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

Video Abstract.

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

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

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

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

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

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

Impact of chronic venous disease on quality of life: Results of vein alarm study.

Chronic venous disease (CVD) affects millions of people and negatively impacting the patient's quality of life (QoL) and most of the patients are diagnosed with CVD in advanced stages. The impact of newly diagnosed CVD on QoL has not been evaluated by other studies in Romania. The aim of this study was to assess the QoL for adult patients newly diagnosed with CVD addressing to the General Practitioner's (GP) office in Romania between June to August 2016. Patients included in the study were adult, signing the inform consent form, newly diagnosed with CVD or patients diagnosed with CVD, without CVD treatment the past 6 months. Data on demographic distribution, risk factors, clinical profiles, CVD symptomatology, QoL parameters, as well as pharmacological management practice were collected. The study included 1,893 patients (79.08% females) with 50.4% of patients in the age group 51-70 years. The most frequent CVD symptoms reported, were heavy leg sensation (85.74%), swelling of the feet (77.28%) and pain (73.11%). The most frequent CVD signs were telangiectasia and reticular veins (79.19%), varicose veins (65.77%) and edema (53.35%). The clinical, aetiological, anatomical and pathophysiological (CEAP) classification placed most of the patients in C3 class (31.85%), followed by C2 class (28.00%), C1 class (21.02%) and C4a (8.87%). Most of the patients reported 'low' or 'moderate' intensity of the CVD symptoms. QoL was affected for most of the patients at 'a mild' or 'moderate' degree, being noticed as a significant negative impact on physical, psychological, and social functioning components of QoL, correlated with CEAP class (P<0.001). Data regarding correlation of CEAP class, CVD symptoms and impact on QoL identified a significant correlation between all analyzed components (P<0.001). Study results prove that CVD diagnosis was established with relative delay and CVD is negatively affecting patients' QoL. Additional research will be needed to identify the long-term impact of CVD on QoL of the affected patients and their families.

Epidemiology and clinical characteristics of chronic venous disease in Romania.

Chronic venous disorder (CVD) is a complex disease, that affects millions of people worldwide, and due to the fact that in its early stages is often overlooked by healthcare providers and ignored by the patient, the assessment of incidence and prevalence of CVD is difficult to be made. The aim of this project was to assess the CVD prevalence, risk factors and clinical characteristics in the adult population in Romania. A cross-sectional survey was carried out in Romania from June 2015 to July 2015, including 185 general practitioners (GPs). Data regarding patient characteristics, risk factors, family medical history, CVD signs and symptoms, C-classification, and pharmacological management of CVD were collected. The study included 7,210 patients, predominantly female (71.0%), with the mean age of 58.2 years. Within the study population, 2,271 (31.5%) patients had already the CVD diagnosis established prior to the study visit, while for 2,664 (36.9%) patients, CVD was diagnosed during the visit, while for the rest of the patients, 2,275 (31.6%), CVD diagnosis was not established prior or during the study visit. Age, female, sex and previous pregnancies were major risk factors for developing CVD. The newly diagnosed CVD rate was 36.9% and the directly calculated CVD prevalence in June-July 2015 was 68.4%, while the indirectly calculated CVD prevalence was 80.7%. CVD is a very common disease, with a prevalence of CVD within the study population in June-July 2015 of 68.4%. The newly diagnosed CVD cases represent 36.9% of patients included in this study, nevertheless both parameters could be underestimated, as long as a significant percentage of patients presenting symptoms, but no CVD signs, were not considered by GPs as CVD cases.