and the primary, assisted primary, and secondary patency rates were 92%, 96%, and 100%, respectively (median, 11.8; range, 6-18 months).. Endovascular treatment of IVO with stenting is safe and promotes effective relief of symptoms and improvement in quality of life compared with medical treatment alone in symptomatic CVD patients. Our results echo those achieved in numerous previously published nonrandomized clinical series.

Topics: Adult; Aged; Angioplasty, Balloon; Cardiovascular Agents; Chronic Disease; Computed Tomography Angiography; Constriction, Pathologic; Double-Blind Method; Female; Humans; Iliac Vein; Male; Middle Aged; Multidetector Computed Tomography; Pain Measurement; Peripheral Vascular Diseases; Phlebography; Prospective Studies; Severity of Illness Index; Stents; Time Factors; Treatment Outcome; Ultrasonography, Doppler; Ultrasonography, Interventional; Vascular Patency; Venous Insufficiency

The aim of this study was to compare the clinical acceptability of two dose regimens of micronized purified flavonoid fraction (MPFF): a single 1000 mg tablet once daily versus 500 mg twice daily in patients suffering from chronic venous disease (CVD).. In an international, randomized, double-blind, parallel-group study, 174 patients (Clinical Etiological Anatomic Pathophysiologic [CEAP] class C0s to C4) were randomized to MPFF 1000 mg once daily or MPFF 500 mg twice daily for 8 weeks. Adverse events (AEs) were recorded in patient-kept diaries (weeks 0, 2, 4, 8) and leg pain was assessed using a Visual Analog Scale (VAS).. No serious AEs occurred. A total of 30 treatment-emergent adverse events (EAE) were reported (15 in each group). Three treatment-EAE in the MPFF 1000 mg group (constipation, dyspepsia, allergic dermatitis) were considered by the investigator to be related to treatment. All were of mild intensity and resolved when treatment finished. Both MPFF regimens were associated with a significant reduction in leg pain score with a reduction of 4.21 cm for MPFF 1000 mg once daily (P<0.001) and 4.01 cm for MPFF 500 mg twice daily (P<0.001). The reduction in pain was noted after 2 weeks of treatment and continuously throughout the treatment.. Both treatment regimens were well tolerated and associated with similar reductions in leg pain after 8 weeks of treatment. The new MPFF 1000 mg dose regimen has a similar safety profile to two MPFF 500 mg tablets with the advantage of one tablet per day and potential improved patient adherence.

Topics: Administration, Oral; Adult; Aged; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Drug Compounding; Female; Flavonoids; Humans; Male; Middle Aged; Pain; Pain Measurement; Russia; Serbia; Tablets; Time Factors; Treatment Outcome; Venous Insufficiency; Young Adult

Our current understanding of the pathophysiology of chronic venous disease (CVD) suggests that veno-active drugs (VAD) can provide effective symptom relief. Few studies have conducted head-to-head comparisons of VAD and placebo while also assessing objective measures (such as water plethysmography findings and tibiotarsal joint range of motion) and patient-reported quality of life outcomes.. To compare the effects of different VAD on limb volume reduction, tibiotarsal range of motion, and quality of life.. 136 patients with CVD (CEAP grades 2-5) were randomly allocated into four groups to receive micronized diosmin + hesperidin, aminaphthone, coumarin + troxerutin, or placebo (starch). Patients were administered a questionnaire consisting of a quality of life (QoL) measure designed specifically for persons with CVD, and underwent tibiotarsal joint angle measurement and water plethysmography of the lower extremity before and 30 days after pharmacological intervention. Assessors were blind to the treatment groups.. Nine patients dropped out of the trial. Data collected from the 127 remaining patients was considered for statistical analysis. There were no differences in tibiotarsal joint range of motion. Volume reductions ≥100 mL were more frequent in the diosmin + hesperidin group than in any other group. QoL scores were best in the aminaphthone group, and between-group differences were found on individual analysis of questionnaire items.. Use of VAD was associated with significant improvements in QoL as compared with placebo. VAD may be effective for providing symptom relief in patients with CVD.

