HR (Venoruton1000,Paroven,0-[beta-hydroxyethyl]-rutosides) vs. Daflon 500 in Chronic Venous Disease and Microangiopathy: An Independent Prospective,Controlled,Randomized Trial
Free accessResearch articleFirst published online September, 2002
HR (Venoruton1000,Paroven,0-[beta-hydroxyethyl]-rutosides) vs. Daflon 500 in Chronic Venous Disease and Microangiopathy: An Independent Prospective,Controlled,Randomized Trial
Objectives: The aim of this study was to demonstrate whether and how HR (Venoruton1000, Paroven, 0-[beta-hydroxyethyl]-rutosides) and Daflon (diosmin, 500 mg) were comparatively effective in improving the microcirculation in venous hypertension and microangiopathy.
Methods: A group of 90 patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a Venoruton and a Daflon (DF) group: patients in the Venoruton group received oral HR (2 g/day for 8 weeks); those in the Daflon group received three 500-mg tablets daily every 8 hours. The two groups were comparable for age and sex distribution. The mean age was 41 years (SD ± 11) in the Venoruton group (46 patients) and 41.3 (SD ± 12) in the DF group (44 patients).
Results: There were no differences in microcirculatory parameters between the Venoruton and DF treatment groups at inclusion. There was no significant change between inclusion and measurements at 8 weeks in the DF group. In comparison, a significant decrease (P < .05) in RF (resting skin flux) and RAS (rate of ankle swelling) was observed in the Venoruton group (P < .00 1). The decrease in capillary filtration was associated with improvement in signs and symptoms (measured by an analogue scale line) (P < .05). Symptomatic improvement was clinically and statistically significant and important only in the Venoruton group. No side effects and no drop-outs were observed.
Conclusion: Venous microangiopathy was improved by the treatment with Venoruton. The comparison with Daflon indicates that HR is comparatively more effective both on microcirculatory parameters and on signs and symptoms.
1. Beckers C, Zijilstra JA. New aspects of the pathogenesis of CVI and the site of action of Venoruton®. Phlebology Digest14:8-11, 2001
2.
2. Belcaro G, Rulo A, Candiani C. Evaluation of the microcirculatory effects of Venoruton in patients with chronic venous hypertension with laser Doppler flowmetry, transcutaneous P02 and PCO2 measurements, leg volumetry and ambulatory venous pressure measurements. Phlebology4:23-26, 1989
3.
3. Belcaro G, Nicolaides AN, Stansby G (eds). The Venous Clinic. Imperial College Press, London, 1999
4.
4. De Sanctis MT, Cesarone MR, Incandela L, Belcaro G, Acerbi G. Methods of evaluation and quantification of microangiopathy in high perfusion microangiopathy (Chronic venous insufficiency and diabetic microangiopathy). J Cardiovasc Pharmacol Therap7 [suppl I]:S3-S5, 2002
5.
5. Belcaro G, Nicolaides AN (eds). Noninvasive Investigations in Vascular Disease. Imperial College Press, London, 2001
6.
6. Almond NE, et al. A laser Doppler blood flowmeter used to detect thermal entrainment in normal persons and patients with Raynaud's phenomenon. In: Spence VA, Sheldon CD (eds.) Practical Aspects of Skin Blood Flow Measurement. Biological Engineering Society, London, 1985
7.
7. Anning ST. The cause and treatment of leg ulcers. Lancetii:789-791, 1952
8.
8. Anning ST. Leg Ulcers. Their Causes and Treatment. J & A Churchill Ltd, London, 1954
9.
9. Anning ST. The historical aspect. In Dodd H, Cockett FB (eds). The Pathology and Surgery of the Veins of the Lower Limb. Churchill-Livingstone, Edinburgh, 1976
10.
10. Belcaro G. The role of transcutaneous PCO2 measurements in association with laser Doppler flowmetry in venous hypertension. Phlebology3:189-193, 1988
11.
11. Belcaro G, Grigg M, Rulo A, Nicolaides AN. Blood flow in the perimalleolar skin in relation to posture in patients with venous hypertension. Ann Vasc Surg1:5-8, 1989
12.
12. Belcaro G, Christopoulos D, Nicolaides AN. Skin flow and swelling in postphlebitic limbs. Vasa18:136-138, 1989
13.
13. Belcaro G, Nicolaides AN, Volteas N, Leon M. Skin flow, the venoarteriolar response and capillary filtration in diabetics. A three-year follow-up study. Angiology43:490-494, 1992
14.
14. Belcaro G, Bollinger A, Hoffman U, Nicolaides AN (eds). Laser Doppler Flowmetry. Med-Orion, London, 1994
15.
15. Bergan JJ, Schmid-Schonbein GW, Takase S. Therapeutic approach to chronic venous insufficiency and its complications: Place of Daflon 500 mg. Angiology52 [suppl 1]:S43-S45, 2001
16.
