Minnebro (esaxerenone) / Daiichi Sankyo, Exelixis - LARVOL DELTA

Serum Potassium and Mineralocorticoid Receptor Antagonists As Modifiers of Atrial Arrhythmia Recurrence After Catheter Ablation for Atrial Fibrillation: A Narrative Review With Systematic Search and Mechanistic Synthesis. (PubMed, Cureus) - "We aimed to synthesize the clinical and mechanistic evidence on whether serum potassium, potassium-management strategies, and MRA therapy (steroidal: spironolactone, eplerenone; nonsteroidal: esaxerenone, finerenone) modify recurrence, and to derive a testable mechanistic framework. Current evidence supports avoiding hypokalemia and hyperkalemia, correcting reversible disturbances, and prescribing MRAs for established indications with appropriate monitoring; it does not justify routine potassium supplementation or MRA use solely to prevent post-ablation recurrence. Prospective, adequately powered randomized studies with longitudinal potassium assessment and rigorous rhythm monitoring are required before mechanism-based post-ablation interventions can be recommended."

Journal • Review • Atrial Fibrillation • Cardiovascular • Immunology

From Phenotypic Screening to Target and Compound Prioritization for Autosomal Dominant Polycystic Kidney Disease. (PubMed, SLAS Discov) - "A1AR affinity and subtype selectivity was a common denominator among ligands with CS-reducing activity, with the A1AR positive allosteric modulator MIPS521 showing the strongest effect. The workflow therefore generated a coherent A1AR-linked hypothesis and identified Esaxerenone as a compound-specific phenotypic hit; both require mechanistic confirmation and evaluation in additional disease models."

Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Oncology • Polycystic Kidney Disease • Renal Disease • PKD1 • PRKD1 • SLC2A1

Adrenalectomy versus esaxerenone: comparison of vascular benefits in patients with aldosterone-producing adenoma. (PubMed, J Hypertens) - "Compared with esaxerenone treatment, adrenalectomy provided more favorable improvements in vascular function and arterial stiffness in patients with APA. Nevertheless, esaxerenone also improved blood pressure, serum potassium levels, vascular function, and arterial stiffness, suggesting that it may be a beneficial treatment option for patients with APA who are inoperable or refuse surgery."

Journal • Cardiovascular • Endocrine Disorders

Emerging Pharmacological Therapies for Hypertension. (PubMed, Curr Hypertens Rev) - "This review provides a general overview of the physiological effects and pharmacokinetic properties that affect the absorption, distribution, metabolism, and elimination of recently developed antihypertensive drugs, such as fimasartan, azilsartan, zilebesiran, aprocitentan, and esaxerenone. Mechanistic differences among these agents are also highlighted; for instance, fimasartan and azilsartan inhibit the angiotensin II receptor, whereas other medications alter mineralocorticoid activity or endothelial pathways. The review further discusses the clinical implications of these mechanisms in hypertension management and supports informed therapeutic decisionmaking by providing a detailed understanding of the pharmacological and mechanistic profiles of these emerging antihypertensive therapies."

Journal • Cardiovascular • Hypertension

Cardiovascular events with esaxerenone versus spironolactone in hypertension. (PubMed, J Hum Hypertens) - "This finding was mainly attributable to risk reductions in heart failure (HR, 0.80; 95% CI, 0.70-0.92) and atrial fibrillation (HR, 0.63; 95% CI, 0.44-0.91), with associations for myocardial infarction (HR, 0.97; 95% CI, 0.48-1.96) and stroke (HR, 0.88; 95% CI, 0.64-1.19) being non-significant. Our analysis showed a reduced incidence of CVD associated with ESAX, pointing to potential drug-specific differences within the MRA class."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Metabolic Disorders • Myocardial Infarction

Effects of esaxerenone add-on therapy versus angiotensin II receptor blocker dose escalation on albuminuria and blood pressure in hypertensive patients with type 2 diabetes: An exploratory randomized study. (PubMed, J Diabetes Investig) - "In hypertensive patients with type 2 diabetes mellitus and albuminuria, esaxerenone add-on therapy reduced albuminuria and blood pressure more effectively than angiotensin II receptor blocker dose escalation but did not significantly reduce oxidative stress."