Topics: Biomechanical Phenomena; Brazil; Cardiovascular Agents; Chronic Disease; Coumarins; Diosmin; Double-Blind Method; Drug Therapy, Combination; Edema; Female; Foot Joints; Hesperidin; Humans; Hydroxyethylrutoside; Male; para-Aminobenzoates; Plethysmography; Quality of Life; Range of Motion, Articular; Recovery of Function; Surveys and Questionnaires; Time Factors; Treatment Outcome; Venous Insufficiency

To determine the effect of aspirin on ulcer healing rate in patients with chronic venous insufficiency, and to establish prognostic factors that influence ulcer evolution.. Between 2001 and 2005, 78 patients with ulcerated lesions of diameter >2 cm and associated with chronic venous insufficiency were evaluated in our hospital. Of these, 51 patients (22 men, 29 women) with mean age of 60 years (range: 36-86) were included in a prospective randomized trial with a parallel control group. The treatment group received 300 mg of aspirin and the control group received no drug treatment; in both groups, healing was associated with standard compression therapy. During follow-up, held weekly in a blinded fashion, there was ulcer healing as well as cases of recurrence. Results were analyzed by intention-to-treat approach. Cure rate was estimated using Kaplan-Meier survival analysis, and the influence of prognostic factors was analyzed by applying the Cox proportional hazards model.. In the presence of gradual compression therapy, healing occurred more rapidly in patients receiving aspirin versus the control subjects (12 weeks in the treated group vs. 22 weeks in the control group), with a 46% reduction in healing time. The main prognostic factor was estimated initial area of injury (P = 0.032). Age, sex, systemic therapy, and infection showed little relevance to evolution.. The administration of aspirin daily dose of 300 mg shortens the healing time of ulcerated lesions in the chronic venous insufficiency (CVI). The main prognostic factor for healing of venous ulcerated lesions is the initial surface area of the ulcer.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Bandages, Hydrocolloid; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Combined Modality Therapy; Compression Bandages; Debridement; Drug Administration Schedule; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Spain; Time Factors; Treatment Outcome; Varicose Ulcer; Venous Insufficiency; Wound Healing

The aim of this study was to investigate the effect of a red-vine-leaf extract (AS195, Antistax(®), Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany) on the volume of the leg and clinical symptoms in patients with chronic venous insufficiency (CVI).. A multicentre, randomised, double-blind and placebo-controlled study was carried out with 720 mg AS195 per day over 12 weeks in CVI patients (CEAP Grades 3-4a) and moderate-to-severe clinical symptoms. Efficacy endpoints were changes in limb volume determined by water displacement volumetry, clinical CVI symptoms assessed on a 10-cm visual analogue scale and global efficacy evaluations.. The full-analysis set included 248 patients (placebo: n = 122; AS195: n = 126). After 12 weeks, AS195 significantly reduced lower limb volume by a mean of 19.9 standard error (SE) 8.9 ml over placebo (95% confidence interval (CI): -37.5, -2.3; p = 0.0268; analysis of covariance, ANCOVA). The standardised effect size of 0.28 for volume reduction indicates a clinically relevant effect. On Day 84, the symptom of 'pain in the legs' assessed by visual analogue scale decreased in the AS195 group compared with the placebo group: mean difference -6.6 SD 3.3 mm (95% CI: -13.1,-0.1; p = 0.047). Other symptoms showed no significant change. The tolerability of AS195 was similar to that of placebo.. AS195 treatment for 84 days resulted in an approximately 20 ml reduction of limb volume in the active treatment group compared with the placebo group. Patients reported subjective improvement following treatment with AS195 compared with placebo. However, patients' overall rating of efficacy did not correlate well with measured reductions in limb volume.. ClinicalTrials.gov NCT00855179.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Edema; Female; Germany; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebo Effect; Plant Extracts; Plant Leaves; Quercetin; Tablets; Time Factors; Treatment Outcome; Venous Insufficiency; Vitis; Young Adult

