Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis.
Humans
Eplerenone
/ therapeutic use
Mineralocorticoid Receptor Antagonists
/ therapeutic use
Heart Failure
/ drug therapy
Spironolactone
/ therapeutic use
Treatment Outcome
Male
Risk Assessment
Gynecomastia
/ chemically induced
Aged
Risk Factors
Female
Middle Aged
Cause of Death
Time Factors
Recovery of Function
Aged, 80 and over
Adult
Eplerenone
Heart failure
MRA
Mineralocorticoid receptor antagonist
Spironolactone
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
30
05
2024
accepted:
07
08
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
13
9
2024
Statut:
epublish
Résumé
Eplerenone and spironolactone, recognized as mineralocorticoid receptor antagonists (MRAs), have been reported to improve clinical prognosis among individuals diagnosed with heart failure (HF). However, the difference in the clinical effects between eplerenone and spironolactone in individuals with HF remains uncertain. We aimed to assess the impact of eplerenone compared to spironolactone on clinical outcomes within the HF population. An extensive search was executed in several databases (PubMed, Web of Science, Scopus, Cochrane Library). All relevant studies evaluating eplerenone compared to spironolactone in patients with HF were included. Dichotomous data were pooled as Hazard ratio (HR) or Risk ratio (RR) with a 95% confidence interval (CI). Our main outcome was all-cause mortality. Secondary outcomes included death from cardiovascular causes, treatment withdrawal, and gynecomastia. Ten studies, comprising 21,930 HF individuals, were included in our investigation. Eplerenone showed a lower risk of all-cause mortality (HR = 0.78, 95%CI [0.64 to 0.94], P = 0.009) and cardiovascular mortality (HR = 0.54, 95%CI [0.39, 0.74], P = 0.0001) compared to spironolactone. Furthermore, eplerenone exhibited a reduced risk of treatment withdrawal (RR = 0.69, 95% CI [0.62, 0.78], P = 0.0001) and gynecomastia (RR = 0.07, 95% CI [0.02 to 0.31], P = 0.0001) than spironolactone. Eplerenone revealed lower all-cause and cardiovascular mortality events in comparison to spironolactone. Moreover, eplerenone was associated with lower gynecomastia and treatment withdrawal events compared to spironolactone. Further well-designed randomized controlled trials are still warranted better to identify the clinical differences between eplerenone and spironolactone. Protocol registration: https://doi.org/10.17605/OSF.IO/VNMGK.
Sections du résumé
BACKGROUND
BACKGROUND
Eplerenone and spironolactone, recognized as mineralocorticoid receptor antagonists (MRAs), have been reported to improve clinical prognosis among individuals diagnosed with heart failure (HF). However, the difference in the clinical effects between eplerenone and spironolactone in individuals with HF remains uncertain. We aimed to assess the impact of eplerenone compared to spironolactone on clinical outcomes within the HF population.
METHODS
METHODS
An extensive search was executed in several databases (PubMed, Web of Science, Scopus, Cochrane Library). All relevant studies evaluating eplerenone compared to spironolactone in patients with HF were included. Dichotomous data were pooled as Hazard ratio (HR) or Risk ratio (RR) with a 95% confidence interval (CI). Our main outcome was all-cause mortality. Secondary outcomes included death from cardiovascular causes, treatment withdrawal, and gynecomastia.
RESULTS
RESULTS
Ten studies, comprising 21,930 HF individuals, were included in our investigation. Eplerenone showed a lower risk of all-cause mortality (HR = 0.78, 95%CI [0.64 to 0.94], P = 0.009) and cardiovascular mortality (HR = 0.54, 95%CI [0.39, 0.74], P = 0.0001) compared to spironolactone. Furthermore, eplerenone exhibited a reduced risk of treatment withdrawal (RR = 0.69, 95% CI [0.62, 0.78], P = 0.0001) and gynecomastia (RR = 0.07, 95% CI [0.02 to 0.31], P = 0.0001) than spironolactone.
CONCLUSION
CONCLUSIONS
Eplerenone revealed lower all-cause and cardiovascular mortality events in comparison to spironolactone. Moreover, eplerenone was associated with lower gynecomastia and treatment withdrawal events compared to spironolactone. Further well-designed randomized controlled trials are still warranted better to identify the clinical differences between eplerenone and spironolactone.
TRIAL REGISTRATION
BACKGROUND
Protocol registration: https://doi.org/10.17605/OSF.IO/VNMGK.
Identifiants
pubmed: 39271992
doi: 10.1186/s12872-024-04103-7
pii: 10.1186/s12872-024-04103-7
doi:
Substances chimiques
Eplerenone
6995V82D0B
Mineralocorticoid Receptor Antagonists
0
Spironolactone
27O7W4T232
Types de publication
Systematic Review
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
489Informations de copyright
© 2024. The Author(s).
