HR,0-(Beta-Hydroxyethyl)-Rutosides;(Venoruton®): Rapid Relief of Signs/Symptoms in Chronic Venous Insufficiency and Microangiopathy: A Prospective,Controlled Study

Abstract

The aim of this independent study was to demonstrate the rapidity of the clinical action of HR 0-(beta-hydroxyethyl)-rutosides, Venoruton^® (Novartis Consumer Health) in patients with chronic venous insufficiency (CVI). Two groups of patients with venous hypertension and microangiopathy were treated with HR (1 or 2 g/day, for 8 weeks). Twelve patients (age 56.4; range 44-66; M:F = 6:6) were included in group 1 (1 g/day) (moderate CVI and microangiopathy); 10 patients (age 57.4; range 42-67; M:F = 5:5) in group 2 (2 g/day) with more severe CVI and microangiopathy. Average ambulatory venous pressure (AVP) was 58.6 (range 50-65) with a refilling time (RT) shorter than 10 seconds. There were no significant differences in AVP and RT between the 2 groups, but the duration of the disease was longer in group 2: 3.5 years (SD 2.0) in group 1 and 6.4 years (SD 3.3) in group 2. All included subjects completed the study and no dropouts were observed. In both dose groups there was a progressive decrease in laser Doppler resting flux (RF), indicating improvement in microangiopathy and a significant decrease in capillary filtration (RAS) associated with a significant improvement in analogue scale line score (ASLS) and edema. Although the effect in the 2 g dose group was more rapid on the microcirculatory parameters with a significant effect on RF and RAS after 4 days (effect of 1 g per day after 8 days and 6 days, respectively), there was no difference in the time to onset of a significant clinical improvement (ie, the ASLS and the edema score): 4 days in both groups. Venous microangiopathy and edema were improved by the treatment with HR within a few days. The effects were visible with both dosages, in both severity groups.

References

Beckers C , Zijilstra JA : New aspects of the pathogenesis of CVI and the site of action of Venoruton®. Phlebology Digest 14:8-11, 2001.

Belcaro G , Rulo A , Candiani C : Evaluation of the microcirculatory effects of Venoruton® in patients with chronic venous hypertension with laser Doppler flowmetry, transcutaneous PO2 and PCO2 measurements, leg volumetry and ambulatory venous pressure measurements. Phlebology 4:23-26, 1989.

Cesarone MR , Ricci A , Belcaro G , et al : Acute effect of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose-comparison study). Vasa 21:76-79, 1992.

Belcaro G , Errichi BM : Evaluation of capillary permeability in patients with venous hypertension treated with Venoruton® by the vacuum suction chamber (VSC) device. Phlebologie 41:847-849, 1988.

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 Ther 7(suppl I):S7-S10, 2002.

Incandela L , Cesarone MR , Belcaro G , et al : Treatment of diabetic microangiopathy and edema with HR (Paroven, Venoruton®; 0(beta-hydroxyethyl-rutosides): A prospective, placebo-controlled, randomized study. J Cardiovasc Pharmacol Ther 7(suppl I):S11-S13; 2002.

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 Ther 7(suppl I):S17-S19; 2002.

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 Ther 7(suppl I):S21-S25, 2002.

Rehn D , Unkauf M , Klein P , et al : Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency. Arzneimittelforschung 46:483-487, 1996.

10.

De Sanctis MT , Cesarone MR , Incandela L , et al : Methods of evaluation and quantification of microangiopathy in high-perfusion microangiopathy (Chronic venous insufficiency and diabetic microangiopathy). J Cardiovasc Pharmacol Ther 7(suppl I):S3-S5, 2002.

11.

Belcaro G , Nicolaides AN (eds): Noninvasive Investigations in Vascular Disease. London: Imperial College press, 2001.

12.