The aim of this study was to compare the change in functional signs of venous insufficiency and venous refilling time measured by mercury strain-gauge plethysmography under the effects of the combination of Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid (Cyclo 3 Fort).. An open-label clinical trial conducted in 65 women presenting with CEAP class C2s and C3s assessment criteria. At D0 and D28, functional signs were measured on a visual analog scale (VAS), venous refilling time by mercury strain-gauge plethysmography and venous reflux by echo-Doppler method.. Under treatment, venous refilling time increased from 11.7±4 s to 13.8±4.4 s with Δ of 26% (P<0.0001) and the percentage of patients showing improvement of functional symptoms ≥30% was significantly correlated (P=0.04) with the percentage of patients presenting an improvement in venous refilling time ≥10%.. Improvement in subjective functional signs under treatment with Cyclo 3 Fort was correlated with objective plethysmographic parameter improvement. There-fore, this study contributes to objectively document the benefit of prescribing this venoactive drug to active women with CEAP class C2s to C3s.

Topics: Activities of Daily Living; Analysis of Variance; Ascorbic Acid; Cardiovascular Agents; Chalcones; Chi-Square Distribution; Drug Therapy, Combination; Female; France; Hesperidin; Humans; Plant Extracts; Plethysmography; Predictive Value of Tests; Recovery of Function; Ruscus; Treatment Outcome; Ultrasonography, Doppler; Venous Insufficiency

This study was performed to test the hypothesis that the heparin and phosphatidylcholine (PDC) included in Aescin gel formulations had the main role of allowing a better penetration of Aescin without important pharmacodynamic effects. Heparin and PDC should be considered as "enhancers". They do not have - at the dosage used - a specific or independent action. An open, registry study of patients - a group with chronic venous insufficiency (CVI) and a group of patients with diabetic microangiopathy were completed.. In patients with CVI and in patients with diabetic microangiopathy, we used a commercial gel preparation containing Aescin, PDC and heparin (group A). The first group of patients used the full complex. The second group used the complex without PDC (group B) and the third (group C) used the complex without heparin.. In both studies the different groups of patients were comparable. In CVI patients (mean age 44.5; SD 2.4; range 40-50) venous microangiopathy was present at the perimalleolar region. Aescin produced comparable microcirculatory results with and without the two other components. Transcutaneus PO2 [TcPO2] increased in all groups. Transcutaneus PCO2 (TcCO2) decreases. The increased Laser Doppler Flux (LDF) (typical of CVI) decreased towards normality. The local Plasma Free Radicals [PFR] levels decreased as the result of better skin perfusion (P<0.05). Comparable data were observed in subjects with diabetic microangiopathy (mean age 46.5; SD 3.1). In these patients the compound was applied at the dorsum of the foot. TcPO2 increased with treatment. TcPCO2, skin flux and PFR decreased towards normal levels (P<0.05).. In conclusion Aescin improves the microcirculation and PFR. Heparin and PDC - included in the gel - have an ancillary role. An improved perfusion and nutrition of the skin was observed both in diabetic and venous microangiopathy. This may possibly contribute in the reduction of the incidence of ulceration associated with diabetic and venous microangiopathy. Aescin-based products may be included in a more complex management plan, including several systemic and local treatments.

Topics: Administration, Topical; Adult; Cardiovascular Agents; Diabetic Angiopathies; Escin; Female; Gels; Heparin; Humans; Male; Microcirculation; Middle Aged; Phosphatidylcholines; Registries; Treatment Outcome; Venous Insufficiency

The present study assessed the effect of Ruscus aculeatus, hesperidin methyl-chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders (CVD) in Latin American patients.. This study is an observational, single arm, multicentric and prospective trial. Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP) classes were included. Patient profiles, risk factors, clinical symptomatology and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were evaluated at inclusion and after 12-week treatment.. The main factors influencing the previous management of patients were age, gender, body mass index (BMI), familial history, physical activity, exposure to heat, heavy loads lifting, profession and clinical characteristics. All clinical symptoms significantly improved with treatment and, as BMI and CEAP classes increased. Ankle circumferences decreased over time, correlating with BMI and CEAP classes. The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class. The CIVIQ score significantly improved over time, correlating with age and CEAP classes.. A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD.

