Mineralocorticoid Receptor Antagonists Research Articles

Temporal trends in guideline-recommended medical therapy after an acute heart failure decompensation event: an observational analysis from Generator Heart Failure DataMart

ObjectivesTo evaluate the trend of prescription of the four foundational therapies, and their impact on 30-day urgent re-admissions and all-cause death in patients with heart failure and reduced ejection fraction...

Contemporary Management of Patients With Chagas Cardiomyopathy in Bolivia.

Chagas cardiomyopathy (CCM) is the debilitating result of a parasitic infection that causes structural and electrical abnormalities. Yet, optimal CCM management is challenging in the resource-poor communities where it predominates. The authors sought to investigate current practice patterns and barriers to CCM care through an online survey of cardiologists in Bolivia, the country with the highest CCM prevalence. Cardiologists were recruited through the national cardiologist directory. The Qualtrics survey was distributed anonymously. Survey questions were developed by Bolivian and U.S. researchers with extensive Chagas disease experience. Of 194 cardiologists, 67 (35%) completed≥80% of the survey. Responses were collected from every major Bolivian city. More than 70% of cardiologists cared for CCM patients daily or weekly. More frequent prescription of angiotensin-converting enzyme inhibitors (73%) and mineralocorticoid receptor antagonists (82%) for heart failure was reported compared to β-blockers. Ventricular tachycardia treatment was achieved more often with amiodarone (92%) than implantable cardioverter-defibrillators (46%). Anticoagulation was prescribed if CCM patients had atrial fibrillation (91%) or apical aneurysm with thrombus (86%), yet few cardiologists prescribed anticoagulation in left ventricular systolic dysfunction or CCM diagnosis alone. While pacemaker therapy was generally available to cardiologists (66%), patients received devices only through private insurance or philanthropy, with few physicians (28%) offering implantable cardioverter-defibrillators regularly. Cardiologists cited lack of device access as the predominant challenge in CCM management rather than insufficient knowledge or experience. These findings suggest that significant health equity gaps remain in CCM care, particularly in the availability of commonly indicated, potentially life-saving devices.

Mineralocorticoid receptor antagonists in end-stage renal disease under renal replacement therapies: bridging the gap between cardiovascular and systemic benefit, from heart failure to myocardial infarction.

Mineralocorticoid receptor antagonists in end-stage renal disease under renal replacement therapies: bridging the gap between cardiovascular and systemic benefit, from heart failure to myocardial infarction.

Nephrogenic Diabetes Insipidus Affecting Three Males in Two Generations—Case Report and Review of the Literature

Background: Nephrogenic diabetes insipidus (NDI) is defined as the inability of the kidney to concentrate urine owing to the insensitivity of the distal nephron to the antidiuretic hormone, arginine vasopressin. NDI is a heterogeneous rare autosomal dominant or X-linked disease. Objective: We present a family with nephrogenic diabetes affecting three males in two generations. Methods: We report two boys with NDI: a 4-month-old infant who was treated for fever, vomiting, and failure to thrive, and his 10-year-old uncle (the mother’s brother), who was admitted concurrently for consuming 11 L of fluid per day. According to family history, the mother’s sibling passed away at the age of two from severe hypernatremic dehydration. Results: The infant’s clinical and laboratory evaluation revealed a 7.8 mL/kg/h urine output, hypernatremic hyperchloremic alkalosis, extremely low urine density (1002), and elevated copeptin level. In contrast, the uncle’s clinical and laboratory evaluation revealed marked polyuria, low urine density, and elevated copeptin, all of which were suggestive of diabetes insipidus. After starting hydrochlorothiazide treatment (2 mg/kg/body), the infant’s urine production reduced (2.85 mL/kg/h); however, severe hypokalemia and alkalosis followed. Spironolactone, an aldosterone antagonist, were added, with good therapeutic response. Hydrochlorothiazide was administered to the uncle, and his daily fluid intake decreased to 3–4 L. Given the family history, Sanger sequencing for the AVPR2 variant was performed on the boys and the infant’s mother. Analysis showed hemizygous likely pathogenic variant c.335G>A p. (Cys112Tyr) in the 2 boys and heterozygous (carrier) status of the mother. Within the same family, we observed phenotypic heterogeneity: one child died at the age of two, another lived well into ten years without therapy, and a four month-old baby could have had a poor outcome without specific treatment. Conclusions: NDI is a rare and possibly fatal genetic disorder with heterogeneous manifestations. In families with a history of NDI, molecular genetic testing is crucial for family planning.

