Mineralocorticoid Receptor Antagonists Research Articles

Use of heart failure medical therapy before and after a cancer diagnosis: A longitudinal study.

We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs). We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non-cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR=1.51, 95% CI=1.35-1.68; beta-blockers: OR=1.22, 95% CI=1.08-1.37; MRAs: OR=1.31, 95% CI=1.08-1.59) and poor persistence (RASIs: OR=2.04, 95% CI=1.75-2.37; beta-blockers: OR=1.35, 95% CI=1.12-1.63; MRAs: OR=1.49, 95% CI=1.16-1.93), and higher risks for dose down-titration for RASIs (OR=1.69, 95% CI=1.40-2.04) and beta-blockers (OR=1.31, 95% CI=1.05-1.62). Cancer diagnosis was not associated with treatment initiation or dose up-titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs. Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF.

Assessing agreement between population-level administrative pharmaceutical databases and patient-reported medication dispensation in cardiac rehabilitation patients

BackgroundPharmacoepidemiology has emerged as a crucial field in evaluating the use and effects of medications in large populations to ensure their safe and effective use. This study aimed to assess the agreement of cardiac medication use between a provincial medication database, the Pharmaceutical Information Network (PIN), and reconciled medication data from confirmation through patient interviews for patients referred to cardiac rehabilitation. MethodsThe study included data from patients referred to the TotalCardiology Rehabilitation CR program, and medication data was available in both TotalCardiology Rehabilitation charts and PIN. The accuracy of medication data obtained from patient interviews was compared to that obtained from PIN with proportions and kappa statistics to evaluate the reliability of PIN data in assessing medication use. ResultsPatient-reported usage was higher for statins (41.6 %) vs. 38.4 %), ACE/ARB, beta-blockers (75.7 %) vs. 73.7 %), DOAC (3.5 %) vs. 2.6 %), and ADP-receptor antagonists (71.0 %) vs. 68.1 %) than if PIN was used. Patient-reported usage data was lower for Ezetimibe (4.7 vs. 4.8 %), Aldosterone antagonists (5.4 %) vs. 5.5 %), digoxin (0.9 %) vs. 1.0 %), calcium channel blockers (19.2 vs. 19.9 %) and warfarin (7.2 %) vs. 8.1 %). The results indicated that the differences between the two sources were very small, with an average agreement of 95.3 % and a kappa of 0.70. ConclusionThe studyʼs results, which show a high level of agreement between PIN and patient self-reporting, affirm the reliability of PIN data as a source for obtaining an accurate assessment of medication use. This finding is crucial in the context of pharmacoepidemiology research, where the accuracy of data is paramount. Further research to explore the complementary use of both data sources will be valuable.

Differences in the Approach to Guideline-Directed Medical Therapy in Patients with Heart Failure with Reduced Ejection Fraction: A Survey of Cardiologists, Internists, and Pharmacists.

Guideline-directed medical therapy (GDMT) has significantly improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, GDMT prescribing remains suboptimal. The purpose of this study was to survey cardiologists, internists, and pharmacists on their approach to GDMT prescribing. A survey containing 20 clinical vignettes of patients with HFrEF was answered by 127 cardiologists, 68 internists, and 89 pharmacists. Each vignette presented options for adjusting GDMT. Responses were dichotomized to the answer of interest. A mixed-effect model was used to calculate the odds of changing GDMT between pharmacists and physicians. Pharmacists were more likely to make changes to GDMT compared with internists (92.1% vs 82%; odds ratio [OR] 3.02 [1.50-6.06]; p=0.002). In medically-naïve patients, pharmacists were more likely to initiate beta-blockers than internists (45.4% vs 32.0%; OR 2.19 [1.00-4.79], p=0.049). Pharmacists were more likely than both internists and cardiologists to initiate mineralocorticoid receptor antagonists (34.4% vs 11.5%; OR 4.95 [2.41-10.18]; p<0.001 and 34.4% vs 13.9%; OR 3.95 [2.16-7.21]; p<0.001). Pharmacists were more likely than both internists and cardiologists to titrate beta-blockers (30.9% vs 16.4%; OR 3.15 [1.92-5.19]; p<0.001 and 30.9% vs 22.0%; OR 1.88 [0.18-2.87]; p=0.0030). Pharmacists were more likely than internists to titrate angiotensin receptor-neprilysin inhibitors (ARNI) (61.8% vs 34.1%; OR 3.54 [1.50-8.39]; p=0.004). The survey results show pharmacists were more likely to make any adjustments to GDMT than internists and cardiologists. Pharmacists prefer adding spironolactone and titrating beta-blockers compared with cardiologists and internists. Compared with only internists, pharmacists were more likely to initiate beta-blockers and titrate the dose of ARNI.

