Angioedema induced by cardiovascular drugs: new players join old friends

Allergy. 2015 Oct;70(10):1196-200. doi: 10.1111/all.12680. Epub 2015 Jul 15.


During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin-angiotensin-aldosterone system (RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care.

Keywords: ACE inhibitor; angioedema; bradykinin type 2 receptor; icatibant; sacubitril.

Publication types

  • Review

MeSH terms

  • Angioedema / etiology*
  • Angioedema / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Bradykinin / metabolism
  • Cardiovascular Agents / adverse effects*
  • Humans
  • Renin-Angiotensin System / drug effects


  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Bradykinin