Implementation of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction (OpTIMa-HF Registry).

The last released European guidelines on the management of heart failure (HF) recommend in patients with chronic HF with reduced ejection fraction (HFrEF) a pharmacological approach based on four fundamental drugs to be rapidly implemented and then uptitrated to modify disease progression. The aim of the Optimization of Therapy in the Italian Management of Heart Failure (OPTIMA-HF) registry is to collect data on chronic HF outpatients in different settings of care. In the present analysis, we report the first analysis of the OPTIMA-HF registry, focusing on the real-life use of guideline-directed medical therapy in patients affected by HFrEF. OPTIMA-HF is an observational, cross-sectional, multicentre, real-life Italian registry conducted in two different clinical settings: HF outpatients' clinics of Italian hospitals and community HF outpatients' services. The study comprises a T0 phase-retrospective data collection, in which data of consecutive HF outpatients seen between January and October 2022 were collected; an educational activity phase; and a T1 phase-prospective data collection, in which data of consecutive HF outpatients seen between September 2023 and November 2023 were collected. In the present analysis, we describe the T0 phase focusing on HFrEF drug prescription rates, types, doses, combination therapy, the presence of contraindications and reasons of non-optimized treatment. Twenty-nine centres enrolled 2110 HF patients, of which 1390 (65.9%) had HFrEF [69.5±11.9years, 76.2% males, 4.1years since HF diagnosis, median ejection fraction (EF) 33%]. Among HFrEF patients, 89.1% were on treatment with renin-angiotensin-aldosterone system inhibitor (RAASi)/angiotensin receptor neprilysin inhibitor (ARNI) (72% ARNI and 17.1% RAASi), 95.1% with beta-blockers, 75.8% with mineralocorticoid receptor antagonists (MRA) and 63.2% with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Despite high prescription rates, a non-negligible number of patients with no contraindications were not treated with each specific drug. Patients taking all four drug classes, as recommended by guidelines, were mere 46.9%. Regarding doses, a still low number of patients on RAASi/ARNI and beta-blockers were treated with a dose ≥50% of the target doses recommended by the European guidelines. The OPTIMA-HF registry reported that HFrEF fundamental drugs are prescribed in most Italian patients; however, <50% of patients receive optimal combination therapy, and still not a satisfying number of patients receive target doses. Strategies to improve implementation of guideline-directed medical therapy are needed to improve HF prognosis.

Design considerations for future renoprotection trials in the era of multiple therapies for chronic kidney disease.

Nephrology has benefited from conducting increasingly large high-quality trials in the last 5-10 years. In addition to the long-standing known benefits of renin-angiotensin system inhibitors, we now have multiple pharmacotherapies that provide kidney and/or cardiovascular protection for certain types of patient with chronic kidney disease (CKD). These include sodium-glucose co-transporter 2 inhibitors (SGLT2i), a non-steroidal mineralocorticoid receptor antagonist and a glucagon-like peptide-1 receptor agonist. Trials of SGLT2i have had particularly important impact, as wide eligibility criteria in pivotal trials have enabled safety and efficacy across a wide range of causes of CKD to be demonstrated. These findings support the concept of final common pathways of CKD progression and should encourage similar trial designs recruiting broad ranges of patients at risk of CKD progression. This is important as these new drugs do not completely arrest CKD progression nor do they mitigate the full excess of cardiovascular disease. In the current era of multiple therapies to manage risk of CKD progression, trial design and conduct also need to consider new challenges. These include falling event rates, establishing standard of care for participants pre-randomization and improving the inclusion of trial participants understudied in previous trials. Streamlining trial design and conduct and reducing participation burden for patients and clinicians is increasingly important to facilitate larger sample sizes and to optimize adherence to study interventions and follow-up. Potential other solutions include maintaining a focus on wide generalizability (to include understudied patient groups) and empowering patients to volunteer for trials (through public and patient involvement and large-scale invitation methods), as well as innovations in trial design (including use of pre-randomization run-in periods to implement standard of care and factorial or platform trials to assess multiple treatments simultaneously).