Références
Savarese G, Becher PM, Lund LH, Seferovic P, Rosano GMC, Coats AJS. Global burden of heart failure: a comprehensive and updated review of epidemiology. Cardiovasc Res. 2023;118:3272–87. https://doi.org/10.1093/cvr/cvac013 .
doi: 10.1093/cvr/cvac013
pubmed: 35150240
Heart Failure Society Of America null. HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2006;12:e1-2. https://doi.org/10.1016/j.cardfail.2005.11.005 .
doi: 10.1016/j.cardfail.2005.11.005
Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145:e895-1032. https://doi.org/10.1161/CIR.0000000000001063 .
doi: 10.1161/CIR.0000000000001063
pubmed: 35363499
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709–17. https://doi.org/10.1056/NEJM199909023411001 .
Masoudi FA, Gross CP, Wang Y, Rathore SS, Havranek EP, Foody JM, et al. Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998–2001. Circulation. 2005;112:39–47. https://doi.org/10.1161/CIRCULATIONAHA.104.527549 .
doi: 10.1161/CIRCULATIONAHA.104.527549
pubmed: 15983243
Witham MD, Gillespie ND, Struthers AD. Tolerability of spironolactone in patients with chronic heart failure – a cautionary message. Br J Clin Pharmacol. 2004;58:554–7. https://doi.org/10.1111/j.1365-2125.2004.02187.x .
doi: 10.1111/j.1365-2125.2004.02187.x
pubmed: 15521905
pmcid: 1884619
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21. https://doi.org/10.1056/NEJMoa030207 .
doi: 10.1056/NEJMoa030207
pubmed: 12668699
McMurray J, Cohen-Solal A, Dietz R, Eichhorn E, Erhardt L, Hobbs FDR, et al. Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice. Eur J Heart Fail. 2005;7:710–21. https://doi.org/10.1016/j.ejheart.2005.07.002 .
doi: 10.1016/j.ejheart.2005.07.002
pubmed: 16087129
Struthers A, Krum H, Williams GH. A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol. 2008;31:153–8. https://doi.org/10.1002/clc.20324 .
doi: 10.1002/clc.20324
pubmed: 18404673
pmcid: 6652937
Pardo-Martínez P, Barge-Caballero E, Bouzas-Mosquera A, Barge-Caballero G, Couto-Mallón D, Paniagua-Martín MJ, et al. Real world comparison of spironolactone and eplerenone in patients with heart failure. Eur J Intern Med. 2022;97:86–94. https://doi.org/10.1016/j.ejim.2021.12.027 .
doi: 10.1016/j.ejim.2021.12.027
pubmed: 35000806
Naser N, Durak-Nalbantic A, Sabanovic-Bajramovic N, Karic A. The effectiveness of eplerenone vs spironolactone on left ventricular systolic function, hospitalization and cardiovascular death in patients with chronic heart failure-HFrEF. Med Arch. 2023;77:105–11. https://doi.org/10.5455/medarh.2023.77.105-111 .
doi: 10.5455/medarh.2023.77.105-111
pubmed: 37260796
pmcid: 10227849
Yamamoto M, Seo Y, Ishizu T, Nishi I, Hamada-Harimura Y, Machino-Ohtsuka T, et al. Comparison of effects of aldosterone receptor antagonists spironolactone and eplerenone on cardiovascular outcomes and safety in patients with acute decompensated heart failure. Heart Vessels. 2019;34:279–89. https://doi.org/10.1007/s00380-018-1250-1 .
doi: 10.1007/s00380-018-1250-1
pubmed: 30203391
Cochrane Handbook for Systematic Reviews of Interventions n.d. https://training.cochrane.org/handbook . Accessed 29 Feb 2024.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71. https://doi.org/10.1136/bmj.n71 .
doi: 10.1136/bmj.n71
pubmed: 33782057
pmcid: 8005924
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5:210. https://doi.org/10.1186/s13643-016-0384-4 .
doi: 10.1186/s13643-016-0384-4
pubmed: 27919275
pmcid: 5139140
Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898. https://doi.org/10.1136/bmj.l4898 .
doi: 10.1136/bmj.l4898
pubmed: 31462531
The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [abstract] - Cochrane Methodology Register n.d. https://cmr.cochrane.org/?CRGReportID=2972 . Accessed 29 Feb 2024.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34. https://doi.org/10.1136/bmj.315.7109.629 .
doi: 10.1136/bmj.315.7109.629
pubmed: 9310563
pmcid: 2127453
Ferreira JP, Rossignol P, Machu J, Sharma A, Girerd N, Anker SD, et al. Mineralocorticoid receptor antagonist pattern of use in heart failure with reduced ejection fraction: findings from BIOSTAT-CHF. Eur J Heart Fail. 2017;19:1284–93. https://doi.org/10.1002/ejhf.900 .
doi: 10.1002/ejhf.900
pubmed: 28580625
Korol S, White M, O’Meara E, Tournoux F, Racine N, Ducharme A, et al. A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial. Am Heart J. 2018;204:190–5. https://doi.org/10.1016/j.ahj.2018.07.002 .