Journal • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Cardiorenal Effects of Switching from Eplerenone to Esaxerenone in Patients with Chronic Heart Failure and Hypertension: A Prospective Clinical Study. (PubMed, J Pers Med) - " In patients with chronic heart failure and hypertension, switching from eplerenone to esaxerenone was associated with reductions in blood pressure, BNP, UACR, and urinary osmolality, together with improvements in renal function. These findings suggest favorable physiological changes following the switch from a steroidal to a non-steroidal mineralocorticoid receptor antagonist, although confirmation in randomized controlled studies with clinical outcome measures is warranted."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Nephrology

Effect of Body Mass Index on the Efficacy and Safety of Esaxerenone Versus Trichlormethiazide for the Treatment of Japanese Patients with Uncontrolled Essential Hypertension: A Subanalysis of the Excite-HT Study. (PubMed, J Clin Hypertens (Greenwich)) - "Both drugs showed transient, modest decreases in creatinine-based estimated glomerular filtration rate that stabilized by Week 12. These exploratory findings, consistent with the primary study results, suggest that esaxerenone provides effective and well-tolerated BP control regardless of baseline BMI and may lower early-morning SBP to a greater extent than trichlormethiazide."

Clinical • Journal • Cardiovascular • Hypertension

Esaxerenone Attenuates Aldosterone-Induced Renal Fibrosis by Suppressing Fibroblast-to-Lymphatic Endothelial-like Cell Transdifferentiation. (PubMed, Int J Mol Sci) - "Our data suggest that aldosterone activates the MR and induces the transdifferentiation of fibroblasts into lymphatic endothelial-like cells via the MR/VEGFC/VEGFR-3 pathway, thereby promoting lymphangiogenesis. In addition, the administration of esaxerenone (a mineralocorticoid receptor blocker, MRB) to rats significantly suppresses this transdifferentiation and alleviates fibrosis."

Journal • Fibrosis • Immunology • FLT4 • VEGFC

The amount of sodium intake may affect the susceptibility to treatment with mineralocorticoid receptor antagonists in patients with primary aldosteronism. (PubMed, Clin Exp Nephrol) - "Although sodium restriction is suggested to facilitate attainment of post-treatment PRA ≥ 1.0 ng/mL/h, a marker of adequate aldosterone blockade, it remains uncertain whether achieving PRA ≥ 1.0 ng/mL/h is associated with favorable renal outcomes."

Journal • Cardiovascular • Endocrine Disorders

Esaxerenone versus angiotensin II receptor blockers as second-line therapy in older Japanese patients with uncontrolled hypertension on calcium channel blockers: the randomized, open-label ESCORT-HT study. (PubMed, Hypertens Res) - "Esaxerenone was non-inferior to ARBs in lowering morning home SBP and showed a favorable safety profile in older Japanese patients with inadequately controlled hypertension on amlodipine. These data support the clinical use of esaxerenone as an effective second-line treatment option for this population."

Journal • Cardiovascular • Hypertension

EFFECTS OF NON-STEROIDAL MINERALOCORTICOID RECEPTOR BLOCKER ESAXERENONE ON GLOMERULAR HEMODYNAMICS IN TYPE 2 DIABETIC KIDNEY DISEASE (ISN-WCN 2026) - "Introduction The non-steroidal selective mineralocorticoid receptor blocker (nsMRB) finerenone has demonstrated renoprotective effects in patients with type 2 diabetes and chronic kidney disease (CKD) (FIDELIO-DKD study). MR activity in MD cells thus regulates TGF responsiveness via the nNOS–NO pathway.Conclusion Correction of glomerular hyperfiltration in DKD by Esax involved the adenosine–A1aR pathway within TGF. MR activity in MD cells contributes to TGF regulation and may drive glomerular hyperfiltration in DKD.I have potential conflict of interest to disclose.This study was supported by a commissioned research grant from Daiichi Sankyo Co., Ltd.I did not use generative AI and AI-assisted technologies in the writing process."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • NGFR