High-intensity care for GDMT titration.

Heart failure (HF) is a systemic disease associated with a high risk of morbidity, mortality, increased risk of hospitalizations, and low quality of life. Therefore, effective, systemic treatment strategies are necessary to mitigate these risks. In this manuscript, we emphasize the concept of high-intensity care to optimize guideline-directed medical therapy (GDMT) in HF patients. The document highlights the importance of achieving optimal recommended doses of GDMT medications, including beta-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter inhibitors to improve patient outcomes, achieve effective, sustainable decongestion, and improve patient quality of life. The document also discusses potential obstacles to GDMT optimization, such as clinical inertia, physiological limitations, comorbidities, non-adherence, and frailty. Lastly, it also attempts to provide possible future scenarios of high-intensive care that could improve patient outcomes.

Potential Role of Mineralocorticoid Receptor Antagonists in Nondiabetic Chronic Kidney Disease and Glomerular Disease.

Glomerular disease is a leading cause of CKD and ESKD. Although diabetic kidney disease is the most common cause of glomerular disease, nondiabetic causes include malignancy, systemic autoimmune conditions, drug effects, or genetic conditions. Nondiabetic glomerular diseases are rare diseases, with a paucity of high-quality clinical trials in this area. Furthermore, late referral can result in poor patient outcomes. This article reviews the current management of nondiabetic glomerular disease and explores the latest developments in drug treatment in this area. Current treatment of nondiabetic glomerular disease aims to manage complications (edema, hypertension, proteinuria, hyperlipidemia, hypercoagulability, and thrombosis) as well as target the underlying cause of glomerular disease. Treatment options include renin-angiotensin-aldosterone system inhibitors, statins/nonstatin alternatives, loop diuretics, anticoagulation agents, immunosuppressives, and lifestyle and dietary modifications. Effective treatment of nondiabetic glomerular disease is limited by heterogeneity and a lack of understanding of the disease pathogenesis. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs, such as finerenone), with their broad anti-inflammatory and antifibrotic effects, have emerged as valuable therapeutic options for a range of cardiorenal conditions, including CKD. ns-MRAs are an evolving drug class of particular interest for the future treatment of nondiabetic glomerular disease, and there is evidence that these agents may improve kidney prognosis in various subgroups of patients with CKD. The benefits offered by ns-MRAs may present an opportunity to reduce the progression of CKD from a spectrum of glomerular disease. Several novel ns-MRA are in clinical development for both diabetic and nondiabetic CKD.

Myocardial injury and clinical outcome in octogenarians after non-ST-elevation myocardial infarction.