16. Bollinger A, Jager K, Geser A, Sgier F, Seglis J. Transcapillary and interstitial diffusion of Na-Fluorescein in chronic venous insufficiency with white atrophy. Int J Microcirc1:5-8, 1982
17.
17. Fagrell B. Local microcirculation in chronic venous incompetence and leg ulcers. Vasc Surg13: 217-219, 1979
18.
18. Fagrell B. Microcirculatory disturbances–the final cause for venous leg ulcers?Vasa11:101-103, 1982
19.
19. Fagrell B. Problems using laser Doppler flowmetry on the skin in clinical practice. In: Belcaro G, Hoffman U, Nicolaides AN, Bollinger A (eds). Laser Doppler. Med Orion, London, pp. 49-53, 1994
20.
20. Franzeck U, Bollinger A, Huch R, Huch A. Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous incompetence. Circulation70:806-809, 1984
21.
21. Hendriksen O. Local reflex in microcirculation in human subcutaneous tissue. Acta Physiol Scand97:446-449, 1976
22.
22. Rayman G, Hassan A, Tooke JE. Blood flow in the skin of the foot related to posture in patients with diabetes mellitus. BMJ292:87-91, 1986
23.
23. Thulesius O. Capillary filtration under normal and pathological conditions. Angiologia10:198-201, 1973
24.
24. Cesarone MR, Ricci A, Belcaro G, Pomante P, Candiani C, Leon M, Nicolaides AN. Acute effect of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose-comparison study). Vasa21:76-79, 1992
25.
25. Belcaro G, Errichi BM. Evaluation of capillary permeability in patients with venous hypertension treated with Venoruton by the vacuum suction chamber (VSC) device. Phlebologie41:847-849, 1988
26.
26. Incandela L, Belcaro G, Renton S, et al. HR (Paroven,Venoruton; 0-[beta-hydroxyethyl]-rutosides) in venous hypertensive microangiopathy: A prospective, placebo-controlled, randomized trial. J Cardiovasc Pharmacol Therap7: [suppl I]:S7-S10, 2002
27.
27. Incandela L, Cesarone MR, Belcaro G, Dugall M, Acerbi G. Treatment of diabetic microangiopathy and edema with HR (Paroven,Venoruton; 0-[beta-hydroxyethyl]-rutosides): a prospective, placebo-controlled, randomized study. J Cardiovasc Pharmacol Therap7 [suppl I]: Sl1-S13, 2002
28.
28. Cesarone MR, Belcaro G, Incandela L, et al. Flight microangiopathy in medium-to-long-distance flights: Prevention of edema and microcirculation alterations with HR (Paroven,Venoruton; 0-[beta-hydroxyethyl]-rutosides). J Cardiovasc Pharmacol Therap7 [suppl I]:S17-S19, 2002
29.
29. Cesarone MR, Incandela L, De Sanctis MT, et al. Treatment of edema and increased capillary filtration in venous hypertension with HR (Paroven,Venoruton; 0-[beta-hydroxyethyl]-rutosides): A clinical, prospective, placebo-controlled, randomized, dose-ranging trial. J Cardiovasc Pharmacol Therap7 [suppl I]:S21-S25, 2002
30.
30. Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Dugall M, Acerbi G. Variations in plasma free-radicals in patients with venous hypertension with HR (Paroven,Venoruton; 0-[beta-hydroxyethyl]-rutosides): A clinical, prospective, placebo-controlled, randomized trial. J Cardiovasc Pharmacol Therap7 [suppl I]:S25-S28, 2002
31.
31. Gamer RC, Garner JV, Gregory S, Whattam M, Calam A, Leong D. Comparison of the absorption of micronized (Daflon 500 mg) and nonmicronized 14C-diosmin tablets after oral administration to healthy volunteers by accelerator mass spectrometry and liquid scintillation counting. J Pharm Sci91(1):32-37, 2002
32.
32. Danielsson G, Jungbeck C, Peterson K, Norgren L. A randomized controlled trial of micronized purified flavonoid fraction vs placebo in patients with chronic venous disease. Eur J Vasc Endovasc Surg. 23(l):73-79, 2002
33.
33. Poynard T, Valterio C. Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. Vasa23:244-260, 1994
34.
34. Ekestrom S, Welti R. The affinity of hydroxyethyl-rutosides for the venous wall and its efficacy in preventing early occlusion of aorto-coronary vein bypass grafts. Phlebology5 [sSuppl 1]:41-48, 1990
35.
35. Nees S, Juchem G, Fink R, Abbogast R. Influence of polymorphonuclear leukocytes and platelets on the barrierfunction of cultured venular endothelial cells. Proceedings 6th World Congress for Microcirculation. Monduzzi, Bologna 1996, pp. 401-404
36.
36. Roland IH, Bougelet C, Ninane N, Arnaud T, Michiels C, Remacle J. Effect of hydroxyethylrutosides on hypoxialinduced neutrophil adherence to umbilical vein endothelium. Cardiovasc Drugs Ther12:375-381, 1998