MOLECULAR AND STRUCTURAL CHANGES IN BONE UNDER ALDOSTERONE-SALT HYPERTENSION UNCOVERED BY TRANSCRIPTOME-WIDE PROFILING (ISN-WCN 2026) - "These changes were associated with disrupted bone matrix gene regulation and were effectively prevented by mineralocorticoid receptor blockade. Our findings highlight a novel bone–kidney axis and support esaxerenone as a potential therapeutic agent for aldosterone-salt–induced osteopathy."

Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Hypertension • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Renal Disease • COL11A1 • COL1A1 • COL1A2 • FGF23

PROTEINURIA REDUCTION WITH ESAXERENONE IN CLINICAL PRACTICE: A CASE SERIES OF 17 PATIENTS (ISN-WCN 2026) - "Seven patients were receiving sodium–glucose cotransporter-2 (SGLT2) inhibitors at baseline and showed comparable reductions in UPCR.Conclusion Long-term treatment with esaxerenone demonstrated a sustained antiproteinuric effect in patients with CKD, including those without diabetes, with an acceptable safety profile. Given that reduction in proteinuria is recognized as a surrogate marker for future decline in kidney function, our findings suggest that esaxerenone may have beneficial effects across a broad range of patients with kidney impairment accompanied by proteinuria."

Clinical • Chronic Kidney Disease • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease

Industry Symposium 18: Hypertension Management Aimed at Achieving Target Blood Pressure: The Clinical Utility of Mineralocorticoid Receptor Antagonists (ISN-WCN 2026) - "2. They will also acquire practical knowledge of treatment approaches centered on mineralocorticoid receptor antagonists (MRAs), particularly esaxerenone, with the goal of achieving target blood pressure levels and improving clinical outcomes."

Clinical • Cardiovascular • Hypertension

Comment on: Efficacy and safety of esaxerenone vs trichlormethiazide for the treatment of uncontrolled essential hypertension in Japanese patients with type 2 diabetes mellitus: a subanalysis of the EXCITE-HT study. (PubMed, Hypertens Res) - No abstract available

Journal • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

Aldosterone-mineralocorticoid receptor interactions: new insights and therapeutic perspectives in primary aldosteronism. (PubMed, Hypertens Res) - "Finerenone has been demonstrated to have cardiovascular and renal benefits in patients with chronic kidney disease and type 2 diabetes, whereas esaxerenone has shown potent antihypertensive and antialbuminuric effects across diverse patient populations, including those with resistant hypertension and primary aldosteronism (PA), particularly in combination with renin-angiotensin system inhibitors. Nevertheless, clinical outcomes remain the most relevant endpoints, and MRAs continue to be a central therapeutic strategy in PA management. Mineralocorticoid receptor activation by aldosterone and modulatory factors: ASI aldosterone synthase inhibitor, ALDO aldosterone, HTN hypertension, MR mineralocorticoid receptor, MRA mineralocorticoid receptor antagonist, PA primary aldosteronism."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Endocrine Disorders • Fibrosis • Hypertension • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Positioning esaxerenone, a non-steroidal mineralocorticoid receptor antagonist, in the treatment of hypertension with and without hemodynamic cardiac stress. (PubMed, Hypertens Res) - No abstract available

Journal • Cardiovascular • Hypertension

Combined effect of esaxerenone and dapagliflozin on aldosterone-mediated sodium reabsorption and potassium excretion. (PubMed, Front Physiol) - "The findings indicate that Ald stimulates Na+ transport via the MR in the PT and regulates the expression of K+ channel genes. The MRB and SGLT2i combination may mitigate MRB-induced hyperkalemia, potentially by regulating TWIK-1 expression and maintaining K+ homeostasis."