The aim of this study was to analyze age-associated myocardial injury and clinical outcome after non-ST-elevation myocardial infarction (NSTEMI). This prospective, multicenter study consists of 440 patients with NSTEMI enrolled at 7 centers. All patients were treated with primary percutaneous coronary intervention and underwent cardiac magnetic resonance (CMR) imaging 1-10 days after study inclusion. CMR parameters of myocardial injury and clinical outcome were evaluated by creating 2 subgroups: <80 years vs. ≥80 years. The clinical endpoint was the 1-year incidence of major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure. Elderly patients ≥80 years accounted for 13.9% of the study population and showed a divergent cardiovascular risk profile compared to the subgroup of patients <80 years. CMR imaging did not reveal significant differences regarding infarct size, microvascular obstruction, left ventricular ejection fraction or multidimensional strain analysis between the study groups. At 1-year follow-up, MACE rate was significantly increased in patients ≥80 years compared to patients aged <80 years (19.7% vs. 9.6%; p = 0.019). In a multiple stepwise logistic regression model, the number of diseased vessels, aldosterone antagonist use and left ventricular global longitudinal strain were identified as independent predictors for MACE in all patients, while there was no independent predictive value of age regarding 1-year clinical outcome. This prospective, multicenter analysis shows that structural and functional myocardial damage is similar in younger and older patients with NSTEMI. Furthermore, in this heterogeneous but also clinically representative cohort with reduced sample size, age was not independently associated with 1-year clinical outcome, despite an increased event rate in patients ≥80 years.

A review of novel endothelin antagonists and overview of non-steroidal mineralocorticoid antagonists for treating resistant hypertension: An update

Several agents are emerging from five different novel classes of antihypertensive medications. We will focus on endothelin antagonists and non-steroidal mineralocorticoid receptor antagonists. While several agents exist in this later class, only a couple have demonstrated superior efficacy in resistant hypertension management. Endothelin receptor antagonists are effective therapy for primary and resistant hypertension, but they are not widely used. This is due to side effects demonstrated in large clinical trials, specifically increased peripheral edema and worsening heart failure in some cases, as well as the availability of many alternative agents to manage blood pressure effectively. However, the relationship between endothelin and its close ties to hypertension is evolving. Recent pre-clinical work explores new applications of more selective endothelin receptor antagonists. They suggest that specific subtypes of hypertension may benefit more from endothelin receptor blockade than simply those with primary hypertension. We review this topic and other related data. Lastly, we also provide a brief overview of non-steroidal mineralocorticoid receptor antagonists as some in the class show promise as antihypertensive agents.

New Therapeutics for Heart Failure Worsening: Focus on Vericiguat.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat's metabolism, molecular mechanisms, and drug-drug interactions.

Safety and Tolerability of Initiating Sacubitril-Valsartan With Spironolactone During Hospitalization for Acute Decompensated Heart Failure.

Background: Initiation of sacubitril-valsartan and mineralocorticoid receptor antagonists (MRA) during hospitalization for acute decompensated heart failure (ADHF) may be an ideal time to optimize guideline-directed medical therapy. However, there is limited research assessing the safety of combining these agents in the hospital. Methods: This was a multi-center, retrospective, propensity-score matched cohort study performed at 7 acute-care hospitals within a large health care system. All adult patients admitted with ADHF between January 1, 2019 to December 31, 2021 who received sacubitril-valsartan with MRA (MRA group) or without MRA (non-MRA group) and had a left ventricular ejection fraction (LVEF) < 40% were included in the study. Results: 220 patients were screened during the study time frame with 179 meeting inclusion criteria. Following propensity-score matching, 50 patients in the MRA group were matched to 50 patients in the non-MRA group. The overall incidence of adverse drug reactions (ADRs) was 24% in the non-MRA group compared to 20% in the MRA group (P = .629). There was a significantly greater incidence of hyperkalemia in the MRA group (0% vs 10%; P = .022). None of the patients in the non-MRA group were readmitted within 30 days due to an ADR compared to 6% in the MRA group (P = .079). Conclusion: The addition of spironolactone to sacubitril-valsartan in the hospital setting following stabilization of ADHF did not lead to a significantly greater incidence of overall ADRs, but patients were more likely to develop hyperkalemia and there was a numerically higher incidence of 30-day readmissions due to ADRs.

