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A Journal on Angiology

Official Journal of the International Union of Angiology, the International Union of Phlebology and the Central European Vascular Forum
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International Angiology 1999 March;18(1):31-41

language: English

Benzo-­pyrones in the treat­ment of lym­phoe­de­ma

Casley-Smith J. R. *

From the Lymphoedema Association of Australia (Henry Thomas Laboratory) University of Adelaide, Australia


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%×(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.

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