Specificities of the treatment of chronic venous diseases in Russia: preliminary results of the VEIN Act Program



by V. Bogachev, O. Golovanova,
A. Kuznet sov, P. Er shov, Russia

Vadim BOGACHEV, MD, PhD
Olga GOLOVANOVA, MD, PhD
Alexey KUZNETSOV, MD, PhD
Pavel ERSHOV, MD
Pirogov Russian National Research
Medical University (RNRMU)
Moscow, RUSSIA

The VEIN Act Program is an international study aimed at investigating the use of nonoperative treatments for chronic venous disease (CVD), assessing their efficacy and safety, and monitoring patient compliance. The Russian arm of the study revealed that venoactive drugs (VADs) are highly popular, both among physicians and patients, and that this is a factor that explains the high adherence to VAD treatment by Russian patients. The advice on lifestyle modifications was followed by more than 80% of patients, but often incompletely. Compliance with compression therapy was quite low and characterized by a reduction in the class of compression stockings and their irregular use in more than 30% of patients. The benefits of nonoperative CVD treatment in Russia were proven by the high level of patient satisfaction with treatment and also by a statistically significant decrease in the severity of CVD symptoms in the vast majority of patients.

Medicographia. 2016;38:181-186 (see French abstract on page 186)

Nonoperative treatments have undeniable benefits in the treatment of chronic venous disease (CVD) of the lower extremities. On the one hand, this is due to the epidemiology of CVD and the predominance of symptomatic forms that do not require surgical treatment.1,2 On the other hand, contemporary phlebology has extended the indications for nonoperative therapy in patients at high risk for CVD (long periods of time spent in the standing or sitting position, use of contraceptive hormones, hot weather, etc…) or undergoing interventional procedures (thermal ablation, sclerotherapy, phlebectomy, etc).3-5

Nonoperative treatment requirements, and compliance with such treatments, are determined by factors that are difficult to modify. This is why many epidemiological and clinical studies are designed to assess the various techniques of nonsurgical treatment of CVD. The VEIN Act Program, which was initiated by the European Venous Forum, is such a study. Its aim was to study the use of nonoperative CVD treatments, assess their efficacy and safety, and monitor patient compliance. This article presents the preliminary results of the Russian arm of this large-scale international project.

Methods

A total of 82 physicians from various regions of the Russian Federation participated in the VEIN Act Program and enrolled 1607 patients (325 males, 1282 females) aged between 18 and 89 years (mean age: 45.7 ± 14.1 years). The distribution of patients according to age is presented in Table I (page 182).

Patients were screened using the following inclusion criteria: confirmed primary CVD, presence of CVD-specific symptoms, and absence of any condition that could affect the study results. At the first visit (V0)—which sometimes coincided with the screening visit—patients were prescribed nonoperative treatments for their CVD. At the follow-up visit (V1), the physicians assessed the effects of the prescribed treatment and compliance with the treatment regimen. A 10-point visual analog scale (VAS) was used to assess symptom intensity.

Treatment outcomes were assessed after 60 to 90 days. The mean follow-up period was 87.2 ± 22.1 days. A total of 18 patients (1.1%) did not show up for the final visit (V1), and were therefore excluded from the analysis. Statistical analyses were performed by an independent expert using parametric and nonparametric methods.

Results and discussion

Patient characteristics are known to play an important role in the development and progression of CVD. The mean body mass index (BMI) of the patients included in the study was 26.0 ± 5.0 kg/m2, and 53.2% of them were either overweight or obese (BMI ≥25.0 kg/m2).

CVD symptoms at inclusion
The study included 1607 patients with various CVD-specific symptoms or signs of CVD at V0 (Tables II and III). Among them, 626 (39%) patients had already consulted a doctor for their leg problems, and 494 (31%) patients had already been treated for venous leg problems prior to inclusion in the study.

At baseline (V0), the severity of CVD symptoms was assessed using a 10-point VAS scale. The most distressing symptoms for patients were “leg heaviness,” “leg pain,” and “sensation of swelling” (Table IV). Symptom intensity was maximal at the end of the day in 87.2% of patients, after prolonged standing in 58.3% of patients, and/or during the night in 18.2% of patients. CVD-specific symptoms occurred regularly in 55.9% of patients, occasionally or rarely in 39.5% of patients, or persisted all day and night long in 3.6% of patients.