Almond NE : A laser Doppler blood flowmeter used to detect thermal entrainment in normal persons and patients with Raynaud's phenomenon. In: Practical Aspects of Skin Blood Flow Measurement, ed by Spence VA , Sheldon CD. London: Biological Engineering Society, 1985.

13.

Anning ST : The cause and treatment of leg ulcers. Lancet ii:789-791, 1952.

14.

Anning ST : Leg Ulcers. Their Causes and Treatment. London: J & A Churchill Ltd, 1954.

15.

Anning ST : The historical aspect. In: The Pathology and Surgery of the Veins of the Lower Limb, ed by Dodd H , Cockett FB. Edinburgh: Churchill-Livingstone, 1976.

16.

Belcaro G : The role of transcutaneous PCO2 measurements in association with laser Doppler flowmetry in venous hypertension. Phlebology 3:189-193, 1988.

17.

Belcaro G , Grigg M , Rulo A , et al : Blood flow in the perimalleolar skin in relation to posture in patients with venous hypertension. Ann Vasc Surg 1:5-8, 1989.

18.

Belcaro G , Christopoulos D , Nicolaides AN : Skin flow and swelling in postphlebitic limbs. Vasa 18:136-138, 1989.

19.

Belcaro G , Nicolaides AN , Volteas N , et al : Skin flow, the venoarteriolar response and capillary filtration in diabetics. A three-year follow-up study. Angiology 43:490-494, 1992.

20.

Belcaro G , Bollinger A , Hoffman U , et al (eds): Laser Doppler Flowmetry. London: Med-Orion, 1994.

21.

Bergan JJ , Schmid-Schonbein GW , Takase S : Therapeutic approach to chronic venous insufficiency and its complications. Angiology 52(suppl 1):S43-S45, 2001.

22.

Belcaro G , Nicolaides AN , Stansby G (eds): The Venous Clinic. London: Imperial College Press, 1999.

23.

Bollinger A , Jager K , Geser A , et al : Transcapillary and interstitial diffusion of Na-Fluorescein in chronic venous insufficiency with white atrophy. Int J Microcirc I:5-8, 1982.

24.

Fagrell B : Local microcirculation in chronic venous incompetence and leg ulcers. Vasc Surg 13:217-219, 1979.

25.

Fagrell B : Microcirculatory disturbances—the final cause for venous leg ulcers? Vasa 11:101-103, 1982.

26.

Fagrell B : Problems using laser Doppler flowmetry on the skin in clinical practice. In: Laser Doppler, ed by Belcaro G , Hoffman U , Nicolaides AN , et al. London: Med Orion, pp 49-53, 1994.

27.

Franzeck U , Bollinger A , Huch R , et al : Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous incompetence. Circulation 70:806-809, 1984.

28.

Hendriksen O : Local reflex in microcirculation in human subcutaneous tissue. Acta Physiol Scand 97:446-449, 1976.

29.

Rayman G , Hassan A , Tooke JE : Blood flow in the skin of the foot related to posture in patients with diabetes mellitus. Br Med J 292:87-91, 1986.

30.

Thulesius O : Capillary filtration under normal and pathological conditions. Angiologia 10:198-201, 1973.

31.

Cesarone MR , Incandela L , De Sanctis MT , et al : 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 Ther 7(suppl I):S25-S28, 2002.

32.

Belcaro G , Cesarone MR , Bavera P , et al : HR (Venoruton® 1000, Paroven, 0-[beta-hydroxyethyl]-rutosides) vs Daflon 500 in chronic venous disease and microangiopathy: An independent prospective, controlled, randomized trial. J Cardiovasc Pharmacol Ther 7:139-145, 2002.

33.

Poynard T , Valterio C : Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. Vasa 23:244-260, 1994.

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. Phlebology 5(suppl 1):41-48, 1990.

35.

Roland IH , Bougelet C , Ninane N , et al : Effect of hydroxyethylrutosides on hypoxial-induced neutrophil adherence to umbilical vein endothelium. Cardiovasc Drugs Ther 12:375-381, 1998.