Most medications used for long‐term prevention of hereditary angioedema (HAE) attacks, except for avoralstat, were effective in reducing the risk and/or incidence of HAE attacks, according to a new meta‐analysis published by the Cochrane Review.

Moreover, intravenous and subcutaneous forms of C1 esterase inhibitor (C1‐INH) and lanadelumab reduced breakthrough attack severity.

“It is possible that danazol, subcutaneous C1‐INH and recombinant human C1‐INH are more effective than berotralstat and lanadelumab in reducing the risk of breakthrough attacks, but the small number of studies and the small size of the studies means that the certainty of the evidence is low. This and the lack of head‐to‐head trials prevented us from drawing firm conclusions on the relative efficacy of the drugs,” the authors wrote.

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In addition, avoralstat, berotralstat, C1‐INH, and lanadelumab had a positive impact on patient quality of life. The last 3 were shown to decrease disability compared with placebo. Evidence suggests that all drugs were well tolerated, with similar frequency of adverse events, including serious adverse events, as placebo. There was no data available evaluating the impact of danazol on patient quality of life or its safety.

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The meta-analysis conducted by the authors included 15 studies with a total of 912 participants with type 1 or type 2 HAE. The studies investigated avoralstat, berotralstat, subcutaneous C1‐INH, plasma‐derived C1‐INH, nanofiltered C1‐INH, recombinant human C1‐INH, danazol, and lanadelumab as preventive strategies for HAE attacks. The authors did not find studies on the use of tranexamic acid and older drugs or studies enrolling patients with type 3 HAE.

The primary outcomes of the meta-analysis were HAE attacks (number of attacks per person, per population) and change in number of HAE attacks, mortality, and serious adverse events. Secondary outcomes included quality of life, severity of breakthrough attacks, disability, and adverse events.


Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022;11(11):CD013403. doi:10.1002/14651858.CD013403.pub2