ReviewMeta-Analysis of Randomized Trials on the Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients ≥65 Years of Age
Section snippets
Methods
We performed a systematic search, without language restriction, using MEDLINE, Cochrane library, ClinicalTrials.gov, Embase, and Scopus databases from January 1, 1987, to March 1, 2016, for randomized controlled trials (RCTs) that compared ACEIs with placebo/active control and reported mortality and other cardiovascular outcomes. The search keywords included the following MeSH terms: (angiotensin-converting enzyme inhibitors OR ACEI OR benazepril OR captopril OR enalapril OR fosinopril OR
Results
Overall, 16 randomized trials8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 fulfilled all selection criteria for this meta-analysis (Supplementary Figure 1 available online only). The trials were either placebo controlled8, 11, 12, 15, 19, 22 or active comparator controlled.9, 10, 13, 14, 16, 17, 18, 21, 23 The Pilot Hypertension in the Very Elderly Trial (HYVET) had both placebo and active controlled arms.20 We excluded the combination arms (ACEIs plus ARBs) of the Ongoing
Discussion
In our meta-analysis of randomized trials predominantly involving patients ≥65 years of age, ACEIs significantly reduced all outcomes except stroke compared with placebo. However, compared with active controls, ACEIs had comparable results for all outcomes. When trials comparing ACEIs versus ARBs were excluded, ACEIs showed reduction in MI but still failed to reduce stroke. For safety outcomes, ACEIs were associated with increased risk for angioedema, hypotension, and renal insufficiency,
Disclosures
Dr. Bangalore is a consultant or has advisory relationships with the following companies: Daiichi-Sankyo, Pfizer, Abbott, and Boehringer Ingelheim. Dr. Messerli is a consultant or has advisory relationships with the following companies: Daiichi-Sankyo, Pfizer, Abbott, Servier, Medtronic, WebMD, Ipca, and Menarini. The other authors have no conflicts of interest to disclose.
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Angioedema With Normal Complement Studies: What Do We Know?
2023, Journal of Allergy and Clinical Immunology: In PracticeAngiotensin receptors in the kidney and vasculature in hypertension and kidney disease
2021, Molecular and Cellular EndocrinologyCitation Excerpt :While blockade of the RAS is commonplace in clinical medicine, it is important to note that there is significant residual risk of clinical events that remain. Moreover, the use of RAS inhibitors also imparts several side effects such as hyperkalemia (Ben Salem et al., 2014), acute kidney injury (Camin et al., 2015; Lapi et al., 2013; Townsend and Cohen, 2013), and angioedema (Faisant et al., 2016; Bavishi et al., 2016). Thus, this demonstrates the need to further understand the intricacies of the RAS.
ACE inhibitor-mediated angioedema
2020, International ImmunopharmacologyCitation Excerpt :Side effects of ACEi treatment include cough, angioedema (AE) and hyperkalemia. ACEi related angioedema (ACEi-AE) is an acquired, bradykinin-mediated form of AE; ACEi increase the risk of AE when compared to placebo (RR 2.29, 95% CI 1.02–5.15) or other active treatments (RR 2.79, 95% CI 1.05–7.42) [4]. The pathophysiologic basis of AE formation correlates with the role of ACE in bradykinin catabolism; additional predisposing factors may probably contribute to development of AE in a small subset of patients treated by ACEi.
Hereditary Angioedema: Insights into inflammation and allergy
2019, Molecular ImmunologyCitation Excerpt :AE-ACEi however can be life-threatening regardless of the dose and type of ACEi drug and results from a reduction in bradykinin degradation. A recent meta analysis of 16 randomized trials of ACEIs' safety and efficacy in patients above 65 years documented a 2.8‐fold increase in the risk of AE by ACEIs compared with controls (Bavishi et al., 2016). AE-ACEi usually involves the face, lips, tongue, and the arms, and other cutaneous sites being less commonly involved.
Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use?
2018, Journal of the American College of CardiologyCitation Excerpt :Most meta-analyses, as well as REACH cohort data, showed no difference in stroke rates between ARBs and ACE inhibitors in head-to-head comparisons. In our recent meta-analysis in older patients (>65 years old) with predominantly systolic hypertension, ACE inhibitors reduced CV outcomes compared with placebo, but the drugs notably failed to prevent stroke (38). ACE inhibitors are well tolerated in general, with a dry, irritating cough being their most common adverse effect.
Renin Angiotensin Aldosterone System Inhibitors in Hypertension: Is There Evidence for Benefit Independent of Blood Pressure Reduction?
2016, Progress in Cardiovascular DiseasesCitation Excerpt :At 3.7 years, there was no difference in CV events or mortality. Our recent meta-analysis involving trials with predominantly older patients showed no efficacy of ACEIs compared to active controls in reducing CV mortality, HF or stroke in elderly patients.61 The lack of superior efficacy of RAAS inhibitors in elderly could be related to its distinctly less efficacy in ISH which is the major form of HTN in this population.
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