Clinical Decisions in the Absence of Evidence: Expert’s Panel Recommendations for the Management of Chronic Venous Disease and Superficial Thrombophlebitis

Venous appropriate use criteria are an important step in improving the quality of chronic venous disease care

Presidential address: Venous disorders—Reflections of the past three decades

Background/Objectives: Chronic venous disease is a very common disease. Recent studies suggest a potential link between this condition and cardiovascular disease or mortality. Common pathophysiological features include endothelial injury, hypercoagulability, and systemic inflammation. Conservative management of chronic venous disease includes compression therapy and pharmacological treatment. However, there is some controversy regarding the exact place of pharmacological treatment in the management of this condition. We conducted the VeinHeart Survey to gather information on the management of patients with chronic venous disease referred to vascular specialists in Italy. Methods: The present survey involved 78 Italian phlebologists, angiologists, and vascular surgeons, with data from a total of 1621 patients. Results: Drug therapies prescribed by vascular specialists participating in this survey included: glycosaminoglycans, topical phlebotonics, systemic phlebotonics, and supplements. The most commonly prescribed medications were glycosaminoglycans, both at the first visit and at follow-up. The meantime since the first visit was 56.4 days. Both symptoms and signs improved at follow-up. The most improved signs at follow-up were edema and venous ulcer healing. The prevalence of CEAP classes C3 and C4 also showed a decrease at the follow-up visit. Conclusions: The findings of this survey provide a picture of the state of the art of current pharmacological treatments prescribed by expert clinicians in the management of patients with chronic venous disease in Italy. This may offer some useful insights for the optimization of current therapeutic options, in order to improve the clinical management of this disease.

Scope A systematic review of the clinical literature concerning medical management of chronic venous disease with the venoactive therapy Micronized Purified Flavonoid Fraction was conducted in addition to an investigation of the hemodynamics and mechanism of chronic venous disease. Methods The systematic review of the literature focused on the use of Micronized Purified Flavonoid Fraction (diosmin) which has recently become available in the US, in the management of chronic venous disease. The primary goal was to assess the level of evidence of the role of Micronized Purified Flavonoid Fraction in the healing of ulcers, and secondarily on the improvement of the symptoms of chronic venous disease such as edema. An initial search of Medline, Cochrane Database for Systematic Reviews and Google Scholar databases was conducted. The references of articles obtained in the primary search, including a Cochrane review of phlebotonics for venous insufficiency, were reviewed for additional studies. Studies were included if patients had a diagnosis of chronic venous disease documented with Doppler and Impedance Plethysmography. Studies excluded were those that had patients with arterial insufficiency (Ankle Brachial Index < .6), comorbidity of diabetes, obesity, rheumatological diseases, or if other causes of edema were present (congestive heart failure, renal, hepatic or lymphatic cause), or if the patient population had recent surgery or deep vein thrombosis, or had been using diuretics (in studies of edema). Other elements of the study design were to note specifically the type of compression therapy used in conjunction with Micronized Purified Flavonoid Fraction. Results The literature review yielded 250 abstracts, 65 of which met criteria for further review and 10 papers were selected for consideration in the systematic review. Conclusion In summary, the general level of evidence supports the recommendation that the use of medical therapy with Micronized Purified Flavonoid Fraction has beneficial outcomes without serious adverse events. In the United States, diosmiplex is the only available prescription formulation of Micronized Purified Flavonoid Fraction. It is derived from the rinds of oranges and is categorized as a medical food and not as a drug; and may be a particularly attractive therapy for many chronic venous disease patients because of its favorable safety profile. The Working Group for chronic venous disease concurs with previous guidance by the International European Society for Vascular Surgery in 2015 which recommended the use of Micronized Purified Flavonoid Fraction for the healing of venous ulcers, alone and adjunctive to compression therapy, and for the reduction in symptoms of chronic venous disease such as edema.

Introduction: Other entities besides deep vein thrombosis (DVT) affecting the venous system, such as superficial vein phlebitis (SVP) and superficial vein thrombophlebitis (SVT), receive poor attention in the literature. However, both entities may propagate proximally into the deep venous system and progress to a DVT. To our knowledge, the relevance of other venous findings such as SVP or SVT in coronavirus disease 2019 (COVID-19) patients has not been evaluated. This work aimed to assess the clinical, biochemical, and hematological variables associated with the incidence of acute venous diseases, such as DVT, SVP, and SVT, in a cohort of 74 critically ill COVID-19 patients and their association with mortality.Methods: Given the high thrombotic risk, all patients underwent venous imaging with bedside ultrasound. Clinical variables were obtained from medical records. Comparisons were made by the chi-square test or Fisher’s exact test. We constructed Kaplan-Meier curves and used Cox proportional hazard models to calculate hazard ratios for dichotomized risk factors to identify predictors of mortality. SPSS version 21.0 (IBM Corp., Armonk, NY) was used for statistical analysis.Results: SVP occurred in 28 patients (37.8%), DVT in 22 patients (29.7%), and 28 patients died (37.8%). Elevated D-dimer was associated with DVT but not with SVP. Neither SVP nor DVT was associated with mortality. After adjusting for age, elevated troponins (OR: 2.4, 95% CI: 1.1-5.4), platelets < 244 cell/mm3 (2.4, 1.1-5.6), and IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) bleeding score > 7 (2.8, 1.3-6.3) were predictors of mortality.Conclusions: Acute venous findings such as SVP and DVT are highly prevalent and independent of mortality in critically ill COVID-19 patients. These entities are not related, although they may occur synchronically. DVT is frequently presented as an asymptomatic distal bilateral finding associated with elevated D-dimer, decreased ferritin, and higher vasoactive drug use but independent from chronic venous disease. Interestingly, elevated troponins, decreased platelets, and a prognostic value > 7 of the IMPROVE bleeding score were predictors of mortality in this group of critically ill COVID-19 patients.