doi: 10.1016/j.ahj.2018.07.002
pubmed: 30097164
Larsson JE, Denholt CS, Thune JJ, Raja AA, Fosbøl E, Schou M, et al. Initiation of eplerenone or spironolactone, treatment adherence, and associated outcomes in patients with new-onset heart failure with reduced ejection fraction: a nationwide cohort study. Eur Heart J Cardiovasc Pharmacother. 2023;9:546–52. https://doi.org/10.1093/ehjcvp/pvad045 .
doi: 10.1093/ehjcvp/pvad045
pubmed: 37355774
Margolis J, Gerber RA, Roberts C, Gheorghiade M. Adherence to aldosterone-blocking agents in patients with heart failure. Am J Ther. 2010;17:446–54. https://doi.org/10.1097/MJT.0b013e3181ea3213 .
doi: 10.1097/MJT.0b013e3181ea3213
pubmed: 20844344
Nabati M, Tabiban S, Khani A, Yazdani J, Vafainezhad H. The effects of spironolactone and eplerenone on left ventricular function using echocardiography in symptomatic patients with new-onset systolic heart failure: a comparative randomised controlled trial. Heart Lung Circ. 2021;30:1292–301. https://doi.org/10.1016/j.hlc.2021.02.005 .
doi: 10.1016/j.hlc.2021.02.005
pubmed: 33744193
Schupp T, Von Zworowsky M, Reiser L, Abumayyaleh M, Weidner K, Mashayekhi K, et al. Effect of mineralocorticoid receptor antagonists on the prognosis of patients with ventricular tachyarrhythmias. Pharmacology. 2022;107:35–45. https://doi.org/10.1159/000520310 .
doi: 10.1159/000520310
pubmed: 34879385
Yamaji M, Tsutamoto T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, et al. Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure. Am Heart J. 2010;160:915–21. https://doi.org/10.1016/j.ahj.2010.04.024 .
doi: 10.1016/j.ahj.2010.04.024
pubmed: 21095280
Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21. https://doi.org/10.1056/NEJMoa1009492 .
doi: 10.1056/NEJMoa1009492
pubmed: 21073363
Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006;114:1829–37. https://doi.org/10.1161/CIRCULATIONAHA.106.649426 .
doi: 10.1161/CIRCULATIONAHA.106.649426
pubmed: 17030678
Sánchez-Más J, Turpín MC, Lax A, Ruipérez JA, Valdés Chávarri M, Pascual-Figal DA. Differential actions of eplerenone and spironolactone on the protective effect of testosterone against cardiomyocyte apoptosis in vitro. Rev Esp Cardiol. 2010;63:779–87. https://doi.org/10.1016/s1885-5857(10)70162-6 .
doi: 10.1016/s1885-5857(10)70162-6
pubmed: 20609311
Vukadinović D, Lavall D, Vukadinović AN, Pitt B, Wagenpfeil S, Böhm M. True rate of mineralocorticoid receptor antagonists-related hyperkalemia in placebo-controlled trials: A meta-analysis. Am Heart J. 2017;188:99–108. https://doi.org/10.1016/j.ahj.2017.03.011 .
doi: 10.1016/j.ahj.2017.03.011
pubmed: 28577687
Iqbal J, Parviz Y, Pitt B, Newell-Price J, Al-Mohammad A, Zannad F. Selection of a mineralocorticoid receptor antagonist for patients with hypertension or heart failure. Eur J Heart Fail. 2014;16:143–50. https://doi.org/10.1111/ejhf.31 .
doi: 10.1111/ejhf.31
pubmed: 24464876
Abuannadi M, O’Keefe JH. Review article: eplerenone: an underused medication? J Cardiovasc Pharmacol Ther. 2010;15:318–25. https://doi.org/10.1177/1074248410371946 .
doi: 10.1177/1074248410371946
pubmed: 20876342
Frankenstein L, Seide S, Täger T, Jensen K, Fröhlich H, Clark AL, et al. Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart failure (RESEARCH): a systematic review and network meta-analysis of randomized controlled trials. Heart Fail Rev. 2020;25:161–71. https://doi.org/10.1007/s10741-019-09832-y .
doi: 10.1007/s10741-019-09832-y
pubmed: 31364027
Yang P, Shen W, Chen X, Zhu D, Xu X, Wu T, et al. Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials. Heart Fail Rev. 2019;24:637–46. https://doi.org/10.1007/s10741-019-09790-5 .
doi: 10.1007/s10741-019-09790-5
pubmed: 31030322
Pamporis K, Karakasis P, Sagris M, Zarifis I, Bougioukas KI, Pagkalidou E, et al. Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a systematic review and network meta-analysis of 32 randomized trials. Curr Probl Cardiol. 2024;49:102615. https://doi.org/10.1016/j.cpcardiol.2024.102615 .
doi: 10.1016/j.cpcardiol.2024.102615
pubmed: 38692445