Comparative Risk for Angioedema Associated With the Use of Drugs That Target the Renin-Angiotensin-Aldosterone System

Abstract

Background: Although certain drugs that target the renin-angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited. We assessed the risk for angioedema associated with the use of angiotensinconverting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren.Methods: We conducted a retrospective, observational, inception cohort study of patients 18 years or older from 17 health plans participating in the Mini-Sentinel program who had initiated the use of an ACEI (n=1 845 138), an ARB (n=467 313), aliskiren (n=4867), or a ␤-blocker (n = 1 592 278) between January 1, 2001, and December 31, 2010. We calculated the cumulative incidence and incidence rate of angioedema during a maximal 365-day follow-up period. Using ␤-blockers as a reference and a propensity score approach, we estimated the hazard ratios of angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex, history of allergic reactions, diabetes mellitus, heart failure, or ischemic heart disease, and the use of prescription nonsteroidal antiinflammatory drugs.Results: A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren, and 915 for ␤-blockers) were observed during the follow-up period. The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96) cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for ␤-blockers. The incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for ␤-blockers. Compared with the use of ␤-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81-3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04) for aliskiren.Conclusions: Compared with ␤-blockers, ACEIs or aliskiren was associated with an approximately 3-fold higher risk for angioedema, although the number of exposed events for aliskiren was small. The risk for angioedema was lower with ARBs than with ACEIs or aliskiren.

Epidemiology of ACE Inhibitor Angioedema Utilizing a Large Electronic Health Record

“…While angioedema is described during the first week of exposure in over half of cases, it can occur any time during the course of therapy. [11][12][13] A large retrospective study found that two-thirds of ACEI associated angioedema episodes occur within the first three months of therapy 11 while case reports have documented angioedema episodes that began after years of stable therapy. 14,15 A better understanding of when angioedema can occur from ACEI is needed to guide patient care.…”

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice

“…29 However, the RAAS modulator is known to produce potential side effects, such as angioedema, hypotension and acute pancreatitis by angiotensin receptor blocker, renin inhibitor and ACE inhibitors. [30][31][32] ACE inhibitors and angiotensin receptor blockers both cause cough and angioedema which produces cardiovascular risk in human. 33,34 Angiotensin II is more prone to causing vasoconstriction along with ischemic neuropathy by activation of the angiotensin receptor in the nervous system.…”

2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter

“…Although ARBs may be considered as alternative therapy for patients who have developed angioedema while taking an ACE inhibitor, there are some patients who have also developed angioedema with ARBs, and caution is advised when substituting an ARB in a patient who has had angioedema associated with use of an ACE inhibitor. [67][68][69][70] Clinical Recommendation(s) 2013 ACCF/AHA Guideline for Management of Heart Failure 24 1. ACE inhibitors are recommended in patients with HFrEF and current or prior symptoms, unless contraindicated, to reduce morbidity and mortality.…”