Cardiovascular and Renal Outcomes with Ertugliflozin by Baseline Use of Renin–Angiotensin–Aldosterone System Inhibitors or Diuretics, Including Mineralocorticoid Receptor Antagonists: Analyses from the VERTIS CV Trial

Introduction: VERTIS CV was a placebo-controlled cardiovascular (CV) outcome trial evaluating the sodium-glucose cotransporter 2 inhibitor ertugliflozin in patients with type 2 diabetes and established atherosclerotic CV disease. The aim of the current analyses was to evaluate VERTIS CV cardiorenal outcomes according to baseline use of renin–angiotensin–aldosterone system (RAAS) inhibitors or diuretics, including mineralocorticoid receptor antagonists (MRAs). Methods: Participants received ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo once daily and were followed for a mean of 3.5 years. Prespecified CV and kidney outcomes were analyzed by Cox proportional hazard modeling in participant subgroups defined by baseline use of RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) or diuretics (loop diuretics, non-loop diuretics, MRAs), with interaction testing to assess for treatment effect modification. Results: A total of 8246 patients were randomized in VERTIS CV. At baseline, 6686 (81%) participants were being treated with RAAS inhibitors, 3542 (43%) with diuretics, 1252 (15%) with loop diuretics, and 674 (8%) with MRAs. No significant interactions were observed for cardiorenal outcomes by baseline use of RAAS inhibitors or MRAs (Pinteraction &gt; 0.05 for all). Statistically significant interactions for a first event of hospitalization for heart failure (HHF) or CV death, and of HHF (alone), were observed with baseline use of diuretics, including loop diuretics, with an increased benefit of ertugliflozin treatment versus placebo. Conclusion: In VERTIS CV, baseline use of diuretics, particularly loop diuretics, identified a subgroup that demonstrated greater benefit with ertugliflozin on first HHF/CV death and HHF outcomes, with no modification of treatment effect observed with baseline use of RAAS inhibitors or MRAs. There was no evidence of treatment effect on the kidney composite outcomes by baseline use of RAAS inhibitors, diuretics, loop diuretics, or MRAs. ClinicalTrials.gov identifier: NCT01986881

A brief approach to hypertension in type 2 diabetes mellitus

Type 2 diabetes mellitus (DM) and hypertension (HT) are common major cardiovascular disease (CVD) risk factors. They share common pathophysiological mechanisms and are commonly co-existent. Prevalence of HT is increased among diabetic patients but also DM is more common in hypertensive patients. CVD risk increases multiplicatively in coexistence of HT and DM. Lowering blood pressure (BP) has been shown to be associated with improved morbidity related to both macro- and micro-vascular complications. Although there is debate about target BP levels, in many randomized controlled trials and guidelines a goal of &lt; 130/80 mmHg is advocated in patients with DM, if well tolerated. However, an individualized approach should be cared for depending on risk factors, co-morbidities, and frailty of patients. Lifestyle modifications including weight loss, regular exercise, avoiding smoking and excessive alcohol consumption, and a healthy diet including limitation of salt and fat and total energy intake, are important both as a part of preventive therapy and treatment modality for both DM and HT. Among antihypertensive drugs angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are warranted due to their potential advantages for slowing albuminuria and progression to kidney failure which is more common in DM. Usually, their combination with calcium-channel blockers (CCBs) or thiazide/thiazide-like diuretics, in a step-wise manner, is recommended. Resistant HT is more common in DM and requires the addition of mineralocorticoid receptor antagonists (MRAs). New antidiabetic drugs like glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been found to lower BP. Apart from their antihypertensive effects they also improve CVD and renal outcomes. There’re ongoing new trials for new agents. Development of more potent and longer-term effective BP lowering drugs, single pill multiple drug combinations of antiHT agents and combination of antiHT agents with glucose-lowering and antilipidemic agents will probably improve compliance to treatment and achievement of goals in diabetic patients.

Inappropriate medication prescribing, polypharmacy, potential drug-drug interactions and medication regimen complexity in older adults attending three referral hospitals in Asmara, Eritrea: a cross-sectional study

