Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction: A Network Meta-Analysis
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BACKGROUND: Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26-0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19-0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy. CONCLUSIONS: The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction.
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β-Blocker therapy is known to foster numerous clinical benefits in some subjects with CVD, including reduced risks of heart attack, stroke, heart failure and death.
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- Authors
- Burnett, H., Earley, A., Voors, A. A., Senni, M., McMurray, J. J. V., Deschaseaux, C., & Cope, S.
- Affiliations
- Novartis (Switzerland) (CH)
- Corresponding author
- Burnett, Heather
- Venue
- Circulation Heart Failure
- Published
- 2017-01
- Volume
- 10
- Issue
- 1
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC5265698
- OpenAlex
- W2577614303
- Cited by
- 238
- References
- 100
- Citations by year
- 2026: 4 · 2025: 19 · 2024: 20 · 2023: 18 · 2022: 45 · 2021: 42 · 2020: 33 · 2019: 33 · 2018: 15 · 2017: 9
- FWCI
- 19.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-nd
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by-nc-nd)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- heart failure with reduced ejection fraction, all-cause mortality, ACE inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, combination therapy, treatment efficacy comparison
- MeSH terms
- Network Meta-Analysis, Chronic Disease, Heart Failure, Humans, Stroke Volume, Randomized Controlled Trials as Topic, Treatment Outcome, Ventricular Dysfunction, Left
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