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.

Coexistence of Angioedema Alone with Impaired Glucose Tolerance

“…Further trials should include CSU patients with wheals and angioedema in order to test if patients with this subtype share the glucose metabolism profiles of CSU patients with or without angioedema. The strongest point of our study is that we applied rigorous inclusion and exclusion criteria to make sure that the recurrent angioedema patients we studied were CSU patients and not patients with bradykinin-mediated angioedema or other forms of recurrent angioedema, as has been described in other studies [18,19,20,21]. …”

Angioedema due to fixed dose combination of telmisartan plus ramipril

“…A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren) has been observed with adjusted hazard ratios to be 3.04 (95% confidence interval [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 in one of the study. [5]…”

“…The risk for angioedema has been suggested lower with ARBs than with ACEIs or aliskiren. [5] However, many isolated reports do exist, reporting angioedema with ARBs such as olmesartan medoxomil, valsartan, losartan and telmisartan. [6789]…”

Priorities for Cardiovascular Outcomes Research

“…Such efforts have demonstrated that distributed research networks can provide valuable insight into disease surveillance and comparative effectiveness research. [54][55][56][57] The Patient-Centered Outcomes Priorities for Cardiovascular Outcomes Research…”