BackgroundOlder adults often face several chronic illnesses that require them to take multiple medications. The increased number of prescribed medications has led to more complex medication regimens, putting older adults at a higher risk of potential drug-drug interactions, inappropriate medication prescribing, and adverse events. This study aimed to assess inappropriate prescribing practices, polypharmacy, medication regimen complexity, and their determinants in older adults.MethodsA cross-sectional study was conducted among older adults (aged 65 years and above) who visited three referral hospitals in Asmara, Eritrea, between June and August, 2023. A stratified random sampling technique was used, and data were collected from patient prescriptions, medical cards, and through interviews with a questionnaire. Inappropriate medication prescribing was evaluated using STOPP (Screening Tool of Older Person's Prescriptions)/ START (Screening Tool to Alert to Right Treatment) criteria version 3. Potential drug-drug interactions (pDDIs) and medication regimen complexity (MRC) were assessed using Lexi-comp drug interaction checker and MRC index, respectively. Descriptive statistics, logistic regression, Pearson’s correlation coefficient, independent samples t-test, one-way Analysis of Variance, and paired t-test were employed using IBM SPSS (version-26.0).ResultsA total of 430 respondents, with a similar male to female ratio, were included. The prevalence of polypharmacy was 5.3% (95%CI: 3.2, 7.5). Moreover, the prevalence of clinically significant pDDI was 51% (95%CI: 46, 56). The most common medicines involved in clinically significant pDDIs were enalapril (n = 179) and acetylsalicylic acid (n = 124). The presence of chronic illness (AOR = 7.58, 95%CI: 3.73, 15.39) and the number of drugs prescribed (AOR = 2.80, 95%CI: 1.91, 4.10) were predictors of clinically significant pDDIs. The prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were 27.4% (95% CI: 23.4, 31.8) and 13.3% (95% CI: 10.3, 16.7), respectively. The most common PIMs were long-acting sulfonylureas (n = 63) and aldosterone antagonists (n = 19). Besides, proton pump inhibitors (PPIs) (n = 41) and cardio-selective beta-blockers (n = 14) were the most common PPOs identified. Age (AOR: 0.95, 95% CI: 0.92, 0.98), presence of chronic illness (AOR: 1.51, 95% CI: 0.81, 2.80), and number of drugs prescribed (AOR: 2.01, 95% CI: 1.51, 2.69) were significant factors associated with PIM. MRCI score was a significant determinant of PPO (AOR: 1.25, 95% CI: 1.14, 1.38). The mean (SD) of the overall MRCI score was 9.1 (3.7), with dose frequency being the major contributor. The number of drugs prescribed was a determinant of MRCI score (r = 0.625, p < 0.001).ConclusionInappropriate medication prescribing and clinically significant drug-drug interactions were common among older adults, highlighting the need for immediate attention from policymakers, program managers, and healthcare professionals.

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.

Guideline-directed medical therapy implementation during hospitalization for cardiogenic shock.

Despite significant morbidity and mortality, recent advances in cardiogenic shock (CS) management have been associated with increased survival. However, little is known regarding the management of patients who survive CS with heart failure (HF) with reduced left ventricular ejection fraction (LVEF, HFrEF), and the utilization of guideline-directed medical therapy (GDMT) in these patients has not been well described. To fill this gap, we investigated the use of GDMT during an admission for CS and short-term outcomes using the Inova single-centre shock registry. We investigated the implementation of GDMT for patients who survived an admission for CS with HFrEF using data from our single-centre shock registry from January 2017 to December 2019. Baseline characteristics, discharge clinical status, data on GDMT utilization and 30day, 6month and 12month patient outcomes were collected by retrospective chart review. Among 520 patients hospitalized for CS during the study period, 185 (35.6%) had HFrEF upon survival to discharge. The median age was 64years [interquartile range (IQR) 56, 70], 72% (n=133) were male, 22% (n=40) were Black and 7% (n=12) were Hispanic. Forty-one per cent of patients (n=76) presented with shock related to acute myocardial infarction (AMI), while 59% (n=109) had HF-related CS (HF-CS). The median length of hospital stay was 12days (IQR 7, 18). At discharge, the proportions of patients on beta-blockers, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor/neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs) were 78% (n=144), 58% (n=107) and 55% (n=101), respectively. Utilization of three-drug GDMT was 33.0% (n=61). Ten per cent of CS survivors with HFrEF (n=19) were not prescribed any component of GDMT at discharge. Multivariable logistic regression adjusted for baseline GDMT use revealed that patients with lower LVEF and those who transferred to our centre from an outside hospital were more likely to experience GDMT addition (P<0.05). Patients prescribed at least one additional class of GDMT during admission had higher odds of 6month and 1year survival (P<0.01): On average, 6month survival odds were 7.1 times greater [confidence interval (CI) 1.9, 28.5] and 1year survival odds were 6.0 times greater than those who did not have at least one GDMT added (CI 1.9, 20.5). Most patients who survived CS admission with HFrEF in this single-centre CS registry were not prescribed all classes or goal doses of GDMT at hospital discharge. These findings highlight an urgent need to augment multidisciplinary efforts to enhance the post-discharge medical management and outcomes of patients who survive CS with HFrEF.

