The DOI matches its Crossref record, with a small difference in title or year; 47 of the 48 references it cites were found in a registry or an index.
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
Open accessAbstract
BACKGROUND AND METHODS: Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. RESULTS: The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients. CONCLUSIONS: Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.
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In the citing paper
“Steroidal MRA, such as spironolactone and eplerenone, have established cardiovascular bene fi ts in those with heart failure and are useful for treating primary hyperaldosteronism and refractory hypertension.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [157]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Steroidal MRA are standard of care for treatment of heart failure (particularly with reduced ejection fraction) and primary hyperaldosteronism.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [157]
Experimental — accuracy not yet measuredIn the citing paper
“Steroidal MRA are useful for management of heart failure as well as primary hyperaldosteronism and resistant hypertension.32,33”
In the citing paper
“Beta-blockers are effective at reducing all-cause death and hospitalization for HF in patients with HFrEF, with or without diabetes.[509][510][511][512]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [509]
In the citing paper
“Mineralocorticoid receptor antagonists (spironolactone, eplerenone) can also be effective antihypertensive agents (particularly for those with borderline or low potassium levels)89 and are important for morbidity and mortality reduction in patients with left ventricular dysfunction.90,91”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [91]
In the citing paper
“Many studies have reported the role of mineralocorticoid receptor blockers, such as spironolactone, not only in the treatment of hyperaldosteronism and resistant hypertension, but also in the prevention of metabolic and cardiovascular complications and cerebrovascular accidents in patients with normal values of aldosterone [17].”
From Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism (2022) · cites this paper as [17]
In the citing paper
“The mortality benefit of spironolactone in the RALES trial and eplerenone in the EMPHASIS-HF trial was consistent in T2DM and non-T2DM patients with HFrEF.158,159”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [158]
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Metadata
- Authors
- Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., Palensky, J., & Wittes, J.
- Affiliations
- University of Michigan (US)
- Cardiovascular Research Foundation (US)
- Centre Hospitalier Universitaire Henri-Mondor (FR)
- Statistics Collaborative (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1999-09-02
- Volume
- 341
- Issue
- 10
- Pages
- 709-717
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2323458614
- Cited by
- 9,214
- References
- 48
- Citations by year
- 2026: 264 · 2025: 279 · 2024: 273 · 2023: 298 · 2022: 335 · 2021: 309 · 2020: 326 · 2019: 295 · 2018: 298 · 2017: 304 · 2016: 344 · 2015: 351 · 2014: 366 · 2013: 383 · 2012: 398
- FWCI
- 198.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Nephrology › Potassium and Related Disorders
- Keywords
- spironolactone, severe heart failure, aldosterone receptor blockade, mortality, hospitalization for worsening heart failure, sudden cardiac death, gynecomastia, hyperkalemia, NYHA functional class, ACE inhibitors, loop diuretics, digoxin
- MeSH terms
- Aged, Mineralocorticoid Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Cause of Death, Diuretics, Double-Blind Method, Drug Therapy, Combination, Female, Gynecomastia, Heart Diseases, Heart Failure, Hospitalization, Humans, Hyperkalemia, Male, Middle Aged, Risk, Spironolactone, Survival Analysis
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