The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

I.A. Zolotukhin

Pirogov Russian National Research Medical University

Yu.M. Stoyko

N.I. Pirogov National Medical and Surgical Center

I.A. Suchkov

Ryazan State Medical University

O.V. Golovanova

Pirogov Russian National Research Medical University

O.I. Efremova

Pirogov Russian National Research Medical University

A.N. Kuznecov

Pirogov National Medical and Surgical Center

A.V. Tsyplyashchuk

N.I. Pirogov National Medical and Surgical Center

A.A. Kamaev

Ryazan State Medical University

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


I.A. Zolotukhin, Yu.M. Stoyko, I.A. Suchkov, O.V. Golovanova, O.I. Efremova, A.N. Kuznecov, A.V. Tsyplyashchuk, A.A. Kamaev

More about the authors

Journal: Journal of Venous Disorders. 2023;17(1): 26‑33

Views: 1573

Downloaded: 110

To cite this article:

Zolotukhin IA, Stoyko YuM, Suchkov IA, Golovanova OV, Efremova OI, Kuznecov AN, Tsyplyashchuk AV, Kamaev AA. Venoactive Drug Treatment or Compression Stockings in Warm Weather Season in Symptomatic Patients with Chronic Venous Disease. Journal of Venous Disorders. 2023;17(1):26‑33. (In Russ., In Engl.)

Recommended articles:
Compliance with 15—20 mm Hg Compression Pantyhose in Female Patients with C0S-C2S Chro­nic Venous Disease. Journal of Venous Diso­rders. 2023;(1):18-25
Exte­nded Compression Decreases Hype­rpigmentation Rate after Scle­rotherapy in Patients with Spider Veins and Tela­ngiectasias. Journal of Venous Diso­rders. 2023;(1):34-40
Compression After Scle­rotherapy in C1 Patients: Impact on Outcomes and Complications Rate. Journal of Venous Diso­rders. 2023;(4):343-351
Hesperidin: Pote­ntial but Unde­restimated Oppo­rtunities. Journal of Venous Diso­rders. 2023;(4):352-360
The Effect of 18—21 mmHg Compression Knee Socks on Venous Symptoms in Patients with Chro­nic Venous Diseases: a Randomized Controlled Trial (GOLIATH). Journal of Venous Diso­rders. 2024;(1):32-36
Adhe­rence to the guidelines for the treatment of sepsis in children in pediatric inte­nsive care units. Russian Journal of Anesthesiology and Reanimatology. 2023;(4):35-41
Rela­tionship of patients with multiple scle­rosis to vaccination against COVID-19. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(7-2):29-33
Features of pharmacotherapy of vascular cognitive impairment in the elde­rly. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;(9):15-20
Successful combinations of drug and non-drug therapy for low back pain. Russian Journal of Pain. 2024;(1):57-67


Chronic venous disease (CVD) is a wide-spread condition that affects more than 50% adults. Minimally invasive treatment such as sclerotherapy and endovenous thermal ablation are the common methods for managing CVD patients [1—3]. Beyond invasive procedures many patients receive recommendations to use compression stockings and/or venoactive drug therapy. Compression therapy is considered a basic tool for improving venous return and hemodynamics and to reduce the severity of CVD [1—4]. Compression is prescribed widely regardless of presence or absence of CVD symptoms or venous edema. At the same time, medical therapy has a very clear indications which include venous symptoms, edema and trophic disorders [1, 2, 5].

Effectiveness of CVD treatment can be significantly affected by low adherence of patients to physician’s prescriptions, which is very important for compression therapy in particular [6—8]. Physicians involved in the management of patients with CVD are well aware that many of them are poorly compliant with compression regimen. Moreover, in the warm season, patients often stop using compression, even though they are strongly advised not to stop using stockings. Patient's non-compliance during this period of the year is mainly related to a significant discomfort from compression garment [8]. Alternative administration of VAD treatment alone i.e., without prescribing compression may be a good option for CVD patient in a warm weather condition. While searching literature databases we failed to find studies that confirm this practical approach.

Aim — to establish an effect VAD treatment alone in symptomatic CVD patients in a warm season and to compare effect of medical treatment with routinely prescribed compression therapy results.

Material and methods

We conducted a comparative, non-randomized, multicenter study on 60 symptomatic CVD patients.

Inclusion criteria

The inclusion criteria were age 18 > years, C1S, C2S, C3S classes according to the basic CEAP, patient's ability to follow the procedures, signed informed consent.

Exclusion criteria

The exclusion criteria were C0, C1A, C2A, C3A, C4A/S, C5A/S, C6A/S disease; any regular treatment for CVD two months before inclusion, any venous intervention planned during follow-up, medical therapy with other VAD during follow-up, use of compression stockings for patients in the VAD therapy group, contraindications to VAD therapy, pregnancy, lactation.

