To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure

BackgroundMineralocorticoid receptor antagonists (MRAs) are pivotal in heart failure (HF) management.ObjectivesThis study evaluates their impact on adverse cardiovascular events and left ventricular ejection fraction (LVEF) in HF patients.MethodsA comprehensive literature search was conducted across...

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Main Authors: Jinyu He, Gang Chen, Yujia Huo, Chunyu Zhang, Haojie Xue, Jing Wang, Yi Zhong, Juan Xiao, Hongping Shen, Jian Feng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1564860/full
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author Jinyu He
Gang Chen
Yujia Huo
Chunyu Zhang
Haojie Xue
Jing Wang
Yi Zhong
Juan Xiao
Hongping Shen
Jian Feng
Jian Feng
author_facet Jinyu He
Gang Chen
Yujia Huo
Chunyu Zhang
Haojie Xue
Jing Wang
Yi Zhong
Juan Xiao
Hongping Shen
Jian Feng
Jian Feng
author_sort Jinyu He
collection DOAJ
description BackgroundMineralocorticoid receptor antagonists (MRAs) are pivotal in heart failure (HF) management.ObjectivesThis study evaluates their impact on adverse cardiovascular events and left ventricular ejection fraction (LVEF) in HF patients.MethodsA comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials databases, with a cutoff date of September 30, 2024. All included studies were randomized controlled trials (RCTs) that recorded the incidence of adverse cardiovascular events and changes in LVEF after MRA treatment in HF patients.ResultsA total of 30 randomized controlled trials involving 24,831 patients with heart failure were included. Compared to conventional therapy or placebo, treatment with MRAs significantly reduced the risk of all-cause mortality (RR = 0.862, 95% CI: 0.778–0.956, p = 0.005; I2 = 36.1%), cardiovascular mortality (RR = 0.828, 95% CI: 0.732–0.937, p = 0.003; I2 = 45.7%), and heart failure-related hospitalization (RR = 0.780, 95% CI: 0.657–0.926, p = 0.005; I2 = 65.5%). Moreover, MRAs significantly improved LVEF (WMD = 1.384, 95% CI: 0.208–2.559, p = 0.021; I2 = 59.9%). However, MRA therapy was associated with an increased risk of renal dysfunction, including hyperkalemia (RR = 2.086, 95% CI: 1.872–2.325, p < 0.001; I2 = 0.0%), elevated serum creatinine (RR = 1.512, 95% CI: 1.252–1.825, p < 0.001; I2 = 0.0%), decreased eGFR (WMD = −5.223, 95% CI: −7.380 to −3.066, p < 0.001; I2 = 0.0%), and potentially increased incidence of composite renal outcomes.ConclusionMRAs significantly reduce the risk of adverse cardiovascular events in patients with heart failure and contribute to LVEF improvement. They lower all-cause mortality in patients with HFrEF and reduce hospitalization for heart failure in those with HFmrEF or HFpEF. However, the potential risk of renal-related adverse events warrants close monitoring. Our protocol was registered in PROSPERO (registration number: CRD42024592012).
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spelling doaj-art-ee2525dda4b741df8c19088603eb8aa52025-08-20T03:13:50ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-07-011210.3389/fcvm.2025.15648601564860To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failureJinyu He0Gang Chen1Yujia Huo2Chunyu Zhang3Haojie Xue4Jing Wang5Yi Zhong6Juan Xiao7Hongping Shen8Jian Feng9Jian Feng10Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaClinical Pharmacy Office, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, Southwest Medical University Affiliated Hospital Medical Group Gulin Hospital (Gulin County People’s Hospital), Southwest Medical University, Luzhou, ChinaBackgroundMineralocorticoid receptor antagonists (MRAs) are pivotal in heart failure (HF) management.ObjectivesThis study evaluates their impact on adverse cardiovascular events and left ventricular ejection fraction (LVEF) in HF patients.MethodsA comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials databases, with a cutoff date of September 30, 2024. All included studies were randomized controlled trials (RCTs) that recorded the incidence of adverse cardiovascular events and changes in LVEF after MRA treatment in HF patients.ResultsA total of 30 randomized controlled trials involving 24,831 patients with heart failure were included. Compared to conventional therapy or placebo, treatment with MRAs significantly reduced the risk of all-cause mortality (RR = 0.862, 95% CI: 0.778–0.956, p = 0.005; I2 = 36.1%), cardiovascular mortality (RR = 0.828, 95% CI: 0.732–0.937, p = 0.003; I2 = 45.7%), and heart failure-related hospitalization (RR = 0.780, 95% CI: 0.657–0.926, p = 0.005; I2 = 65.5%). Moreover, MRAs significantly improved LVEF (WMD = 1.384, 95% CI: 0.208–2.559, p = 0.021; I2 = 59.9%). However, MRA therapy was associated with an increased risk of renal dysfunction, including hyperkalemia (RR = 2.086, 95% CI: 1.872–2.325, p < 0.001; I2 = 0.0%), elevated serum creatinine (RR = 1.512, 95% CI: 1.252–1.825, p < 0.001; I2 = 0.0%), decreased eGFR (WMD = −5.223, 95% CI: −7.380 to −3.066, p < 0.001; I2 = 0.0%), and potentially increased incidence of composite renal outcomes.ConclusionMRAs significantly reduce the risk of adverse cardiovascular events in patients with heart failure and contribute to LVEF improvement. They lower all-cause mortality in patients with HFrEF and reduce hospitalization for heart failure in those with HFmrEF or HFpEF. However, the potential risk of renal-related adverse events warrants close monitoring. Our protocol was registered in PROSPERO (registration number: CRD42024592012).https://www.frontiersin.org/articles/10.3389/fcvm.2025.1564860/fullheart failuremineralocorticoid receptor antagonistsall-cause mortalitycardiovascular deathmeta-analysis
spellingShingle Jinyu He
Gang Chen
Yujia Huo
Chunyu Zhang
Haojie Xue
Jing Wang
Yi Zhong
Juan Xiao
Hongping Shen
Jian Feng
Jian Feng
To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure
Frontiers in Cardiovascular Medicine
heart failure
mineralocorticoid receptor antagonists
all-cause mortality
cardiovascular death
meta-analysis
title To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure
title_full To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure
title_fullStr To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure
title_full_unstemmed To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure
title_short To MRAs treatment or not? evidence from a meta-analysis of randomized controlled trials of different MRAs on cardiovascular health in heart failure
title_sort to mras treatment or not evidence from a meta analysis of randomized controlled trials of different mras on cardiovascular health in heart failure
topic heart failure
mineralocorticoid receptor antagonists
all-cause mortality
cardiovascular death
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1564860/full
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