Topics: Adult; Aged; Argentina; Ascorbic Acid; Cardiovascular Agents; Chalcones; Chronic Disease; Drug Combinations; Female; Hesperidin; Humans; Logistic Models; Male; Mexico; Middle Aged; Odds Ratio; Plant Preparations; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Ruscus; Surveys and Questionnaires; Time Factors; Treatment Outcome; Venous Insufficiency

The RELIEF study (Reflux assEssment and quality of life improvement with micronized Flavonoids in chronic venous insufficiency [CVI]) is a prospective, controlled, multicenter, international study performed in patients with or without venous reflux. This study was conducted between March 1997 and December 1998 in 23 countries worldwide with the participation of more than 10,000 patients suffering from CVI. The European countries, the subject of this report, were represented by the Czech and Slovak Republics, Hungary, Poland, Russia, and Spain. The principal aims of the study were: 1. To validate the first quality-of-life scale specific to chronic venous insufficiency (CMVIQ) in different languages and to assess the evolution of quality of life in patients suffering from CVI, with or without venous reflux, treated with micronized purified flavonoid fraction (MPFF*) (1,000 mg/day). 2. To collect international epidemiologic data on venous reflux assessed with pocket Doppler and photoplethysmography. 3. To assess the evolution of symptoms and signs with a specific emphasis on edema through validated Leg-O-Meter measurement (heaviness, pain, cramps, sensation of swelling, edema) in patients suffering from CVI and treated with MPFF, 1,000 mg/day, during 6 months. The first country-by-country statistical analysis and the European consolidated analysis are now available. The CIVIQ questionnaires adapted to each participating country have been validated with highly significant validity and reproducibility (p<0.0001). All dimensions have demonstrated a highly significant and evolving improvement during the study. The results show several interesting findings concerning the epidemiologic data and, of these, two were particularly interesting: - More than 50% of patients suffering from CVI (class 0 to 4 of the CEAP classification) were reflux-free, which means that they were suffering from functional CVI. Patient distribution between the different classes of the CEAP classification changed in a statistically significant manner after 6 months' treatment with MPFF; the number of patients in the more severe classes decreased to the benefit of the less severe classes. Symptoms such as pain, leg heaviness, sensation of swelling, and cramps were significantly improved (p=0.0001). This was associated with a significant decrease in edema, when present, measured by leg circumferences with the Leg-O-Meter (p=0.0001). In conclusion, the European results of the RELIEF study showe

Topics: Cardiovascular Agents; Chronic Disease; Diosmin; Edema; Female; Humans; Leg; Male; Middle Aged; Muscle Cramp; Pain; Photoplethysmography; Prospective Studies; Quality of Life; Regional Blood Flow; Reproducibility of Results; Sensation; Ultrasonography, Doppler; Venous Insufficiency

Chronic venous insufficiency (CVI) is a common disorder associated with a variety of symptoms in later disease stages; despite the high prevalence of this pathology, suitable pharmaceutical therapies have not been explored to date. In this context, it was recently reported that a chronic increase in venous wall stress or biomechanical stretch is sufficient to cause development of varicose veins. Recent evidence demonstrate that flavonoids are natural substances that convey the circulatory system functionality, playing a key role in blood flow. Particularly, troxerutin, diosmin and horse chestnut extract, appear protective for the management of vascular diseases. The aim of the present study was to evaluate the effect of a flavonoid compound, containing troxerutin, diosmin and horse chestnut extract on in vitro model on HUVECs cells, due to its production of vasculoregulatory and vasculotropic molecules, on an ex-vivo model on mesenteric vessel contraction, to regularize mesenteric microcirculation and on in vivo model of CVI-induced by saphene vein ligation. Furthermore, the flavonoid compound capacity of extensibility and compatibility with peripheral veins was investigated through a tissue block culture study. The degree of absorption, the contractile venous activity, the histological analysis, the immunoistochemical and immunofluorescence evaluation for VEGF and CD34 were performed, together with inflammatory mediators dosage. For the first time, this research revealed the therapeutic potential of a compound, enriched with flavonoids, to be a supportive treatment, suitable to reduce varicose vein pathophysiology and to regularize venous tone.

