Vleeming W, van Amsterdam J G, Stricker B H, de Wildt D J
National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Drug Saf. 1998 Mar;18(3):171-88. doi: 10.2165/00002018-199818030-00003.
Available information from 1980 to 1997 on angiotensin converting enzyme (ACE) inhibitor-induced angioedema and its underlying mechanisms are 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 inhibitors, irrespective of the chemical structure, can occur early in treatment as well as after prolonged exposure for up to several years. The estimate 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 actual higher incidence of this phenomenon. The incidence can be even higher (up to 3-fold) in certain risk groups, for instance Black Americans. Treatment includes immediate withdrawal of the ACE inhibitor and acute symptomatic supportive therapy followed by immediate (and long term) alternative therapy with other classes of drugs to manage hypertension and/or heart failure. Preclinical and clinical studies for the elucidation of the underlying mechanism(s) of ACE inhibitor-associated angioedema have not generated definite conclusions. It is suggested that immunological processes and several mediator systems (bradykinin, histamine, substance P and prostaglandins) are involved in the pathogenesis of angioedema. A great part of all reviewed reports suggest a relationship between ACE inhibitor-induced angioedema and increased levels of (tissue) bradykinin. However, no conclusive evidence of the role of bradykinin in angioedema has been found and an exclusive role of bradykinin seems unlikely. So far, no clear-cut evidence for an immune-mediated pathogenesis has been found. In addition, ACE gene polymorphism and some enzyme deficiencies are proposed to be involved in ACE inhibitor-induced angioedema. Progress in pharmacogenetic and molecular biological research should throw more light on a possible genetic component in the pathogenesis of ACE inhibitor-associated angioedema.
总结并讨论了1980年至1997年期间有关血管紧张素转换酶（ACE）抑制剂诱发血管性水肿及其潜在机制的现有信息。血管性水肿的发生率较低（0.1%至0.2%），但可被视为ACE抑制剂治疗的一种潜在危及生命的不良反应。ACE抑制剂的这种不良反应，无论其化学结构如何，都可能在治疗早期以及长期暴露长达数年之后出现。估计的发生率被严重低估。由于血管性水肿起病较晚且通常为长期治疗，其表现未得到充分认识，实际发生率可能远高于此。此外，自发报告偏差也可能导致这一现象的实际发生率更高。在某些风险群体中，例如美国黑人，发生率可能更高（高达3倍）。治疗包括立即停用ACE抑制剂并进行急性症状支持治疗，随后立即（并长期）使用其他类药物进行替代治疗，以控制高血压和/或心力衰竭。旨在阐明ACE抑制剂相关血管性水肿潜在机制的临床前和临床研究尚未得出明确结论。有人认为免疫过程和几种介质系统（缓激肽、组胺、P物质和前列腺素）参与了血管性水肿的发病机制。所有综述报告中的很大一部分表明ACE抑制剂诱发的血管性水肿与（组织）缓激肽水平升高之间存在关联。然而，尚未找到缓激肽在血管性水肿中作用的确凿证据，而且缓激肽的唯一作用似乎不太可能。到目前为止，尚未找到免疫介导发病机制的确切证据。此外，有人提出ACE基因多态性和一些酶缺乏与ACE抑制剂诱发的血管性水肿有关。药物遗传学和分子生物学研究的进展应能更清楚地揭示ACE抑制剂相关血管性水肿发病机制中可能存在的遗传因素。
