To systematically review the evidence regarding long-term prophylaxis in the prevention or reduction of attacks in hereditary angio-oedema (HAE).
Systematic review and meta-analysis.
Electronic databases were searched up to April 2011. Two reviewers selected the studies and extracted the study data, patient characteristics and outcomes of interest.
Eligibility criteria for selected studies
Controlled trials for HAE prophylaxis.
7 studies were included, for a total of 73 patients and 587 HAE attacks. Due to the paucity of studies, a meta-analysis was not possible. Since two studies did not report the number of HAE attacks, five studies (52 patients) were finally included in the summary analysis. Four classes of drugs with at least one controlled trial have been proposed for HAE prophylaxis. All those drugs, except heparin, were found to be more effective than placebo. In the absence of direct comparisons, the relative efficacies of these drugs were determined by calculating a RR of attacks (drug vs placebo). The results were as follows: danazol (RR=0.023, 95% CI 0.003 to 0.162), methyltestosterone (RR=0.054, 95% CI 0.013 to 0.163), ɛ-aminocaproic acid (RR=0.095, 95% CI 0.025 to 0.356), tranexamic acid (RR=0.308, 95% CI 0.195 to 0.479) and C1-INH 0.491 (95% CI 0.395 to 0.607).
Few trials have evaluated the benefits of HAE prophylaxis, and all drugs but heparin seem to be effective in this setting. Since there are no direct comparisons of HAE drugs, it was not possible to draw definitive conclusions on the most effective one. Thus, to accumulate evidence for HAE prophylaxis, further studies are needed that consider the dose–efficacy relationship and include a head-to-head comparison between drugs, with the active group, rather than placebo, as the control.
To find evidence regarding long-term prophylaxis in the prevention or reduction of attacks in HAE.
Four classes of drugs have been proposed for HAE prophylaxis: androgen derivatives, antifibrinolytics, C1-inhibitor and heparin.
All, except heparin, have been shown to be more effective than placebo.
To accumulate evidence supporting HAE prophylaxis, further studies, including head-to-head comparisons between drugs, are needed, with the active group rather than placebo as the control.
Strengths and limitations of this study
This is the first systematic review on this topic.
Only seven studies were retrieved, for a total of 73 patients and 587 HAE attacks; there were no direct comparisons between drugs.
It was not possible to draw definitive conclusions on the most effective drug.