However, experience withC1-esterase inhibitor in long-term prophylactic therapy is not as extensive as foracute treatment or short-term prophylaxis; long-term prophylaxis was not exploreduntil 1989 and efficacy in a controlled trial was not confirmed until 1996[49,91].Studies with earlier C1-esterase inhibitor formulations have shown a reduction inthe frequency of attacks in patients with HAE[92]. The gene discussed is C1S; the disease is hereditary angioedema.