Mineralocorticoid Receptor Antagonist Use Among Patients With Chronic Kidney Disease Who Transitioned to Dialysis

Mineralocorticoid Receptor Antagonist Use Among Patients With Chronic Kidney Disease Who Transitioned to Dialysis

Real-world data on Empagliflozin and Dapagliflozin use in patients with HEART failure: The RED-HEART study.

We aimed to determine the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and to identify clinical factors associated with their use in patients with heart failure (HF) in a real-life setting. Real-world data on Empagliflozin and Dapagliflozin use in patients with HEART failure: The RED-HEART study is a multicentre, cross-sectional and observational study that included HF patients in the outpatient setting regardless of ejection fraction from 19 cardiology centres between August 2023 and December 2023. The study population consisted of 1923 patients with HF, predominantly men (61.2%), with a median age of 66 (range: 19-101) years. Overall, 925 patients (48.1%) were receiving SGLT2is. Among the study population, 22.1% had HF with preserved ejection fraction, 21.5% had HF with mildly reduced ejection fraction, 56.4% had HF with reduced ejection fraction and the use of SGLT2is was 42.0%, 47.9% and 50.6% in each group, respectively (P=0.012). The use of SGLT2is was 76.6% in patients with HF and diabetes, 19.8% in patients with HF and chronic kidney disease and 26.8% in patients without diabetes and chronic kidney disease (P<0.001). Higher education level [odds ratio (OR): 1.80; 95% confidence interval (CI): 1.06-3.05; P=0.027], higher household income (OR: 3.46; 95% CI: 1.27-9.42; P=0.015), New York Heart Association functional class IV (OR: 2.72; 95% CI: 1.16-6.35; P=0.021), diabetes (OR: 9.42; 95% CI: 6.72-13.20; P<0.001), the use of angiotensin receptor-neprilysin inhibitors (ARNis) (OR: 4.09; 95% CI: 2.39-7.01; P<0.001), the use of mineralocorticoid receptor antagonists (MRAs) (OR: 2.02; 95% CI: 1.49-2.75; P<0.001), the use of loop diuretics (OR: 1.62; 95% CI: 1.18-2.22; P=0.003) and the use of thiazide diuretics (OR: 1.72; 95% CI: 1.30-2.29; P<0.001) were independently associated with the use of SGLT2is. Conversely, atrial fibrillation (OR: 0.63; 95% CI: 0.45-0.88; P=0.008), chronic kidney disease (OR: 0.53; 95% CI: 0.37-0.76; P=0.001), the use of dihydropyridine calcium channel blockers (OR: 0.68; 95% CI: 0.48-0.98; P=0.042) and the use of statins (OR: 0.67; 95% CI: 0.49-0.91; P=0.010) were independently associated with the non-use of SGLT2is. The RED-HEART study provided comprehensive real-world data about implementing SGLT2is in patients with HF. These results suggest that there is a need for organized action and close collaboration between healthcare providers to improve the implementation of SGLT2is, especially in patients with HF with preserved ejection fraction and chronic kidney disease.

Myocardial contraction fraction predicts outcomes in patients enrolled in the TOPCAT trial.

Myocardial contraction fraction (MCF)-the ratio of left ventricular stroke volume to myocardial volume-is a volumetric measure of myocardial shortening that distinguishes between pathologic and physiologic hypertrophy. In this post-hoc analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, we investigated the prognostic value of MCF and its association with heterogeneity of treatment effect in heart failure with preserved ejection fraction (HFpEF). TOPCAT randomized patients with HFpEF to spironolactone or placebo. Patients with echocardiography data allowing for the calculation of MCF were included. The primary outcome was a composite of all-cause mortality, HF hospitalization, myocardial infarction, and stroke. 588 patients (median age 72.0 [63.0-79.3] years; 49.1 % female) were included. Median MCF was 27.0 % (21.8-32.8 %) for the overall group and was not different in the spironolactone and placebo groups. Over a median follow-up of 3.0 (1.9-4.5) years, MCF below median was associated with a worse prognosis (p = 0.003). On multivariable regression analysis (HR, 95 % CI), only New York Heart Association class (1.47, 1.14-1.91, p = 0.003) and MCF (0.76, 0.64-0.90, p = 0.001) were associated with the composite outcome. In this subset, spironolactone as compared to placebo was not associated with improved outcomes, but stratifying by MCF showed differential outcomes to spironolactone therapy (p = 0.010). Among patients with HFpEF enrolled in TOPCAT, reduced MCF was independently associated with worse outcomes. Larger prospectively designed studies are needed to further assess the role of MCF in patients with HFpEF.

