In Belgium and Luxembourg, a study of the patients with chronic venous insufficiency (CVI) found that the most common symptom was heaviness in the legs, which occurred in 70% of patients, about 50% experiencing pain and 20% complaining of itching or paresthesia. Seventy-five percent of patients reported experiencing more than one symptom (
Most of VADs are natural flavonoids extracted from plants, and synthetic drugs with similar properties are also used Table 1. In the Anatomical Therapeutic Chemical (ATC) system, VADs are classified as vasoprotective agents (C05, vasoprotectives, C05C, capillary stabilizing agents) (ATC 2020) (
|Group||Substance||Origin||Recommendation grade (2018 UIP guideline)||Commercial products in Korea|
|Diosmin||Citrus spp.||1||조아디오스민(조아제약), 디오맥스(동아제약), 베노론(한올바이오파마), 치센(동국제약)|
|MPFF*||Rutaceae aurantiae||1||베니톨(광동제약), 플라벤정(태극제약), 프라린정(경남제약), 프라빈정(동성제약), 치벤정(영일제약)|
|Rutin and rutosides||Sophora japonica||1||-|
|HR*||Eucalyptus spp.||1||엘라스에이(조아제약), 케이나(삼진제약), 헤모케어(오스틴제약)|
|Ruscus extract||Butcher’s broom||1||-|
|Other plant extracts||Anthocyans||Bilberry||2C||타겐에프(국제약품)|
|Proanthocyanidins||Maritime pine, Vitis vinifera||2C||엔테론(한림제약)|
|Centella asiatica||Centella, Gotukola||-||센시아정(동국제약)|
|Synthetic product||Calcium dobesilate||Synthetic||2||독시움(일성신약)|
*MPFF: micronized purified flavonoid fraction, HR: 0-(b-Hydroxyethyl)-rutosides (troxerutin).
Most studies on VADs were conducted in patients with chronic venous insufficiency and were shown to be effective in reducing discomfort and swelling in the lower extremities. (
In the 2005 Cochrane Review, the efficacy of all VADs was analyzed and reported in 4413 patients included in 44 studies published up to 2005 (
Additionally, an analysis of the symptom effect of each drug type was conducted separately. Swelling, pain, and cramping were all improved in common, but for other symptoms, the effect was different for each drug. Unlike other medications, diosmin-based drugs could reduce heaviness (Standardized mean difference, SMD -0.69 [-1.02 to -0.36]) (
Micronized purified flavonoid fraction (MPFF) is a mixed drug containing 90% and 10% diosmin and hesperidin, respectively. An interesting study of the effects of MPFF in 2017 was conducted in Russia. Doppler ultrasound was performed in the morning and evening in 96 C1 patients, and vein size was measured. Transient venous reflux (TVR) was observed only in the evening in 55.2% of patients. MPFF (DaflonⓇ 1000 mg; Servier, Suresnes, France) was prescribed for 90 days. In 92.5% of patients, TVR disappeared, the diameter of the great saphenous vein (5.69 mm to 5.14 mm, p<0.01) was significantly decreased, and the quality of life was also improved (QoL score 42.03 to 30.10, p<0.01) (
Centella asiatica was extracted from gotu grass. In a systematic review of the literature conducted in 2013, eight studies were summarized, and most showed improvement in venous reflux, clinical manifestations of venous insufficiency, venous wall tone, venous hypertension, and microcirculation. In these studies, the total triperpenic fraction of centella asiatica (TTFCA) was used at 60 mg or 120 mg per day, and the duration of use was 4 to 8 weeks (
The 2008 European venous forum (EVF) guidelines evaluated the efficacy and safety of VADs (
The 2018 EVF guidelines’ approach to determining the magnitude of the effect of individual VADs on specific symptoms provided evidence on the appropriate choice of VADs (
The 2008 ACCP guidelines recommend the addition of MPFF, rutosides, and sulodexide to compression therapy for patients with persistent venous ulcers (Grade 2, level of evidence B) (
In 2011, CPG of the SVS and the AVF recommended the use of VADs (diosmin, hesperidin, rutosides, sulodexide, MPFF or horse chestnut seed extract [aescin]) in patients with pain and swelling due to chronic venous disease [Grade 2, level of evidence B]. To accelerate the healing of venous ulcers, it is recommended to use pentoxifylline or MPFF with compression treatment where possible [Grade 2, level of evidence B] (
European clinical practice guidelines (CPG of the ESVS, 2015) recommend that VADs be considered as a treatment option for swelling and pain caused by chronic venous disease [Class IIa, level of evidence A] (
In 2016, the Deutsche Dermatologische Gesellschaft specifically recommended the duration of use of VADs; when evaluating the clinical effect in daily life, 2∼4 weeks of continuous intake is necessary to fully exert their effect [Grade 1-C] (
TThe EVF guidelines recommended the following regar-ding the use of VADs. These drugs can be used as the primary treatment for symptoms and edema in all stages of chronic venous disease. In more advanced disease stages, VADs can be used in conjunction with stripping, endovenous thermal ablation, sclerotherapy, or compressive stocking, and can improve the effectiveness of compression. (13). Most VADs showed a common effect on swelling, pain, cramping, and heaviness. However, as analyzed and reported by the Cochrane Review in 2020 and the EVF Guidelines in 2018, VADs seem to differ in efficacy by ingredient, and improved clinical patterns were also varied (4,16). Therefore, it is necessary to use appropriate VADs according to the severity of the patient’s symptoms and stage of disease.
The same topic was presented at the 40th Conference of the Korean Society for Phlebology on April 18, 2021.
The author declares no potential conflict of interest.