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Page 10 of 13 Smetanina et al. Vessel Plus 2021;5:19 https://dx.doi.org/10.20517/2574-1209.2021.17

Calcium dobesilate Dioxybenzene derivative Doxium (calcium dobesylate) [Serbia, Russia], Evadol and Proxacin Reduces leg (o)edema; improves CVD symptoms. [47,48]
[A] (synthetic drug) [Peru], Danium [Czech Republic], Calcium dobesilate Galena
[Poland]

III. Other venoactive drugs
®
Sulodexide Porcine-derived extracts of Vessel [Italy], Aterina [Spain], Vessel Due F [Russia and all over the Reduces peripheral venous pressure, improves both objective [44,68-70]
intestinal mucosa (two world] and subjective CVD symptoms and QoL, improves ulcer
glycosaminoglycans: 80% of healing, prevents recurrent venous thromboembolism
fast-moving heparin and 20%
dermatan sulfate)
Gotu Kola (Centella Saponosides Madecassol [Greece, Portugal, Turkey], Centellase [Italy] Stimulates collagen production, reduces swelling and improves [71]
asiatica) circulation; is used to treat venous insufficiency and heal
wounds

§ [47]
Grade of Recommendations (according to Ramelet et al. ) depends on the conduction of the Randomized Controlled Trial (RCT): (a) RCT with large sample sizes, valid meta-analyses (Grade A); (b) RCT with
† ‡
small sample size (Grade B); and (c) other controlled trials, no RCTs (Grade C). Esculin is a coumarin glycoside from the leaves and bark of horse chestnut (glycone - glucose, aglycone - 6,7-dioxycoumarin).

Heptaminol hydrochloride tones up varicose veins and has a cardio-stimulating effect. Some venoconstrictor/venotonic only drugs [such as α-adrenergic agonists fentanyl (Ethylephrine; Actiq, Duragesic,
Sublimaze) and midodrine [Gutron; Orvaten, ProAmatine]; dihydrogenated ergot alkaloids (Dihydroergotoxin, Dihydroergotamine, Dihydroergocriptine, Vazobral)] were not included in this table due to their
*
irrelevance for CVD treatment. CVD: Chronic venous disease. QoL: quality of life. CVI: chronic venous insufficiency.

some miracle remedy will be invented, even if not universal, but which will really be able to help patients.

DECLARATIONS

Acknowledgments
The authors are grateful to the native English speakers Holly Jacob (Texas A&M University, USA) and Christine Tierney (Houston Community College, USA)

for grammar checking assistance and thorough text revision.

Authors’ contributions
Made substantial contributions to conception and design of the study: Smetanina MA, Shevela AI, Gavrilov KA, Filipenko ML

Performed literature analysis and writing the manuscript: Smetanina MA
Helped with data interpretation relating to clinical part: Shevela AI, Gavrilov KA
Helped with data acquisition, as well as provided administrative, technical, and material support: Filipenko ML

Availability of data and materials
Not applicable.