Atrial fibrillation (AF) and chronic venous disease of the lower extremities (CVD) are common. Risk factors for both these diseases are often similar. AF and CVD can lead to thromboembolic complications, and anticoagulation is used to prevent these events. Objective. To assess the risk of venous thromboembolism and potential risk factors among women with AF and CVD of the lower extremities receiving direct oral anticoagulants (DOACs). Material and methods. A prospective cohort study included 55 women (mean age 71 years). The main group included 28 patients with C2-C6 CVD, the control group — 27 women without CVD or with C0-C1 disease. All patients received DOACs for AF. Incidence of venous thromboembolism was estimated throughout 12-month period. Results. Venous thrombosis occurred in 3 patients (5.5%). One patient had deep vein thrombosis, 2 patients — superficial vein thrombophlebitis. All cases were registered in the main group (p=0.237). Smoking (p=0.006), obesity (p=0.037), chronic heart failure and hypothyroidism (p=0.048 and p=0.041) were more common in women with thrombotic events. Serum thyroid-stimulating hormone and C-reactive protein were also higher (p=0.008 and p=0.041). Incidence of venous thromboembolic events was higher in patients with chronic venous insufficiency (p=0.002). Conclusion. Women with AF receiving DOACs have a higher risk of venous thromboembolic events in case of concomitant CVD, obesity, hypothyroidism, chronic heart failure, elevated serum CRP and TSH.

Superficial vein thrombophlebitis (STP) is a common inflammatory-thrombotic process that may occur spontaneously, after a trauma or as a complication after medical or surgical interventions (1, 2, 6). In most of the cases it is a sterile inflammation of the vein wall and the surrounding tissue, accompanied by intravenous thrombosis. In the rare cases of infectious superficial thrombophlebitis, the infection is introduced inside the veins, mostly after venous manipulations, by insects, traumatism or furunculosis.The frequency of the disease is higher at women, probably because of pregnancy and the high rate of varicosis. The superficial thromboflebitis affects all the ages (from 18 to 87), but is most frequent between 50 and 60 years for men and women.In a nine years period, since 01.01.2009 to 31.12.2017, 495 patients were treated by STP in Military medical Academy. They were divided in two groups. 108 (22%) patients from the first group, were admitted for surgery. The other group of 387 patients underwent conservative therapy.The goals of therapy for superficial thrombophlebitis are to prevent progression into the deep venous system and to hasten the resolution of the inflammatory and thrombotic processes in areas already involved.The nonsteroidal antiinflammatory and venotonical drugs, low molecular weight heparin and nonsteroidal creams for local aplication are the first options. In the rear cases of infectious thromboflebitis, the antibiotics are applied. When the thromboplebitis of the saphenous veins reaches the saphenofemoral (SFJ) or saphenopopliteal (SPJ) junction, or cloth reaches the iliac veins, the surgical treatment is suggested.

VSICON 2018 Prize Paper Abstracts

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

Chronic Venous Disease Treated by Ultrasound Guided Foam Sclerotherapy

Trends In the Epidemiology and Management of Chronic Venous Disease In the UK

Chronic Venous Insufficiency

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

Despite continuous improvement in our knowledge and management of chronic venous disease (CVD), certain areas, such as the role of muscarinic receptors in the pathology and treatment of CVD, remain unexplored. The symposium "The place of Ruscus extract, hesperidin methyl chalcone, and vitamin C in the management of CVD", held at the Annual Meeting of the European Venous Forum on 7-9 July 2016 in London, presented an update on the pathophysiology of CVD and highlighted how the combination of Ruscus extract, hesperidin methyl chalcone, and vitamin C (Ruscus/HMC/VitC; Cyclo 3® Fort), may counteract the deleterious processes underlying CVD. The data presented during this symposium are reported here. The pathophysiology of CVD is driven by a complex process involving numerous factors, with the two key players being venous hypertension and the inflammatory response. The cascade of reactions induced by disturbed venous flow, inflammation, and tissue alterations results in the early appearance of symptoms and progressive development of clinical signs of disease. Previous studies have shown that Ruscus extract acts at three levels: on the veins, capillaries and lymphatics, and has anti-inflammatory properties. A series of recent experiments has shed new light on the mechanism of action of the combination of Ruscus/HMC/VitC. The efficacy of Ruscus/HMC/VitC in CVD is supported by clinical studies, while two meta-analyses have confirmed a significant decrease of several symptoms and ankle circumference in response to treatment with this agent, leading to the conclusion that Ruscus/HMC/VitC deserves a Grade A rating.

The relationship between increased body mass index and primary venous disease severity and concomitant deep primary venous reflux.