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Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors
Abstract
Angioedema is a rare, potentially life-threatening adverse event of renin-angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients ≥100 and a duration of ≥8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval [CI] 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07%…
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“However, angioedema has been associated with the use of ACEi, with a weighted incidence of 0.30% (95% CI: 0.28 -0.32) reported in 1 systematic review.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [54]
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Metadata
- Authors
- Makani, H., Messerli, F. H., Romero, J., Wever-Pinzon, O., Korniyenko, A., Berrios, R. S., & Bangalore, S.
- Affiliations
- St. Luke's-Roosevelt Hospital Center (US)
- New York University (US)
- Corresponding author
- Messerli, Franz H.
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 110
- Issue
- 3
- Pages
- 383-391
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W2095519993
- Cited by
- 175
- References
- 65
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 13 · 2017: 14 · 2016: 13 · 2015: 14 · 2014: 16 · 2013: 17 · 2012: 3
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- angioedema, renin-angiotensin system inhibitors, ACE inhibitors, angiotensin receptor blockers, renin inhibitors, adverse drug reactions, heart failure, hypertension, coronary artery disease, drug safety comparison, placebo comparison
- MeSH terms
- Renin Inhibitors, Angioedema, Angiotensins, Female, Humans, Male, Middle Aged, Renin-Angiotensin System, Randomized Controlled Trials as Topic
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