Benzo-pyrones in the treatment of lymphoedema

Fifty clinical trials of 4 benzo-pyrones in the treatment of lymphoedema, by over 37 authors in 8 countries, are reviewed: 38 oral and 12 topical (11 and 6 of these, added to other therapies). Oral benzo-pyrones reduced oedema, symptoms (in almost all) and inflammation (SAI). These were significant and clinically important. There were no significant differences between arms and Grades 1 and 2 legs. Combining these 20 trials gave mean annual reductions of 55% of oedema (SE: 7.8%; 95% Confidence Interval: 40% to 71%) (p<0.001). Four trials of elephantitic legs gave 17% (4.8%; 7.6% to 27%), significantly less (p<0.01). Meta-analyses, tested by omitting non-double-blind or non-peer-reviewed trials, were robust. The greater the oedema, the greater the rate of reduction-lessening as time passed and the oedema reduced: annual reduction=37%x(79%) Period (p=0.01). Reductions varied with the molar dose (p=10(-8)): =0.10% (SE 0.013%) Dose (mg of coumarin or molar equivalent of other drugs). Topical coumarin also reduced oedema and symptoms. The results of some other therapies were improved by oral or topical benzo-pyrones 15% to 22% over a month and 0% to 78% over a year. These drugs are slow, but effective, cheap and convenient. Because of their slowness, compression garments are unnecessary. They were seldom used in trials. Side-effects are minimal. Only oral coumarin may cause idiosyncratic hepatitis (3 per 1,000). Topical coumarin does not, nor other benzo-pyrones.