A Randomized trial assessing Efficacy and safety of Mineralocorticoid receptor Antagonist therapy compared to Standard antihypertensive Therapy in hypErtension with low Renin (REMASTER): rationale and study design

Low-renin hypertension affects 1 in 4 people with hypertension, but the optimal management of this condition is not known. We hypothesize that a large proportion of people with low-renin hypertension is mediated by excess mineralocorticoid receptor (MR) activation and that targeted treatment with an MR antagonist (MRA) will be beneficial. This randomized, single-blinded, titration-to-effect aims to investigate whether targeted treatment in low-renin hypertension with MRA is better compared to standard antihypertensives in terms of blood pressure control and end-organ protection. Adults with hypertension, who are treatment naïve or are receiving up to two antihypertensive agents and have a low direct renin concentration <10 mU/L will be included. Participants with severe hypertension, a secondary cause of hypertension, pregnant, breastfeeding, with moderate-severe cardiovascular and chronic kidney disease, or on medications that confound interpretation of the plasma direct renin or aldosterone concentrations will be excluded. Eligible participants will be randomized 1:1 to either MRA therapy (spironolactone) or standard anti-hypertensive therapy (perindopril+/− amlodipine) for 48 weeks. Anti-hypertensives will be up-titrated every 12 weeks until target blood pressure is achieved. The primary objective will be to determine the total defined daily dose of antihypertensives required to achieve the target blood pressure and change in mean clinic systolic blood pressure at week 48. Current hypertension guidelines do not have specific recommendations for the choice of anti-hypertensive medications for people with low-renin hypertension. The results of this trial could guide future hypertension guidelines.

The potential role of finerenone in patients with type 1 diabetes and chronic kidney disease.

Chronic kidney disease (CKD) represents a global health concern, associated with an increased risk of cardiovascular morbidity and mortality and decreased quality of life. Many patients with type 1 diabetes (T1D) will develop CKD over their lifetime. Uncontrolled glucose levels, which occur in patients with T1D as well as type 2 diabetes (T2D), are associated with substantial mortality and cardiovascular disease burden. T2D and T1D share common pathological features of CKD, which is thought to be driven by haemodynamic dysfunction, metabolic disturbances, and subsequently an influx of inflammatory and profibrotic mediators, both of which are major interrelated contributors to CKD progression. The mineralocorticoid receptor is also involved, and, under conditions of oxidative stress, salt loading and hyperglycaemia, it switches from homeostatic regulator to pathophysiological mediator by promoting oxidative stress, inflammation and fibrosis. Progressive glomerular and tubular injury leads to macroalbuminuria a progressive reduction in the glomerular filtration rate and eventually end-stage renal disease. Finerenone, a non-steroidal, selective mineralocorticoid receptor antagonist, is approved for treatment of patients with CKD associated with T2D; however, the benefit of finerenone in patients with T1D has yet to be determined. This narrative review will discuss treatment of CKD in T1D and the potential future role of finerenone in this setting.

Challenges to heart failure medication prescribing post-hospitalization.

To determine the prevalence of heart failure (HF) medication prescribing on discharge post-HF-related admission. A retrospective audit was conducted for 216 HF admissions over a period of 6 months; medication data from electronic records were collected for analysis. The prevalence of HF medication prescribing on discharge was: 32.9% (95% confidence interval: 26.6-39.6) renin-angiotensin-aldosterone system inhibitors, 10.6% (6.9-15.6) angiotensin receptor-neprilysin inhibitors, 31.5% (25.4-38.1) HF-specific beta-blockers, 42.6% (35.9-49.5) aldosterone receptor antagonists, and 11.6% (7.6-16.6) sodium-glucose cotransporter-2 inhibitors. HF medication prescribing remains relatively low despite the known benefits and recommendations listed in the guidelines.

New ways of mitigating aldosterone in cardiorenal disease.

Abstract Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease.

Predictors of ventricular tachyarrhythmia in patients with a wearable cardioverter defibrillator: an international multicenter registry.

Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440days (IQR 120-893). The primary study end point was the occurrence of sustained VT/VF. Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p = 0.027) and aldosterone antagonists (HR 0.7, p = 0.005) were associated with a significantly lower risk of VT/VF. Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF.

Effectiveness and safety of finerenone in Chinese CKD patients without diabetes: a retrospective, real-world study.

