Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular and non-cardiovascular outcomes in patients at high/very-high cardiovascular risk without heart failure: a systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials
Key result
In patients at high/very-high CV risk without heart failure, ACE inhibitors reduced CV mortality compared to placebo (HR 0.88; 95% CI 0.78-0.99) and provided greater reduction than ARBs (P=0.03).
Why the study?
To assess the impact of ACE-Is and ARBs on all-cause and CV mortality, as well as CV, cerebrovascular, and renal outcomes in patients at high/very-high CV risk without heart failure.
Do ACE-Is and ARBs reduce mortality and cardiovascular events in patients at high/very-high CV risk without heart failure?
Population
87 908 participants at high/very-high CV risk without heart failure from 17 trials
Comparison
ACE-Is and ARBs vs placebo
Design
Systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials
Authors
Discussion
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Implication
Supports preferring ACE inhibitors over ARBs for CV protection in high-risk patients without HF; confirms mortality benefit vs placebo not seen with ARBs.
Study Design
Type
Meta-Analysis (n=87,908)
Blinding
double-blind
Randomization
randomized
Structured PICO
Do ACE-Is and ARBs reduce mortality and cardiovascular events in patients at high/very-high CV risk without heart failure?
P
Population
87,908 patients at high/very-high cardiovascular risk without heart failure included across 17 randomized, double-blind, placebo-controlled trials.
I
Intervention
Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs)
C
Comparator
Placebo
O
Outcome
All-cause and cardiovascular (CV) mortality, as well as CV, cerebrovascular, and renal outcomeshard clinical
Main Result
Hazard Ratio: 0.88 (95% CI 0.78–0.99)
In patients at high/very-high CV risk without heart failure, ACE inhibitors demonstrated a significant reduction in all-cause and CV mortality compared to placebo, whereas ARBs did not, suggesting ACE inhibitors should be preferred for CV protection.
Cite This Study
Masi et al. (2026) conducted a meta-analysis in high/very-high cardiovascular risk without heart failure (n=87,908). Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) vs. Placebo was evaluated on Cardiovascular mortality (HR 0.88, 95% CI 0.78-0.99). In patients at high/very-high CV risk without heart failure, ACE inhibitors reduced CV mortality compared to placebo (HR 0.88; 95% CI 0.78-0.99) and provided greater reduction than ARBs (P=0.03).