Topics: Animals; Cardiovascular Agents; Cells, Cultured; Chronic Disease; Cytokines; Disease Models, Animal; Flavonoids; Human Umbilical Vein Endothelial Cells; Humans; Male; Mesenteric Veins; Mice; Nitric Oxide Synthase Type III; Saphenous Vein; Vascular Endothelial Growth Factor A; Vasoconstriction; Venous Insufficiency

Topics: Biopsy; Cardiovascular Agents; Debridement; Fasciotomy; Humans; Quality of Life; Skin; Stockings, Compression; Varicose Ulcer; Venous Insufficiency; Wound Infection

Topics: Cardiovascular Agents; Chronic Disease; Glycosaminoglycans; Humans; Treatment Outcome; Varicose Veins; Venous Insufficiency

The aim of this study was to evaluate the factors that limit the use of venoactive drugs (VADs), especially in patient with chronic venous disorders (CVD) noncompliant with compression therapy in a nationwide survey.. Analysis included 5134 CVD patients compliant with compression therapy and 4663 of those not accepting such method of therapy, participating in a large survey.. Venoactive drugs (VADs) and topical agents were used significantly less frequently by patients noncompliant with compression therapy compared to the compliant population (95.2% vs. 97.7%, P<0.001 and 70.1% vs. 79.9%, P<0.001, respectively). There were also less patients on two VADs concurrently in these subgroups (14.6% vs. 24.6%, P<0.001 respectively). Logistic regression analysis confirmed that noncompliant also have decreased adherence to Ruscus aculeatus extracts (OR=0.870), micronized purified flavonoid fraction (MPFF) preparations (OR=0.886), and topical agents (OR=0.877), but not horse chestnuts seed extracts. Coexisting obesity and other chronic illnesses were among the factors that decreased the use of Ruscus aculeatus extracts and micronized purified flavonoid fraction (MPFF) preparations. The use of topical agents was reduced with age, male sex, patients with coexisting chronic illnesses, obesity and adverse to accepting compression therapy. Additionally diuretics, antiplatelet agents and low-molecular weight heparins were less frequently used in the noncompliant population.. Patients who are not compliant with compression therapy are more frequently not adherent to pharmacological therapy. Coexisting obesity and other chronic illnesses demonstrate decrease in adherence to CVD pharmacotherapy.

Topics: Administration, Topical; Adult; Aged; Analysis of Variance; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Comorbidity; Drug Therapy, Combination; Female; Health Care Surveys; Humans; Logistic Models; Male; Medication Adherence; Middle Aged; Obesity; Odds Ratio; Poland; Risk Assessment; Risk Factors; Severity of Illness Index; Stockings, Compression; Venous Insufficiency

24th Annual Meeting of the American Venous Forum Orlando, FL, USA, 8-11 February 2012: The American Venous Forum unites authorities on all facets of venous disease, the pathophysiology of venous disease and its treatment. The goal of this meeting was to educate attendees about current and novel clinical strategies to effectively manage venous disease.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Humans; Pharmacology, Clinical; Stents; United States; Vascular Diseases; Venous Insufficiency

The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE 1) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C(2); GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration ≥500 ms, vein diameter ≥3.5 m

Topics: Cardiovascular Agents; Compression Bandages; Endovascular Procedures; Evidence-Based Medicine; Humans; Patient Selection; Predictive Value of Tests; Recurrence; Risk Assessment; Sclerotherapy; Severity of Illness Index; Societies, Medical; Treatment Outcome; United States; Varicose Veins; Vascular Surgical Procedures; Venous Insufficiency

Congenital anomalies of the inferior vena cava is an extremely rare vascular anomaly with controversial pathogenesis. Anomalies of the inferior vena cava (IVC) are present in 0.3% to 0.5% of otherwise healthy individual and in 0.6% to 2% of patients with other cardiovascular defects. The phenomenon of absence of the IVC has been described in a variety of ways such as absence, agenesis, anomalous, and interruption of a particular segment ([infra] hepatic, prerenal, renal, or infrarenal) of the IVC. We describe a 42-year-old man with chronic venous insufficiency, without DVT, caused by congenital absence of renal segment of the IVC.

