Therapeutic approach to chronic venous insufficiency - clinical benefits of red-vine-leaf-extract AS 195 (Antistax®).

Background: Chronic Venous Disorders or Diseases (CVD) of the lower extremities are a common finding affecting almost 90 % of an adult population. CVD includes varicose veins with a prevalence of approx. 25 %, overlapping with Chronic Venous Insufficiency (CVI) with a prevalence of approx. 17% in the adult population. CVI is characterized by venous pathology and objective signs like edema, skin changes or venous leg ulcers. Objective: To review and evaluate non-clinical and clinical data on a standardised herbal product containing flavonoids (AS195; Antistax®) and to put them into a perspective with the pathophysiology of CVD. Methods: Literature available on non-clinical pharmacology and clinical studies with AS195 in CVI of the lower extremities was reviewed and described. Conclusion: Antistax® is a well-described herbal product with standardised starting materials and manufacturing process. Its active ingredients accumulate in the venous intima, preserve the endothelial barrier function, and inhibit the inflammatory and prothrombotic cascade behind the progression of CVD. Its efficacy was analysed in adequately planned and executed clinical trials in patients with mild to moderately severe CVD (CEAP C1s to C4). AS195 showed a statistically significant and clinically relevant efficacy over placebo: in objective endpoints like volumetry of lower leg edema, but also in outcomes directly relevant for patients like tension and heaviness of the legs, tingling, and pain. Supportive studies confirmed and validated these results also for the broader population treated in daily practice. AS195 was well tolerated in studies and in everyday therapy. There are no known interactions with other medications. In the later stages, it can be used in combination with compression, complementing the beneficial haemodynamic effects of compression at a cellular level. AS195 is an addition to compression and closes a therapeutic gap especially in patients, who cannot use compression stockings, but still require CVD therapy.

Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study.

OBJECTIVES: The aim of this study was to investigate the effect of a red-vine-leaf extract (AS195, Antistax(®), Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany) on the volume of the leg and clinical symptoms in patients with chronic venous insufficiency (CVI). DESIGN, MATERIALS AND METHODS: A multicentre, randomised, double-blind and placebo-controlled study was carried out with 720 mg AS195 per day over 12 weeks in CVI patients (CEAP Grades 3-4a) and moderate-to-severe clinical symptoms. Efficacy endpoints were changes in limb volume determined by water displacement volumetry, clinical CVI symptoms assessed on a 10-cm visual analogue scale and global efficacy evaluations. RESULTS: The full-analysis set included 248 patients (placebo: n = 122; AS195: n = 126). After 12 weeks, AS195 significantly reduced lower limb volume by a mean of 19.9 standard error (SE) 8.9 ml over placebo (95% confidence interval (CI): -37.5, -2.3; p = 0.0268; analysis of covariance, ANCOVA). The standardised effect size of 0.28 for volume reduction indicates a clinically relevant effect. On Day 84, the symptom of 'pain in the legs' assessed by visual analogue scale decreased in the AS195 group compared with the placebo group: mean difference -6.6 SD 3.3 mm (95% CI: -13.1,-0.1; p = 0.047). Other symptoms showed no significant change. The tolerability of AS195 was similar to that of placebo. CONCLUSIONS: AS195 treatment for 84 days resulted in an approximately 20 ml reduction of limb volume in the active treatment group compared with the placebo group. Patients reported subjective improvement following treatment with AS195 compared with placebo. However, patients' overall rating of efficacy did not correlate well with measured reductions in limb volume. TRIAL REGISTRATION: ClinicalTrials.gov NCT00855179.

Rational therapy of chronic venous insufficiency--chances and limits of the therapeutic use of horse-chestnut seeds extract.

BACKGROUND AND METHODS: We report two clinical studies, one already published, performed in patients with early and advanced chronic venous insufficiency (CVI). In both, compression therapy and oral therapy with horse-chestnut seeds extracts (HCSE) were compared to placebo. RESULTS: The published study in early CVI (Grade I) showed HCSE and compression to be superior to placebo and to be equivalent to each other in reducing lower leg volume, a measure for oedema. In the study, in advanced CVI (Grade II and IIIa), compression appeared to be superior to placebo, whereas HCSE was not. HCSE fared better in Grade II than in Grade IIIa patients. These results are discussed in the light of data from an in vitro model, where HCSE has been able to close the intercellular gaps in the venular endothelium. Not fully specified factors lead to an opening of these gaps, resulting in oedema as well as in local coagulation and thrombosis. The subsequent inflammation keeps these gaps open and initiates and maintains a chronic disease process, which may be the starting point of CVI. CONCLUSION: Due to its ability to close the venular endothelial gaps, HCSE seems to be a suitable and protecting therapy during the early stages of CVI. In later more severe stages compression therapy is indicated. Taking into account the observed negative impact of compression on quality of life, pharmacological CVI therapy should start early to avoid progress and to spare patients compression therapy.

Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis.

OBJECTIVE: A double-blind, placebo-controlled dose-finding study was performed in 237 patients with predominantly unilateral knee osteoarthritis (OA) evaluating efficacy and safety of a new topical NSAID. DESIGN: The patients applied 3 g tid eltenac gel 0.1%, 0.3%, 1% or placebo gel over a period of 4 weeks. The patients were supplied with paracetamol tablets as an escape analgesic. Primary efficacy end-point was mean global pain in the week preceding the examinatio ns, evaluated on a visual analog scale (VAS). Secondary criteria were Lequesne's score ISK, Jezek score, muscle strength and dolorimeter measurements, walking time, clinical examination results of the knee joint and patient's and investigator's overall efficacy estimates. RESULTS: The graphical depiction of VAS and ISK suggested a dose-related efficacy, but the pre-planned statistical analysis did not show significant differences between treatments. In the patient subgroup with a higher degree of baseline severity of knee OA the ISK showed significant and relevant advantages of eltenac gel 1% to placebo at different examination times. Two patients each of the eltenac gel 1% group and the placebo group showed local intolerance reactions which subsided spontaneously. CONCLUSION: This study did not provide confirmatory proof of an efficacy of topical eltenac in patients with knee OA. Methodological pitfalls and possible responder subgroups are described. Despite the difficulties, dose-finding studies seem to be feasible even with topical NSAIDs.