Aim: Sodium-glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function.
Methods: This post-hoc analysis utilized data of the ROTATE-3 study, a randomized cross-over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro-hormonal markers and tubular sodium handling were assessed with mixed repeated measures models.
Results: The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin-eplerenone was -34.8% (95% CI -52.2, -10.9), -5.9% (95% CI -32.5, 31.3) and -28.1% (95% CI -48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin-eplerenone [32.2% (95% CI -1.5, 77.4)], compared with dapagliflozin [-12.5% (95% CI -35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin-eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI -10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI -879.2, -32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI -926.1, -120.0). Dapagliflozin-eplerenone decreased proximal absolute sodium reabsorption [-971.0 mmol/min (95% CI -1411.0, -531.0)], but did not affect distal absolute sodium reabsorption [-9.2 mmol/min (95% CI -402.0, 383.6)].
Conclusions: Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.
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http://dx.doi.org/10.1111/dom.15346 | DOI Listing |
Eur Heart J Case Rep
November 2024
Department of Cardiology, University of Athens Medical School, Hippokration General Hospital, 114 Vasilissis Sofias Avenue, Athens 11527, Greece.
Background: Behçet's disease (BD) is a multisystemic chronic inflammatory disorder. Cardiac manifestations in BD are extremely rare. There have been no reports of cardiac involvement of BD and especially endomyocardial fibrosis in the left ventricle (LV).
View Article and Find Full Text PDFTrends Cardiovasc Med
October 2024
Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address:
Optimal guideline-directed medical therapy for heart failure with reduced ejection fraction comprises the angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan), an evidence-based beta-blocker (bisoprolol, carvedilol, or sustained-release metoprolol), a mineralocorticoid antagonist (spironolactone or eplerenone), and a sodium-glucose cotransporter-2 inhibitor (dapagliflozin or empagliflozin). Optimal guideline-directed medical therapy for heart failure with preserved ejection fraction comprises a sodium-glucose cotransporter-2 inhibitor with emerging evidence to support the use of a mineralocorticoid antagonist and glucagon-like peptide-1 receptor agonists. This review will summarize the evidence behind the guideline recommendations, the impact of newer trials on management of patients with HF, and strategies for implementation into clinical practice.
View Article and Find Full Text PDFSci Rep
October 2024
INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Paris, France.
Acta Diabetol
September 2024
Department of Clinical Research, Hindu Mission Hospital, Tambaram, Chennai, 600045, Tamil Nadu, India.
Aim: We aim to explore the potential of diverse treatments, including perhexiline, calcium channel blockers, anti-hypertensives, PDE5 inhibitors, anti-anginal drugs, aldose reductase inhibitors, and SGLT-2 inhibitors, supported by clinical evidence. Additionally, this review seeks to identify novel therapeutic targets and future avenues for improving cardiovascular outcomes in diabetic populations.
Method: We performed a comprehensive literature review of English-language studies across multiple electronic databases, such as PubMed, ScienceDirect, Scopus, and Google Scholar, focusing on clinical trials.
Circulation
December 2024
Cardiovascular Division (B.L.C., A.S.D., M.A.P., S.D.S., M.V.), Brigham and Women's Hospital, Boston, MA.
Background: Kidney outcomes have been variably defined using nonstandardized composite end points in key heart failure trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists, the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan, and SGLT2 (sodium-glucose cotransporter-2) inhibitors on composite kidney end points using uniform definitions in 6 contemporary heart failure trials.
Methods: Individual participant-level data from trials of steroidal mineralocorticoid receptor antagonists (EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure], TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist] Americas), angiotensin receptor-neprilysin inhibitor (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], PARAGON-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in HF With Preserved Ejection Fraction]), and SGLT2 inhibitors (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure], DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]) were included.
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