Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II) - A randomized,double-blind, placebo-controlled trial
H. Kiesewetter et al., Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II) - A randomized,double-blind, placebo-controlled trial, ARZNEI-FOR, 50(2), 2000, pp. 109-117
Red vine leaf extract (RVLE) is a herbal medicine containing several flavon
oids, with quercetin-3-O-beta-glucuronide and isoquercitrin (quercetin-3-O-
beta-glycoside) as the main components.
Objective - To assess the efficacy and safety of once daily doses of 360 an
d 720 mg RVLE (pharmaceutical extract code AS 195; Antistax(R) Venenkapseln
) compared to placebo in patients with stage I and incipient stage II chron
ic venous insufficiency (CVI).
Design - A 12-week, randomized, double-blind, placebo-controlled, parallel-
group, multi-center study.
Patients - Male and female outpatients aged 25 to 75 years with stage I to
stage II CVI (i.e. without extensive trophic changes), not having any other
significant medical conditions and not treated with compression stockings,
diuretics or other drugs affecting fluid balance.
Intervention - Patients were randomly assigned to a double-blind treatment
with placebo, 360 mg AS 195 or 720 mg AS 195 once daily for 12 weeks, prece
ded and followed by a single-blind 2-week placebo treatment for baseline ru
n-in and end-of-trial washout, respectively. Study criteria were evaluated
at baseline, after 6 and 12 weeks of treatment and 2 weeks after discontinu
ation of treatment.
Results - Of the 260 patients enrolled and randomized, 219 completed the st
udy in accordance with the protocol. In the intention-to-treat analysis (N
= 257), the mean (+/- SD) lower leg volume (measured by water displacement
plethysmography) of the patients treated with placebo (N = 87) increased by
15.2 +/- 90.1 g (displaced water mass) and by 33.7 +/- 96.1 g after 6 and
12 weeks compared to baseline. In contrast, for patients treated with AS 19
5, lower leg volume decreased, and after 12 weeks of treatment, the differe
nce in mean lower leg volume between the active treatment groups and the pl
acebo group was -75.9 g (95 % CI: -106.1 to -45.8 g) and -99.9 g (95 % CI:
-130.3 to -69.6 g) for the group treated with 360-mg AS 195 (N = 86) and 72
0-mg AS 195 (N = 84), respectively. The changes in calf circumference showe
d a similar pattern: in patients treated with AS 195, both the higher dose
(720 mg) and, albeit to a lesser extent, the lower dose (360 mg) resulted i
n a clear reduction in circumference over time, whereas, circumferences rem
ained largely unchanged in patients treated with the placebo (95 % CI of th
e estimated treatment effects vs. placebo after 12 weeks: -1.40 to -0.56 cm
and -1.73 to -0.88 cm for 360 and 720 mg AS 195, respectively). These diff
erences were statistically significant (p < 0.001). The reductions in ankle
circumference were qualitatively similar but quantitatively less marked. S
ubjectively there was an improvement in key CVI symptoms (VAS) at 6 weeks w
ith all treatments, but a further improvement at week 12 was seen only in t
he active treatment groups; at 12 weeks, the changes compared to baseline w
ere significantly greater (p < 0.001) in both active treatment groups than
in the placebo group. The treatments were well tolerated; Adverse events we
re rare and usually mild. Two adverse events (AEs) during treatment with th
e placebo led to hospitalization and were hence labeled as 'serious'. Three
further patients were withdrawn because of AEs which occurred during treat
ment with the placebo.
Conclusion - Once-daily doses of 360 and 720 mg AS 195 were confirmed to be
safe and effective in the treatment of mild CVI, reducing significantly lo
wer leg edema and circumference whilst improving key CVI-related symptoms t
o a clinically relevant extent. The edema reduction is at least equivalent
to that reported for compression stockings and/or other edema-reducing agen
ts. The higher dose was as well tolerated as the lower dose but resulted in
a slightly greater and more sustained improvement.