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has previously demonstrated its efficacy and safety in chronic kidney disease (CKD) associated with diabetes mellitus. Given its therapeutic potential, finerenone has been preliminarily explored in clinical practice for non-diabetic CKD patients. The effectiveness and safety in this population require further investigation in a real-world setting. This retrospective, real-world analysis included non-diabetic CKD patients receiving finerenone. The main clinical outcomes assessed were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum potassium (sK+) levels were also monitored. Data were collected at baseline, and then at 1month and 3months following treatment initiation. Totally, 16 patients were included. There was a notable decrease in UACR from 1-month post-treatment, with a further reduction at 3months, resulting in a median reduction of 200.41mg/g (IQR, 84.04-1057.10mg/g; P = 0.028; percent change, 44.52% [IQR, 31.79-65.42%]). The average eGFR at baseline was 80.16ml/min/1.73m2, with no significant change after 1month (80.72ml/min/1.73m2, P = 0.594) and a slight numerical increase to 83.45ml/min/1.73m2 (P = 0.484) after 3months. During the 3-month follow-up, sK+ levels showed only minor fluctuations, with no significant differences compared to baseline, and remained within the normal range throughout the treatment period. No treatment discontinuation or hospitalization due to hyperkalemia was observed. In non-diabetic CKD patients, finerenone showed good effectiveness and safety within a 3-month follow-up period. This study provides valuable real-world evidence supporting the use of finerenone in non-diabetic CKD and highlights the need for future large-scale prospective research to further validate its efficacy.

Cardiovascular and non-renal complications of chronic kidney disease: Managing risk.

Chronic kidney disease (CKD) currently affects approximately 850 million people globally and is continuing to increase in prevalence as well as in importance as a cause of death. The excess mortality related to CKD is mostly caused by an increase in cardiovascular disease. This includes atherosclerotic cardiovascular disease as many promoters of atherosclerosis, such as blood pressure, lipid levels and hypercoagulation, are increased in people with CKD. Diabetes is a leading cause of CKD contributing to the risk of CVD, and obesity is also increasingly prevalent. Management of these risk factors is therefore very important in CKD, and to reduce risk of CKD progression. Heart failure is also more prevalent in CKD and, again, many risk factors are shared. The concept of foundational pillars in the management of heart failure has been adapted to the treatment of CKD, with many organ-protective interventions, such renin-angiotensin system blockade, sodium-glucose cotransporter-2 inhibition and mineralocorticoid receptor antagonism, reducing the risk for mortality in heart failure with reduced ejection fraction, but also for progression of CKD. Atrial fibrillation is also more common with CKD and affects the management of the former. In this review these non-renal complications of CKD are discussed, along with how the risk of these complications should be managed. Many new opportunities have demonstrated heart and kidney organ protection, but implementation is a challenge.

Finerenone: Who should prescribe it for CKD? The physician associate's perspective.

Diabetic kidney disease (DKD) affects 30-40% of all patients with diabetes and contributes significantly to the cardiovascular burden of chronic kidney disease (CKD). Despite the availability of evidence-based medications like finerenone and simple screening tests such as Urinary Albumin-to-Creatinine Ratio (UACR), more resources are still needed to care for DKD patients. Physician Associates (PAs) play a crucial role in the multidisciplinary team responsible for DKD diagnosis, monitoring, and management. A nonsteroidal mineralocorticoid receptor antagonist, namely finerenone, was approved by the FDA in adults with CKD associated with type 2 diabetes to reduce the risk of renal and cardiovascular outcomes. Finerenone is considered among the pillars of care for DKD, furthermore, the addition of finerenone in combination with renin-angiotensin system inhibitors and/or other renal protective medications may offer additional benefits. Primary care providers prescribe finerenone less frequently than specialized care providers, indicating a need to empower physician associates in medication prescription and other renal protection strategies. As part of a multidisciplinary team, physician associates can play an important role in evaluating risk factors that contribute to heart disease and metabolic health. They can also monitor not only kidney function by ordering tests, such as serum creatinine and urinary albumin-to-creatinine ratio every 3-12months, but also serum potassium levels. Additionally, physician associates can encourage patients to take responsibility for their health by regularly monitoring their blood pressure, blood glucose levels, and body weight. With early detection and management, kidney failure and cardiovascular events may be preventable. Specialized physician associates also play a significant role in the comprehensive care of DKD patients, especially in the later stages. DKD care can be hindered by numerous factors such as lack of patient engagement during counseling, cost disparities, and a complex referral system that requires multidisciplinary guidelines to improve professional communication. It is necessary to re-envision the physician associates' role in primary care and empower them in goal-directed therapies.

