Review
Meta-Analysis of Randomized Trials on the Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Patients ≥65 Years of Age

https://doi.org/10.1016/j.amjcard.2016.07.074Get rights and content

The comparative efficacy and safety of angiotensin-converting enzyme inhibitors (ACEIs) with other agents in patients ≥65 years of age with cardiovascular diseases or at-risk are unknown. Electronic databases were systematically searched to identify all randomized controlled trials that compared ACEIs with control (placebo or active) and reported long-term cardiovascular outcomes. We required the mean age of patients in the studies to be ≥65 years. Random-effects model was used to pool study results. Sixteen trials with 104,321 patients and a mean follow-up of 2.9 years were included. Compared with placebo, ACEIs significantly reduced all outcomes except stroke. Compared with active controls, ACEIs had similar effect on all-cause mortality (relative risk [RR] 0.99, 95% confidence interval [CI] 0.95 to 1.03), cardiovascular mortality (RR 0.99, 95% CI 0.93 to 1.04), heart failure (RR 0.97, 95% CI 0.91 to 1.03), myocardial infarction (RR 0.94, 95% CI 0.88 to 1.00), and stroke (RR 1.07, 95% CI 0.99 to 1.15). ACEIs were associated with an increased risk of angioedema (RR 2.79, 95% CI 1.05 to 7.42), whereas risk for hypotension and renal insufficiency was similar compared with active controls. Meta-regression analysis showed that the effect of ACEIs on outcomes remained consistent with age increasing ≥65 years. Sensitivity analysis excluding trials comparing ACEIs with angiotensin receptor blockers and heart failure trials yielded similar results, except for reduction in myocardial infarction. In conclusion, the efficacy of ACEIs was similar to active controls for mortality outcomes. Compared with placebo, there was evidence for reduction in cardiovascular outcomes; however, ACEIs failed to prevent stroke and increased the risk of angioedema, hypotension, and renal failure.

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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