Journal • Cardiovascular • Diabetic Nephropathy • Hypertension • Nephrology • Renal Disease

Efficacy and safety of esaxerenone vs trichlormethiazide for the treatment of uncontrolled essential hypertension in Japanese patients with type 2 diabetes mellitus: a subanalysis of the EXCITE-HT study. (PubMed, Hypertens Res) - "The overall incidence of serum potassium ≥5.5 mEq/L was 2.5% with esaxerenone and 0.9% with trichlormethiazide, with no cases of serum potassium ≥6.0 mEq/L. In this patient population, esaxerenone had a favorable safety profile, achieved blood pressure lowering similar to trichlormethiazide, and elicited a reduction of kidney damage (based on UACR), regardless of baseline antihypertensive agent or UACR."

Journal • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Type 2 Diabetes Mellitus

Aldosterone-Induced Renal Lymphangiogenesis and Endothelial-To-Mesenchymal Transformation to Promote Renal Interstitial Fibrosis Through the MR/TGF-β1 Pathway in Mice. (PubMed, Front Biosci (Landmark Ed)) - "Aldosterone induces inflammatory injury, thereby promoting renal lymphangiogenesis and EndMT."

Journal • Preclinical • Fibrosis • Immunology • CD68 • FLT4 • IL1B • LYVE1 • PDPN • TGFB1 • TNFA • VEGFC • VIM

A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice. (PubMed, Korean J Physiol Pharmacol) - "CS-3150 treatment reversed this effect, whereas the traditional MR antagonist eplerenone failed to do so at equivalent concentrations. In conclusion, CS-3150 improved insulin sensitivity in obese diabetic mice, likely through attenuation of adipose inflammation, reduction in fat accumulation, and enhancement of insulin signaling. These findings support the potential of CS-3150 as a therapeutic agent for obesity-associated metabolic dysfunction."

Journal • Preclinical • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • IL6 • VCAM1

Evidence-based validation of cardiovascular benefits from novel MRAs in type 2 diabetes: A meta-analysis of over 30,000 patients. (PubMed, J Diabetes Complications) - "This study provides high-certainty evidence supporting MRAs in reducing MACE and heart failure hospitalization, and moderate-certainty evidence for benefits on cardiovascular mortality. Cardioprotective effects may involve Ras, IL-17, and relaxin signaling."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus • EGFR • IL17A • MAPK10 • MMP1 • NOS2 • PACERR • PTGS2

Regulation of Klotho Production by Mineralocorticoid Receptor Signaling in Renal Cell Lines. (PubMed, Biomolecules) - "Using four renal cell lines, Madin-Darby canine kidney (MDCK), normal rat kidney, subtype 52E (NRK-52E), human kidney 2 (HK2) cells, and primary renal proximal tubule epithelial cells (RPTECs), and the four most frequently prescribed mineralocorticoid receptor blockers, spironolactone, eplerenone, finerenone, and esaxerenone, we assessed Klotho gene expression by qRT-PCR and Klotho protein by Western blotting. To conclude, common mineralocorticoid receptor antagonists are characterized by highly diverse effects on Klotho in four renal cell lines. Further studies are needed to define the role of mineralocorticoid receptor blockade for Klotho production."

Journal • Preclinical • Endocrine Disorders • Fibrosis • Heart Failure • Immunology • Inflammation • Nephrology • Renal Disease • KL

Molecular and Structural Changes in Bone Under Aldosterone-Salt Hypertension Uncovered by Transcriptome-Wide Profiling (KIDNEY WEEK 2025) - "These changes were associated with disrupted bone matrix gene regulation and were effectively prevented by mineralocorticoid receptor blockade. Our findings highlight a novel bone–kidney axis and support esaxerenone as a potential therapeutic agent for aldosterone-salt–induced osteopathy."

Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Hypertension • Osteoporosis • Renal Disease • COL1A1 • COL5A1 • FGF23