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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by inadequate blood flow through the veins, usually in the lower limbs. It can result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Sufferers may also experience swelling and ulcers. Phlebotonics are a class of drugs that are often used to treat CVI. OBJECTIVES: To assess the efficacy of oral or topical phlebotonics. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group trials register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005), MEDLINE (January 1966 to April 2005), EMBASE (January 1980 to April 2005) and reference lists of articles. We also contacted pharmaceutical companies. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in CVI patients at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. The effects of treatment were estimated by relative risk (RR) or by standardised mean differences (SMD) by applying a random effects statistical model. Sensitivity analyses were also performed. MAIN RESULTS: Fifty-nine RCTs of oral phlebotonics were included, but only 44 trials involving 4413 participants contained quantifiable data for the efficacy analysis: 23 of rutosides, ten of hidrosmine and diosmine, six of calcium dobesilate, two of centella asiatica, one of french maritime pine bark extract, one of aminaftone and one of grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Outcomes included oedema, venous ulcers, trophic disorders, subjective symptoms (pain, cramps, restless legs, itching, heaviness, swelling and paraesthesias), global assessment measures and side effects. The results of many variables were heterogeneous. Phlebotonics showed some global benefit (i.e. oedema reduction) (relative risk 0.72, 95% confidence interval 0.65 to 0.81). The benefit for the remaining CVI signs and symptoms must be evaluated by phlebotonic group. There were no quantifiable data on quality of life. AUTHORS' CONCLUSIONS: There is not enough evidence to globally support the efficacy of phlebotonics for chronic venous insufficiency. There is a suggestion of some efficacy of phlebotonics on oedema but this is of uncertain clinical relevance. Due to the limitations of current evidence, there is a need for further randomised, controlled clinical trials with greater attention paid to methodological quality.[1]


  1. Phlebotonics for venous insufficiency. Martinez, M.J., Bonfill, X., Moreno, R.M., Vargas, E., Capellà, D. Cochrane database of systematic reviews (Online) (2005) [Pubmed]
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