Study groups

VAD group included patients who were prescribed with a micronized diosmin 900 mg and hesperidin 100 mg (Angiorus, Sintez PJSC, Russian Federation) one tablet OD for 90 days. Patients of VAD group were supplied with a drug for the whole treatment course. Compression group included patients who were recommended to class one or two compression stockings, depending on the CVD class for 90 days, 5 days a week, 8 hours a day. The recruiter prescribed compression treatment according to personal clinical experience and explained to the patient compression importance, regimen and possible adverse effects.

Patients’ allocation into groups was at the discretion of the recruiter, while maintaining a ratio of 2:1. Patients were recruited from May to June 2022. Thus, the follow-up period fell on the hot season.

Data collection

Patients were examined clinically and by duplex ultrasound. Demographic information and medical history were taken. CVD was descripted with basic CEAP classification. Leg’s discomfort related to venous symptoms and presence/absence of venous pain, fatigue, heaviness, sensation of swelling and night cramps, QoL were registered.


The primary end-point was the change in leg’s discomfort caused by venous symptoms. The secondary end-points were QoL, rates of venous pain, fatigue, heaviness, sensation of swelling and night cramps. We also registered adherence to treatment and rates of adverse events. If both legs were affected the outcomes were assessed on the leg with a more severe discomfort.

Recreational activity of patients during follow-up period was registered also. Patients were asked if they were on a vacation and if yes, for how many days and of what kind the holiday were (relaxing or active). These data were collected in order to find possible differences between groups. This have been based on observations from real-life practice that shows a decrease in severity of venous symptoms in patients with CVD during the holiday period, even in the absence of regular treatment.

Assessment tools

Leg’s discomfort was measured by VAS. QoL was assessed with CIVIQ-20 questionnaire.


The study protocol included three visits: visit 1 — selection of the patient, start of the treatment; visit 2 — a phone call between 31 and 60 day after treatment start to collect information on adherence and adverse events; visit 3 — end-of-study visit, at 90th day (±1—2 days).

Adherence to treatment

Beyond the information on adherence collected during visit 2 a diary completed by patient was assessed in VAD group at visit 3. In the compression group patients were asked if they were adherent to regimen prescribed or not.

Protocol approval

The study protocol was approved by the Pirogov Russian National Research Medical University (No. 217, 18.04.2022), Pavlov Ryazan State Medical University (No. 14, 11.04.2022), Pirogov National Medical and Surgical Center (No. 4, 20.04.2022). The protocol was registered in the Russian CVD Treatment Registry, No.RRT_CVD 7.013.

Statistical analysis

Data are presented as absolute and relative values (%), mean and standard deviation. Quantitative variables between groups were compared with Mann-Whitney test. Qualitative variables were compared with Fisher's exact test. To compare paired nominal values McNemar's test was used. Open-sourced online statistics calculators were used. Significance level was set at p<0.05.


41 patients were included in the VAD group, 19 in the compression group (Table 1). No significant differences were found in main characteristics. One patient with C4 was included in every group. Given the small number of these patients and their distribution into every group we decided not to exclude them from analysis.

Table 1. Characteristics of patients


VAD group (n=41)

Compression group (n=19)









12 (29%)

8 (42%)


29 (71%)

11 (58%)

Body mass index, kg/m2





28 (68%)

16 (84%)


Not working

13 (32%)

3 (16%)

Personal CVD history, years




Family history of CVD

30 (73%)

14 (73%)


Both legs affected

14 (34%)

3 (15.8%)





6 (14.6%)

2 (10.5%)


15 (36.6%)

12 (63.2%)


19 (46.4%)

4 (21%)


1 (2.4%)

1 (5.3%)

Legs discomfort at baseline, VAS, mm




All patients attended last visit. 29 (71%) patients of the VAD group and 16 (84%) of the compression group (p=0.346) were on a vacation during follow up. At the same time, patients from the VAD group spent vacation actively significantly less frequently than compression group patients: 3 and 7, respectively (p=0.008).

The dynamics of the outcomes are presented in Table 2 and Table 3, Figure.

Table 2. Severity of discomfort in the lower extremities


VAD group (n=41)

Compression group (n=19)


Legs discomfort at baseline, VAS, mm




Legs discomfort at visit 3, VAS, mm







Mean decrease, before and after treatment

–20 (↓38%)

–7 (↓14%)


Table 3. QoL dynamics


VAD group (n=41)

Compression grou (n=19)


Global score of CIVIQ-20 at baseline




Global score of CIVIQ-20 at visit 3







Mean decrease, before and after treatment

+14 (↑ 22%)

+5 (↑ 5%)


Rates of symptoms of CVD (within-group comparison before and after the study).

