Implication of Mineralocorticoid Receptor Antagonist Esaxerenone in Patients With Heart Failure With Preserved Ejection Fraction

Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol — MMP-1 decreased by 35% (p<0,01), MMP-9 — by 56,3% (p<0,001), TIMP-1 — by 17,9% (p<0,01); nebivolol — MMP-1 decreased by 45% (p<0,001), MMP-9 — by 57,1% (p<0,001), TIMP-1 — by 30,1% (p<0,01); combination of bisoprolol with eplerenone — MMP-1 decreased by 43% (p<0,001), MMP-9 — by 51,2% (p<0,001), TIMP-1 — by 25,1% (p<0,01); combination of nebivolol with eplerenone — MMP-1 decreased by 53% (p<0,001), MMP-9 — by 64,3% (p<0,001), TIMP-1 — by 39% (p<0,01). In patients with NYHA class I HFmrEF after 12-month therapy, the decrease in MMP-1 level was 39,9% (p<0,01), MMP-9 — 57,5% (p<0,001). In class II, the decrease in MMP-1 level was 47% (p<0,001), MMP-9 — 49,7% (p<0,001). A significant decrease in TIMP-1 level was revealed in patients with class I by 29% (p<0,01), in patients with class II by 27,1% (p<0,01) compared with the initial data.Conclusion. A significant decrease in the levels of myocardial fibrosis markers (MMP-1, MMP-9, TIMP-1) was demonstrated in patients with HFmrEF of ischemic origin receiving long-term pharmacotherapy. The most pronounced effect was determined in patients with NYHA class I HF.

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Characterization of Mineralocorticoid Receptor Antagonist Therapy Initiation in High-Risk Patients With Heart Failure

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.116.002946 ◽

2017 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Lauren B. Cooper ◽

Bradley G. Hammill ◽

Eric D. Peterson ◽

Bertram Pitt ◽

Matthew L. Maciejewski ◽

...

Keyword(s):

Heart Failure ◽

High Risk ◽

Receptor Antagonist ◽

Mineralocorticoid Receptor ◽

Mineralocorticoid Receptor Antagonist ◽

Antagonist Therapy ◽

Therapy Initiation ◽

Patients With Heart Failure ◽

Risk Patients

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Epithelial Sodium Channel Genotype Is Associated with Elevated Potassium among Patients with Heart Failure Taking a Mineralocorticoid Receptor Antagonist

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2013.06.185 ◽

2013 ◽

Vol 19 (8) ◽

pp. S56

Author(s):

Alexandra Goncharenko ◽

Andrew Kadlec ◽

Adam Bress ◽

Shitalben Patel ◽

Orly Vardeny ◽

...

Keyword(s):

Heart Failure ◽

Sodium Channel ◽

Receptor Antagonist ◽

Mineralocorticoid Receptor ◽

Epithelial Sodium Channel ◽

Mineralocorticoid Receptor Antagonist ◽

Patients With Heart Failure

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Penggunaan Mineralocorticoid Receptor Antagonist pada Heart Failure Reduced Ejection Fraction

e-CliniC ◽

10.35790/ecl.v9i2.33144 ◽

2021 ◽

Vol 9 (2) ◽

pp. 379

Author(s):

David H. P. Sihombing ◽

Natalia C. I. Polii ◽

Agnes L. Panda

Keyword(s):

Heart Failure ◽

Literature Review ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Receptor Antagonist ◽

Mineralocorticoid Receptor ◽

Evaluation Study ◽

Mineralocorticoid Receptor Antagonist ◽

Reduced Ejection Fraction ◽

European Society Of Cardiology

Abstract: Heart failure reduction ejection fraction (HFrEF) is heart failure associated with decreased ejection fraction. It is characterized by abnormalities in cellular calcium regulation and changes in calcium kinetics that cause contraction changes in the myocardium. According to the European Society of Cardiology, mineralocorticoid receptor antagonist (MRA) is used as an adjunct drug when the first-line drugs are not sufficient to treat heart failure. This class of drugs has been shown to be very effective in use in HFrEF patients as shown in The Randomized Aldactone Evaluation Study (RALES), therefore, its use has been approved by the Food and Drug Administration (FDA). This study was aimed to analyze the effectiveness of MRA on HfrEF. This was a literature review study. The results showed that the use of MRA had significant benefits in reducing morbidity, mortality, and re-hospitalization in HFrEF patients. Improvements shown by the use of MRA included increased level of brain natriuretic peptide (BNP), improved NYHA classification, and decreased patient weight. A side effect that needs to be considered was hyperkalemia, whereas hypotensive effect was not of great concern because MRA was rarely reported to cause hypotension even when the initial systolic blood pressure is low. In conclusion, mineralocorticoid receptor antagonist is useful to improve the outome of HFrEF patients.Keywords: heart failure, heart failure reduced ejection fraction (HFrEF), mineralocorticoid receptor antagonist (MRA) Abstrak: Heart Failure reduced Ejection Fraction (HFrEF) merupakan gagal jantung disertai penurunan fraksi ejeksi. Kondisi ini ditandai dengan adanya kelainan regulasi kalsium seluler dan perubahan kinetika kalsium yang menyebabkan terjadinya perubahan kontraksi miokardium. Menurut European Society of Cardiology, mineralocorticoid receptor antagonist (MRA) digunakan sebagai obat tambahan bila obat lini pertama tidak cukup untuk mengatasi gagal jantung. Obat golongan ini terbukti sangat efektif digunakan pada pasien HFrEF sebagaimana yang ditunjukkan pada penelitian The Randomized Aldactone Evaluation Study (RALES), sehingga penggunaannya telah disetujui oleh Food and Drugs Administration (FDA). Penelitian ini bertujuan untuk menganalisis efektifitas penggunaan MRA pada pasien HFrEF. Jenis penelitian ialah literature review. Hasil penelitian memperlihatkan bahwa penggunaan MRA memiliki manfaat yang bermakna untuk menurunkan morbiditas, mortalitas, dan rawat inap ulang pada pasien HFrEF. Perbaikan yang ditunjukkan oleh penggunaan MRA antara lain peningkatan kadar Brain Natriuretic Peptide (BNP), perbaikan klasifikasi NYHA, dan penurunan berat badan pasien. Efek samping yang perlu menjadi pertimbangan ialah hiperkalemia, sedangkan efek hipotensi tidak terlalu dikhawatirkan karena MRA dilaporkan jarang menyebabkan hipotensi bahkan ketika tekanan darah sistolik awal rendah. Simpulan penelitian ini ialah mineralocorticoid receptor antagonist bermanfaat untuk memperbaiki luaran pada pasien HFrEF.Kata kunci: gagal jantung, heart failure reduced ejection fraction (HFrEF), mineralocorticoid, receptor antagonist (MRA)

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