Use of Angiotensin Receptor Blockers After Angioedema With an Angiotensin-Converting Enzyme Inhibitor

Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study

“…ACE is one of the key enzymes involved in the regulation of bradykinin levels and its inhibition by drugs such as ACEIs could elevate bradykinin levels, particularly when alternative degradation pathways are inhibited [9,10]. The lack of a direct effect of ARBs on the bradykinin degradation pathways accounts for the generally lower frequency of angioedema compared with ACEIs [6,8,11]. In a meta-analysis of 26 ACEI trials and 19 ARB trials, including seven head-to-head studies, the incidence of angioedema was reported as 0.30% and 0.11%, respectively [6].…”

“…In contrast, sacubitril/valsartan combines the ARB valsartan with a more specific inhibitor of neprilysin. The main reason for the difference between omapatrilat and sacubitril/valsartan may be the lower risk of angioedema with an ARB versus an ACE [6,8,11]. Additionally, the more specific inhibition of neprilysin may also contribute to a lower risk of angioedema [20][21][22][23][24].…”

The Role of Angiotensin Receptor Blockers in Patients with Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema

“…15 The updated risk of cross-reactive angioedema was determined to be 2.5% (95% CI 0 to 6.6) in possible cases and 1.5% (95% CI 0 to 5.1) in confirmed cases. In addition, the authors performed a sensitivity analysis including only randomized trials and found no significant difference between placebo and ARBs (OR 1.1; 95% CI 0.07 to 17).…”

“…Through this analysis, the authors deemed that ARBs could be an effective alternative to ACEIs in patients with angioedema, if the patient is educated about risks and benefits. 15 To our knowledge, no studies are being conducted to further examine this issue. If studies were to be conducted, they should be designed to look specifically at this outcome to define a true absolute risk and include a large enough number of patients such that pathophysiology and high-risk patients may be identified.…”

Investigating recurrent angio-oedema

“…3 4 A meta-analysis identified that the risk of any subsequent angio-oedema with angiotensin receptor blockers was 2.5% (1.5% for confirmed cases). 5 No test is available to determine who is at risk of angio-oedema induced by ACE inhibitors.…”