ACE INHIBITOR-INDUCED ANGIOEDEMA - INCIDENCE, PREVENTION AND MANAGEMENT

Available information from 1980 to 1997 on angiotensin converting enzy me (ACE) inhibitor-induced angioedema and its underlying mechanisms ar e summarised and discussed. The incidence of angioedema is low (0.1 to 0.2%) but can be considered as a potentially life-threatening adverse effect of ACE inhibitor therapy. This adverse effect of ACE inhibitor s, irrespective of the chemical structure, can occur early in treatmen t as well as after prolonged exposure for up to several years. The est imated incidence is quite underestimated. The actual incidence can be far higher because of poorly recognised presentation of angioedema as a consequence of its late onset in combination with usually long term therapy. Also, a spontaneous reporting bias can contribute to an actua l higher incidence of this phenomenon. The incidence can be even highe r (up to 3-fold) in certain risk groups, for instance Black Americans. Treatment includes immediate withdrawal of the ACE inhibitor and acut e symptomatic supportive therapy followed by immediate (and long term) alternative therapy with other classes of drugs to manage hypertensio n and/or heart failure. Preclinical and clinical studies for the eluci dation of the underlying mechanism(s) of ACE inhibitor-associated angi oedema have not generated definite conclusions. It is suggested that i mmunological processes and several mediator systems (bradykinin, hista mine, substance P and prostaglandins) are involved in the pathogenesis of angioedema. A great part of all reviewed reports suggest a relatio nship between ACE inhibitor-induced angioedema and increased levels of (tissue) bradykinin. However, no conclusive evidence of the role of b radykinin in angioedema has been found and an exclusive role of bradyk inin seems unlikely. So far, no clear-cut evidence for an immune-media ted pathogenesis has been found. In addition, ACE gene polymorphism an d some enzyme deficiencies are proposed to be involved in ACE inhibito r-induced angioedema. Progress in pharmacogenetic and molecular biolog ical research should throw more light on a possible genetic component in the pathogenesis of ACE inhibitor-associated angioedema.