32 (78%) patients of the VAD group were adherent with treatment which was confirmed by diaries analysis. Other patients reported missing several medication doses (from 1 to 11). The reason for missing was related to forgetfulness.

Only 5 (26.4%) patients who was prescribed with compression reported compliance with the treatment. Other did not use compression regularly or did not use it at all during in a peak of a hot weather in June—August.

No adverse events related to VAD or compression were registered.


A multicenter prospective study was conducted to compare the effectiveness of VAD therapy alone and compression therapy in symptomatic C1, C2 and C3 patient during the warm season. The background of the study is based on the practical observations that in the summer time patients often refuse to wear compression stockings or poorly follow recommendations for its use. We assumed that VAD therapy alone may be an effective alternative treatment in this period of the year.

We confirmed that medical treatment leads to significant improvement of venous symptoms and QoL in symptomatic patients during warm weather period of the year. Those who used VAD containing micronized diosmin 900 mg and hesperidin 100 mg (Angiorus) reported decrease in rates of venous symptoms and its severity asa well as increase of QoL global score. The same results were confirmed for compression group patients but the effect sizes were significantly smaller. Mean decrease of legs discomfort was 38 and 14% in a VAD and compression groups, resp. (p<0.001). Mean increase in QoL global score was 22 and 5% in a VAD and compression groups, resp. (p<0.001). The rate of every symptom significantly dropped in a VAD group while remained the same in the compression group. Our data are in concordance with the results of other researchers, who showed that VADs significantly reduces the frequency and severity of venous symptoms and improves QoL [11—13]

The data obtained during the follow-up of compression group patients should be interpreted taking into account that compression is considered the basic treatment for CVD. Compression has to be recommended to the majority of patients [1, 14]. Effect of compression was confirmed in uncomplicated varicose veins [15]. Orhurhu et al. reported reduction of venous pain under regular compression treatment [16]. Blazek et al. demonstrated 12% reduction in venous pain and heaviness [17]. At the same time, the effectiveness of compression can be significantly affected by poor patients’ adherence to prescriptions. In the PRIMER study 69% of patients did not follow physicians’ recommendation of what kind of compression had to be purchased 69% [6]. In a systematic review of 34 studies Kankam et al. showed that 74 and 63.5% of patients who participated in randomized and non-randomized trials, respectively, demonstrated good adherence [18]. In our study only 26.4% of patients whom compression was prescribed complied with the recommendations. We believe, that such a difference may be explained not only by the most often mentioned reasons (cost, difficulties in donning and doffing, discomfort etc.). In our opinion, warm weather played an important role in poor patients’ adherence in our study. In available literature we found only one similar data obtained in Brazil which is a country with a hot climate. It has been demonstrated that hot outside conditions led to refusal from wearing of compression in 29% of cases [19]. It should be mentioned that despite poor adherence to compression our patients demonstrated significant improvement in limb status QoL. This may be related to decrease in a workload and to increase in physical activity in the summer time. Moreover, compression group patients spent their holidays actively more often than in the VAD group.

Our study showed that VAD therapy alone is an alternative to compression treatment in hot weather season. Therapy with Angiorus (micronized diosmin/hesperidin) is associated with reduction in the rates of venous symptoms. It also leads to decrease in legs discomfort related to symptoms and to increase in QoL.


Limitations of our study include non-randomized design, different sample sizes which might led to a heterogeneity of the data. Patients in the compression group before the start of the study had a higher quality of life. They also had less venous edema, which could affect the severity of the effect obtained.


The adherence of C1S—C3S patients to compression therapy is very low in the warm weather season. Most of them do not use the recommended compression stockings at all or use compression irregularly. Venoactive drug therapy alone leads to significant decrease in the frequency and severity of venous symptoms and to improvement in the quality of life.

Author contributions:

The concept and design of the study — I.A. Zolotukhin, Yu.M. Stoyko, I.A. Suchkov

Collection and processing of material — O.V. Golovanova, O.I. Efremova, A.N. Kuznetsov, A.V. Tsyplyashchuk, A.A. Kamaev

Statistical data processing — O.V. Golovanova, O.I. Efremova, A.V. Tsyplyashchuk, A.A. Kamaev

Text writing — O.V. Golovanova, O.I. Efremova

Editing — I.A. Zolotukhin, Yu.M. Stoyko, I.A. Suchkov

Conflict of interest. The study was supported by the Binnopharm Group LLC. The Binnopharm Group LLC did not influence collection and analysis of data, as well as preparation of material for publication.

Email Confirmation

An email was sent to with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.