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High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and
Celina Borges Migliavaca1,2, Cinara Stein3, Verônica Colpani3
1Institute for Education and Research, Hospital Moinhos de Vento (HMV), Porto Alegre, RS, Brazil celinabm7@gmail.com.
Insights
High-dose ACE inhibitors (ACEIs) in heart failure (HF) patients showed no significant reduction in mortality or hospitalizations compared to low-dose ACEIs. However, high-dose ACEIs improved functional capacity but increased the risk of hypotension.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart failure (HF) management often involves angiotensin-converting enzyme inhibitors (ACEIs).
- Optimal dosing strategies for ACEIs in HF remain a subject of clinical debate.
- Evidence comparing low-dose versus high-dose ACEIs in HF requires systematic evaluation.
Purpose of the Study:
- To systematically review randomized controlled trials (RCTs) comparing low-dose versus high-dose ACE inhibitors (ACEIs).
- To assess the effects of different ACEI doses on mortality, hospitalizations, functional capacity, and side effects in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).
Main Methods:
- Searched major databases (PubMed, Embase, Cochrane CENTRAL, LILACS) up to January 2019.
- Included RCTs comparing low-dose vs. high-dose ACEIs in adult HFrEF patients.
- Performed meta-analysis and trial sequential analysis, assessing risk of bias and quality of evidence.
Main Results:
- Eight RCTs involving 5829 patients were analyzed.
- High-dose ACEIs showed non-significant effects on all-cause and cardiovascular mortality and hospitalizations.
- High-dose ACEIs improved functional capacity but increased the risk of hypotension; they decreased cough risk.
Conclusions:
- The benefits of high-dose ACEIs over low-to-intermediate doses in HF may be less than suggested by current guidelines.
- Findings support a more rational approach to HF management, focusing on strategies with the greatest net clinical benefit.
- Clinicians can use this evidence to optimize ACEI therapy for HFrEF patients.
Objective:
To systematically review evidence comparing the effect of low-dose versus high-dose ACE inhibitors (ACEIs) on all-cause and cardiovascular mortality and hospitalisation, functional capacity and side effects in patients with heart failure (HF).
Methods:
We searched PubMed, Embase, Cochrane CENTRAL and LILACS up to January 2019. We included randomised controlled trials (RCTs) comparing low-dose versus high-dose ACEIs in adults with HF with reduced left ventricular ejection fraction (HFrEF). Study selection and data extraction were performed by two independent reviewers. Risk of bias was assessed with RoB 2.0, and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We conducted random effects meta-analysis and trial sequential analysis.
Results:
We included eight RCTs (5829 patients with HF). In comparison with low-dose ACEIs, high-dose ACEIs showed a non-significant effect on all-cause mortality (8 RCTs, n=5828, relative risk (RR) 0.95, 95% CI 0.88 to 1.02; moderate quality of evidence), cardiovascular mortality (6 RCTs, n=4048, RR 0.93, 95% CI 0.85 to 1.01; moderate quality of evidence), all-cause hospitalisation (5 RCTs, n=5394, RR 0.95, 95% CI 0.82 to 1.10; moderate quality of evidence) and cardiovascular hospitalisation (4 RCTs, n=5242, RR 0.98, 95% CI 0.83 to 1.17; low quality of evidence). High-dose ACEI increased functional capacity (4 studies, n=555, standardised mean difference 0.38, 95% CI 0.20 to 0.55; low quality of evidence) and the risk of hypotension (4 RCTs, n=3783, RR 1.64, 95% CI 1.30 to 2.05; moderate quality of evidence). High-dose ACEI had no effect on dizziness (3 RCTs, n=4994, RR 1.37, 95% CI 0.97 to 1.93; low quality of evidence), but decreased the risk of cough (4 RCTs, n=5146, RR 0.85, 95% CI 0.73 to 0.98; moderate quality of evidence).
Conclusions:
The magnitude of benefit of using high dose versus low to intermediate doses of ACEIs might be less than traditionally suggested in clinical guidelines. These findings might help clinicians address the complex task of HF management in a more rational and timely fashion, saving efforts to implement strategies with the greatest net clinical benefit.
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