The quality of evidence is downgraded by study limitations (unclear allocation concealment).
A Cochrane review on oral or topical phlebotonics in chronic venous insufficiency (CVI) included 66 studies and analysed data from 53 studies, with a total of 6 013 subjects. Phlebotonics represent a heterogeneous group of venoactive medications, mostly natural flavonoids extracted from plants and synthetic products with flavonoid-like properties. Of the trials included in the efficacy analysis, 28 were of rutosides, 10 of hidrosmine and diosmine, 9 of calcium dobesilate, 2 of centella asiatica, 2 of french maritime pine bark extract, 2 of aminaftone and 1 of grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.
Phlebotonics reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; 13 studies, n=1 245) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies, n=2 010) compared with placebo. There was no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; 6 studies, n=461). Phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. There was heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. Phlebotonics group had greater risk of adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.40; 34 studies, n=4 054). Gastrointestinal disorders were the most frequently reported adverse events.
Comment: Studies included in this review provided only short-term safety data; therefore, the middle- and long-term safety of phlebotonics could not be estimated.