Nonoperative treatments prescribed
The study protocol specified that after assessing the phlebological status of their patients, doctors had to determine whether any treatment was needed. In 74.2% of cases a treatment was deemed necessary. Nonoperative therapy was prescribed in 65.2% of patients, surgery in 0.4% of patients, and a combination of these approaches in 33% of patients. Table V shows a breakdown of the nonoperative treatments prescribed. The term “other” in the table corresponds to those isolated cases where the use of various topical agents (ointments, gels, wound dressings) and/or pneumatic compression was recommended. Although many studies have found high rates of topical agent use in CVD patients, this was not the case in this study.

Table I. Patient distribution according to age.

Table II. Prevalence of chronic venous disease–related
complaints at V0.

Table III. Signs of chronic venous disease at V0.

Table IV. Severity scores of the main symptoms of chronic
venous disease assessed with a visual analogue scale (VAS) at
baseline (V0).

Lifestyle advice
The recent updates of the international and Russian guidelines for the clinical treatment of CVD have put emphasis on lifestyle recommendations to eliminate the risk factors that are known to contribute to the development of CVD.4-6 Table VI lists the lifestyle recommendations given to patients in the VEIN Act program.

Venoactive drugs
In our study, venoactive drugs (VADs) were prescribed to 1554 patients, but they were actually used by 1590 patients. It is interesting to note that a number of VADs that are widely used in clinical practice outside of Russia (ie, oxerutin, troxerutin, escin, proanthocyanidins, calcium dobesilate, etc) were not prescribed in this study.7,8 Micronized purified flavonoid fraction (MPFF) (brand name Detralex in Russia) was the most commonly prescribed VAD; it was prescribed in 93.9% of cases (Table VII). The international nonproprietary name (INN) of Detralex (ie, MPFF) seems to have confused many physicians, who either checked simultaneously the items “MPFF” and “Diosmin” or did not give any answer. Therefore, it is likely that the physicians who checked the “Diosmin” box also meant “MPFF” (Detralex).

The efficacy and safety of VADs depend on the dosage and duration of treatment, which are themselves determined by the choice of drug and the CVD class. The vast majority of patients took the standard daily dose of Detralex (1000 mg twice a day) (Table VIII). However, it should be noted that all patients who took 3 or 4 tablets of Detralex a day, as well as 10 of the 18 patients who took it once a day, had also been taking Detralex without a prescription. The reason for this is unclear, as the doctors involved in the study are highly qualified phlebologists who know firsthand how to prescribe the different VADs. Perhaps this was due to negligence in completing the questionnaires or to the use of certain “proprietary” regimens of VAD treatment. In addition, the only patient who had an adverse event during the study was a patient who had been taking 4 tablets of Detralex per day.

The optimal duration of VAD treatment in the initial stages of CVD is 8 weeks or more. In patients with advanced CVD— ie, with chronic venous edema or trophic skin lesions—VAD treatment can be prescribed for longer periods. However, in about one-third of patients (31.9%), VADs were administered for a period of 8 weeks or less, despite the fact that there is a direct correlation between the duration of VAD treatment and the duration of symptom remission.

Table V. Nonoperative treatment prescribed at V0.

Table VI. Lifestyle advice given to patients at V0.

Table VII. Venoactive drugs prescribed to the patients.

Table VIII. Prescribed dosage of venoactive drugs (number of
tablets per day).

Compression therapy
Compression therapy is a key component of noninterventional treatment for CVD. It is categorized according to the level of pressure applied at the ankle and the method of compression used (compression bandages or elastic graduated compression hosiery). For patients with CVD, optimal compression pressure at the ankle should be within the range of 20-30 mm Hg. The grade of compression can be reduced in early disease or increased in advanced disease. In our study, the appropriate grade of compression therapy was prescribed in 90.5% of patients. In 92.4% of cases, preference was given to compression hosiery. According to our data, 35 (2.2%) patients were prescribed both compression bandages and hosiery, but the reason for this is unclear. Perhaps the physicians felt that it was preferable to use compression bandages in the first stages of treatment in case of severe CVD (ie, chronic edema, trophic skin lesions). Another likely explanation is that the choice of compression method was left to the patients’ discretion. Detailed analysis of the type of compression prescribed showed that the use of compression therapy in Russia differs from that of the rest of the world. None of the physicians prescribed rigid bandages—though they are more effective—and in 3.4% of cases bandages with moderate or high stretchability were chosen. The most frequently recommended compression garments were stockings and tights (prescribed to 74.9% of patients), which are expensive and difficult to put on. Below-knee compression socks/stockings, which are more user-friendly and cost-effective, were prescribed to only 14.5% of patients. It is interesting to note that in other countries, the ratio of prescription of compression socks to compression stockings/tights is reversed, and this appears to be for mostly pragmatic reasons, rather than financial ones. The main goal of compression therapy in CVD is to improve calf-muscle pump function, which can be achieved equally well using medical compression stockings/tights and below-knee stockings. Since the latter are easier to put on and more comfortable to wear at any time of the year for both males and females, compliance with compression therapy with knee socks is expected to be higher. In addition, the cost of compression hosiery is an important issue, and below-knee stockings/socks are definitely more cost effective.9