Ongoing and Future Clinical Trials of Pharmacotherapy for Heart Failure.

Increasing knowledge of the processes leading to heart failure (HF) has allowed significant developments in therapies for HF over the past few decades. Despite the evolution of HF treatment, it still places a large burden on patients and health care systems across the world.We used clinicaltrials.gov to gather information about clinical trials as of August 2023 studying pharmacotherapy for HF. We included interventional trials that were "active, not recruiting", "recruiting", or looking for participants but "not yet recruiting". In total, 119 studies met our criteria of ongoing clinical trials studying novel as well as currently approved HF pharmacotherapies. The major interventions were novel medications/already approved medications for other diseases 29 % (34 trials), sodium-glucose co-transporter inhibitors 21 % (25 trials), angiotensin receptor blocker-neprilysin inhibitors 10 % (12 trials), diuretics 14 % (17 trials) and mineralocorticoid receptor antagonists 5 % (6 trials). Ongoing research will aid in reducing the impact of HF and we summarize clinical trials leading the way to better HF treatment in this review.

Aldosterone Effect on Cardiac Structure and Function.

Cardiac remodelling could be a key mechanism in aldosteronemediated cardiovascular morbidity and mortality. Experimental and clinical evidence has demonstrated that aldosterone causes cardiac structural remodelling and dysfunction by its profibrotic and pro-hypertrophic effects, which result mainly from the direct effects on myocardial collagen deposition, inflammation, and oxidative stress. Clinical studies have investigated the aldosterone effects on the heart in different clinical conditions, including general population, essential hypertension, primary aldosteronism, heart failure, and atrial fibrillation. Robust findings indicate that aldosterone or the activation of the cardiac mineralocorticoid receptor can cause damage to myocardial tissue by mechanisms independent of the blood pressure, leading to tissue hypertrophy, fibrosis, and dysfunction. Aldosterone-mediated cardiovascular morbidity and mortality mainly result from cardiac structural and functional alterations. In different clinical settings, aldosterone can induce cardiac structural remodelling and dysfunction via several pathological mechanisms, including cardiac fibrosis, inflammation, and oxidative stress. Aldosterone antagonists could effectively decrease or reverse the detrimental aldosterone-mediated changes in the heart.

Semaglutide in Chronic Kidney Disease: Great Enthusiasm. But How Does It Work?

Chronic Kidney Disease (CKD) is a clinical condition characterized by the progressive loss of kidney function. 10% of the world's population is affected by this condition, which represents the fifth leading cause of death globally. Furthermore, CKD is associated with increased risk of fatal and non-fatal cardiovascular events, and progression to end-stage renal disease. Over the last twenty years, an exponential growth in its prevalence and incidence has been observed. For this reason, various drugs have been developed and implemented in clinical practice, with various mechanisms, with the aim of reducing and minimizing this dramatic "cardio-renal" risk. These include SGLT2 inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists. However, a large proportion of CKD patients do not respond sufficiently to these treatments. GLP-1 receptor agonists represent a class of antidiabetic and nephroprotective drugs that are very promising in improving the prognosis of patients with CKD, especially if associated with one of the above-mentioned classes. In this article, we discuss the direct and indirect mechanisms through which one of the GLP-1 agonists, semaglutide, ensures nephro- and cardioprotection in patients with CKD and type 2 diabetes.