Topics: Adult; Cardiovascular Agents; Chronic Disease; Combined Modality Therapy; Diosmin; Exercise Therapy; Humans; Male; Phlebography; Stockings, Compression; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color; Vena Cava, Inferior; Venous Insufficiency

Topics: Cardiovascular Agents; Chronic Disease; Compression Bandages; Evidence-Based Medicine; Humans; Sclerotherapy; Treatment Outcome; Varicose Ulcer; Vascular Surgical Procedures; Venous Insufficiency; Wound Healing

The aim of this independent study was to demonstrate the rapidity of the efficacy of an oral venotropic compound (Linfavenix, including natural elements) in patients with chronic venous insufficiency (CVI). Two groups of patients with chronic venous insufficiency (CVI) ankle swelling) were treated with Linfavenix or with below-knee elastic compression. The average ambulatory venous pressure (AVP) at inclusion (both groups)was 56.2 (range 48-55) with a refilling time (RT) shorter than 10 seconds. These parameters indicated a severe level of venous hypertension. There were no significant differences in AVP and RT between the two groups. The two groups of subjects with CVI were comparable; in the Linfavenix group there were 14 patients (age 44.5; sd 4; range 34-55; 7 females); in the elastic compression group there were 12 patients (45.4;5; range 36-56; 7 females). The clinical picture and microcirculatory parameters at inclusion were comparable. RF was comparable at inclusion in the two groups. At two weeks, the differences in RF (between goups) were not significant (the flux decreased in both groups, indicating improvement) while at 4 weeks the difference was larger (but non significant between the two groups) with a significant decrease in RF in the Linfavenix group. The RAS was also comparable at inclusion. Both groups had a significant decrease at 2 and 4 weeks. The decrease produced by Linfavenix after 4 weeks in RF was larger and significant (p<0.05) in comparison with the elastic compression group. Also the differences observed in ASLS were significant in both groups with an important, significant difference in favour of Linfavenix at 4 weeks (op<0.05) visibile as edema reduction. The decrease in edema was relevant in both groups at 2 (p<0.05) and 4 weeks (p<0.05) with a minimal but significant difference (p<0.05) between the Linfavenix and the elastic compression group. These variations in microcirculatory parameters indicate that the treatment with Linfavenix is, in its microcirculatory efficacy, at least comparable than elastic compression with is considered a standard therapeutic option in these patients. A significant level of improvement was reached with Linfavenix, in most patients (10/14) at 2 weeks for RF, at 7 days for the RAS and also at 2 weeks in almost all patients (13/14) considering ASLS and edema. No side effects due to treatment were observed. Compliance and tolerability were very good (no patient had to stop treatment; there were n

Topics: Adult; Aesculus; Ankle; Cardiovascular Agents; Chronic Disease; Drug Combinations; Fagaceae; Female; Hamamelis; Humans; Male; Middle Aged; Nuts; Phytotherapy; Plant Preparations; Pyrus; Ruscus; Sorbus; Stockings, Compression; Thrombotic Microangiopathies; Treatment Outcome; Vaccinium myrtillus; Venous Insufficiency

To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response.. A femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100 mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP).. The acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals.. Venous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension.

Topics: Animals; Arteriovenous Shunt, Surgical; Blood Flow Velocity; Cardiovascular Agents; Chemotaxis, Leukocyte; Diosmin; Disease Models, Animal; Edema; Femoral Artery; Femoral Vein; Granulocytes; Lymphocytes; Macrophages; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Wistar; Regional Blood Flow; Saphenous Vein; Stress, Mechanical; Time Factors; Venous Insufficiency; Venous Pressure

Topics: Cardiovascular Agents; Catheter Ablation; Chronic Disease; Diagnostic Imaging; Endoscopy; Humans; Leg Ulcer; Ligation; Lower Extremity; Microcirculation; Sclerotherapy; Stockings, Compression; Varicose Veins; Vascular Surgical Procedures; Venous Insufficiency; Venous Thrombosis