Treatment compliance
♦ Lifestyle recommendations

One of the important goals of the VEIN Act Program was to evaluate treatment compliance. Life-style recommendations were followed by 1321 (82.2%) patients. Those who were not compliant gave the following reasons: lack of time, technical and organizational difficulties, and poor efficacy.

Figure 1. Mean severity scores for the main symptoms of chronic venous
disease before (V0) and after (V1) nonoperative treatment.

Venoactive drugs
In the study population, 93.7% of patients reported taking the VAD they were prescribed, and 87.4% of patients confirmed that they were compliant with the dosage regimen. However, more than one-third of patients followed their VAD treatment for less than 8 weeks, and 11.3% of patients reduced the duration of treatment of their own accord when the drug was prescribed for 9 weeks or more.

Figure 2. Percentage of patients affected by chronic venous disease–
specific symptoms before (V0) and after (V1) nonoperative
treatment.

Compression therapy
The recommended compression hosiery was purchased by 78.4% of patients. There was also a trend—though it was not significant—for under- or overestimation of the recommended class of compression by some patients. To achieve a therapeutic effect, compression hosiery should be worn for the entire time spent in an upright position. This recommendation was followed by 67.6% of patients, albeit with small variations.

Treatment outcomes
♦ Venoactive drugs

Following VAD treatment, 92.3% of patients experienced relief of their CVD-specific symptoms, and 67.2% of patients had a remission period of 3 weeks or more. In total, 8.8% of patients showed low compliance with VAD treatment due to various reasons.

Compression therapy
Relief from CVD symptoms was reported by 68.8% of patients who used compression therapy. Symptom relief lasting 3 weeks or more was reported by 62.4% of patients. Low compliance with compression therapy was recorded in 43.1% of patients.

Overall efficacy and patient satisfaction
Overall, the use of nonoperative treatment resulted in a statistically significant (P<0.00001) reduction in the severity of the main symptoms of CVD (Figure 1). There was also a statistically significant reduction in the number of patients experiencing symptoms (Figure 2). In addition, there was a statistically significant (P<0.00001) reduction in the frequency of CVD symptoms following completion of the treatment course (Figure 3).

Figure 3. Frequency of chronic venous disease–specific symptoms before
(V0) and after (V1) nonoperative treatment.

The vast majority (95%) of patients were satisfied with the treatment outcomes. Only 4% of patients rated their treatment as having failed or as having low efficacy. In 1% of cases no data were available. Although the VEIN Act Program was not designed to assess tolerability, 1 patient (out of 1607 patients) reported an adverse reaction in the form of skin rashes and itching in the upper and lower limbs three days after starting MPFF treatment at a dose of 4 tablets daily. This was twice the recommended dose and was, therefore, likely to have caused the adverse event.

Conclusion

In summary, the preliminary results of the Russian arm of the VEIN Act Program have highlighted a number of specificities regarding nonoperative treatment for CVD in Russia. First of all, VADs are extremely popular with both physicians and patients, and this explains the high adherence of Russian patients to VAD treatment. However, one in three patients does not follow the treatment regimen properly, and this is most often manifested by a reduction in treatment duration. Second, we were surprised to find that lifestyle recommendations were followed by more than 80% of patients, although often incompletely. Third, we found that compliance with compression therapy was low (ie, use of a lower class of compression and/or irregular use in more than 30% of patients), which is a shame given its effectiveness. Obviously, increasing the duration of treatment would lower the compliance even further. Nevertheless, the VEIN Act program has objectively proven the usefulness of nonoperative therapy in reducing the severity of CVD symptoms in the vast majority of patients and this resulted in high rates of patient satisfaction.

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Keywords: chronic venous disease; compression therapy; micronized purified flavonoid fraction; venoactive drug