Angioedema associated with angiotensin II receptor antagonists: Challenging our knowledge of angioedema and its etiology

Introduction: Use of angiotensin converting enzyme inhibitors has long been associated with angioedema. Increased levels of bradykinin caused by the i nhibition of angiotensin converting enzyme have been thought to be responsi ble for this side effect. Angiotensin H receptor antagonists (AT2 blockers) , such as losartan potassium (Cozaar; Merck & Co., West Point, PA), are a n ew class of antihypertensives developed in part to eliminate cough and angi oedema. associated with ACE inhibitors. These agents act by selectively bin ding to angiotensin H receptor sites, thereby eliminating the hypertensive effects of angiotensin without affecting local and systemic bradykinin leve ls. We present three cases of AT2 receptor antagonist-induced angioedema, a nd examine its significance in the treatment of angioedema. and its propose d etiology. Methods: A retrospective chart review and review of the literat ure. Results. Three patients taking the AT2 blocker losartan presented with mucosal swelling in the head and neck clinically consistent with angioedem a. All three patients had prior episodes of angioedema while on losartan. T wo patients presented with involvement of the anterior tongue and face that resolved within 12 hours of discontinuation of the losartan and a course o f intravenous steroids. The third patient experienced recurring episodes of angioedema that eventually required a tracheotomy for airway compromise. A fter discontinuing the losartan and receiving a course of intravenous stero ids, the angioedema resolved in 5 days. The patient was decannulated 10 day s after onset of symptoms. Conclusion: Angioedema is a potentially life-thr eatening condition commonly associated with ACE inhibitor use. AT2 blockers bind to angiotensin II receptor sites and have no demonstrable effect on l ocal or systemic bradykinin levels. We present three cases that demonstrate AT2 blocker-induced angioedema. They were all complicated by the fact that the inciting agent, losartan, was not discontinued after the initial episo de and resulted in recurrent episodes of angioedema, one of which required surgical airway intervention. The incidence of AT2 blocker-induced angioede ma brings into question prior theories on the etiology of angioedema and br adykinins role in its pathogenesis.