Several phlebotropic drugs, or edema-protecting drugs, are available, the most important of which are found in the gamma-benzopyrone family (flavonoids). gamma-Benzopyrones can be plant extracts, semisynthetic preparations, or synthetic preparations. This family is divided into two different groups: flavones and flavonols, and flavanes (flavanones). The flavone group contains various types of molecule and includes diosmin. Here we discuss the pharmacologic aspects in edema associated with chronic venous insufficiency (CVI) of one of the reference phlebotropic drugs, micronized purified flavonoid fraction (MPFF), a semisynthetic preparation from the diosmin group, which represents the latest improvement in flavonoid formulation. Before we detail the pharmacologic aspects, a brief summary of the pathophysiology of edema in CVI is necessary. Several factors are implicated: the veins, which create the conditions favorable to edema; the microcirculation, which is the site of fluid transfer into the interstitial tissue; and the lymphatics, which have a limited possibility to reduce edema. Major discoveries are currently being made in CVI and the microcirculation. Results of studies show that MPFF decreases capillary permeability and increases capillary resistance, which could partly be explained by inhibition of leukocyte activation, migration, and adhesion. This inhibition is linked to a significant decrease in plasma levels of endothelial adhesion molecules (VCAM-1 and ICAM-1) after MPFF treatment. Thus, the CVI-induced damage to the microcirculation is counteracted by MPFF. The lymphatic system is also improved by MPFF treatment. The lymphagogue activity of MPFF has been demonstrated in experimental animal models and confirmed by microlymphographic measurement in patients suffering from severe CVI. The pharmacologic activity of MPFF in lymphedema was observed in a study using an animal model of acute lymphedema and in a study in patients with upper limb lymphedema secondary to breast cancer treatment. All these findings point to the importance of acting on each factor involved in the formation and maintenance of edema. This pharmacologic activity is indeed reflected by the clinical efficacy on edema observed during treatment with MPFF.

Topics: Animals; Capillary Permeability; Capillary Resistance; Cardiovascular Agents; Chronic Disease; Coumarins; Diosmin; Disease Models, Animal; Edema; Flavonoids; Humans; Intercellular Adhesion Molecule-1; Leukocytes; Lymphatic System; Lymphedema; Microcirculation; Vascular Cell Adhesion Molecule-1; Veins; Venous Insufficiency

Reversible aggregation of red blood cells (RBC) plays an important role in determining blood flow properties, and it is this aggregation which increases blood viscosity at low shear rates. The structure and sites of venous thrombi, as well as the fact that stasis is a major predisposing factor in venous thrombosis, suggest a strong association between vein thrombosis, slow blood flow and increased blood viscosity. RBC aggregation and disaggregation were measured (SEFAM erythroaggregameter, France) in 54 patients with a history of unexplained leg vein thrombosis. Results were compared to those of controls classified according to age. Increased RBC aggregability was observed in 41% of the patients, and the mean values indicated a significant elevation of RBC aggregability in patients when compared with controls (P < 0.05). Subgroups were compared to study the influence of thrombus recurrence and thrombosis type (deep versus superficial vein thrombosis) on the aggregation parameters. No significant difference was found between these subgroups. The use of compression stockings and veinotropic drugs tended to reduce the abnormalities in RBC aggregability (P < 0.05). An increase in RBC aggregability and in the shear resistance of RBC aggregates, by predisposing to circulatory stasis, is likely to contribute to the evolution and complications of leg vein thrombosis.

Topics: Adult; Bandages; Blood Viscosity; Cardiovascular Agents; Chronic Disease; Erythrocyte Aggregation; Female; Fibrin; Hematocrit; Humans; Leg; Male; Middle Aged; Thrombophlebitis; Venous Insufficiency

The authors tryed by a statistical study to evaluate the efficacy of aphlebotinic therapy in venous diseases induced or aggravated by estroprogestative contraception. During this study, it emerged that the induced functional venous problems were quite virtually corrected by this treatment.

Topics: Adult; Anthocyanins; Ascorbic Acid; Cardiovascular Agents; Contraceptives, Oral, Hormonal; Drug Combinations; Female; Humans; Leg; Lithium; Saponins; Thrombophlebitis; Time Factors; Varicose Veins; Venous Insufficiency

Topics: Adenosine; Alkanesulfonates; Ascorbic Acid; Cardiovascular Agents; Chronic Disease; Drug Combinations; Hemorrhoids; Humans; Rutin; Venous Insufficiency

Topics: Cardiovascular Agents; Diosmin; Female; Hemorrhoids; Humans; Intrauterine Devices; Menorrhagia; Menstruation Disturbances; Metrorrhagia; Pregnancy; Pregnancy Complications, Cardiovascular; Uterine Hemorrhage; Varicose Veins; Venous Insufficiency