Efficacy of Mineralocorticoid Receptor Antagonists on Kidney and Cardiovascular Outcomes in Patients With Chronic Kidney Disease: An Umbrella Review

Efficacy of Mineralocorticoid Receptor Antagonists on Kidney and Cardiovascular Outcomes in Patients With Chronic Kidney Disease: An Umbrella Review

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Data on the effect of mineralocorticoid receptor antagonist therapy on HbA1c levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial. In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally. Randomisation was performed with concealed allocation. The primary outcome of the trial was the composite of cardiovascular death and total (first and recurrent) heart failure events (ie, heart failure hospitalisation or urgent heart failure visit). In the present analysis, participants with diabetes at baseline (investigator-reported history of diabetes or baseline HbA1c ≥6·5%) were excluded. New-onset diabetes was defined as a HbA1c measurement of 6·5% or higher on two consecutive follow-up visits or new initiation of glucose-lowering therapy. The full-analysis set comprised all participants randomly assigned to study treatment, analysed according to their treatment assignment irrespective of the treatment received (ie, intention to treat). The safety analysis set comprised participants randomly assigned to study treatment who took at least one dose of the investigational product, analysed according to the treatment actually received. This trial is registered with ClinicalTrials.gov, NCT04435626, and is closed to new participants. Between Sept 14, 2020, and Jan 10, 2023, 6001 participants were recruited and randomly assigned to finerenone or placebo. 3222 (53·7%) participants did not have diabetes at baseline and comprised the study population. During a median duration of follow-up of 31·3 months (IQR 21·5-36·3), 115 (7·2%) participants in the finerenone group and 147 (9·1%) in the placebo group developed new-onset diabetes, corresponding to a rate of 3·0 events per 100 person-years (95% CI 2·5-3·6) in the finerenone group and 3·9 events per 100 person-years (3·3-4·6) in the placebo group. Compared with placebo, finerenone significantly reduced the hazard of new-onset diabetes by 24% (hazard ratio [HR] 0·76 [95% CI 0·59-0·97], p=0·026). Fine-Gray competing risk analysis, accounting for the competing risk of death, yielded a similar finding (subdistribution HR 0·75 [0·59-0·96], p=0·024). Results were similar in sensitivity analyses, in which the definition of new-onset diabetes was expanded to include initiation of SGLT2 inhibitor treatment with diabetes as indication, restricted to HbA1c measurements only, and restricted to new initiation of glucose-lowering drugs only (excluding SGLT2 inhibitor treatment). Findings were similar when participants treated with glucose-lowering drugs at baseline were excluded (n=15). The effect of finerenone, compared with placebo, on new-onset diabetes was consistent across key participant subgroups. Seven participants had an adverse event of new diabetes not captured by any of the definitions above. In participants with heart failure with mildly reduced or preserved ejection fraction without diabetes, oral finerenone reduced the hazard of new-onset diabetes, representing a meaningful additional clinical benefit of this treatment in these individuals. Bayer.

Cardiovascular Efficacy and Safety of Finerenone: A Meta-Analysis of Randomized Controlled Trials.

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has emerged as a novel therapeutic option for the management of patients with diabetes, chronic kidney disease, or heart failure. We seek to summarize the evidence on the drug's effectiveness regarding cardiovascular (CV) outcomes. We conducted a literature search of Pubmed, Cochrane CENTRAL, Embase, and ClinicalTrials.gov from inception to September 2024. Trials exploring the effects of finerenone on CV outcomes were extracted and analyzed. The results of pooled analyses were presented as risk ratios (RRs) with 95% confidence intervals (CIs). A total of eight trials, incorporating 21 200 patients, were included. The pooled analysis demonstrated a significant reduction in all-cause death (RR 0.92, 95% CI: 0.85-0.99), major adverse CV events (RR 0.85, 95% CI: 0.81-0.90), heart failure-related hospitalizations or unplanned hospital visits (RR 0.82, 95% CI: 0.76-0.87) with finerenone administration compared to control. Finerenone use was associated with a trend of reduced risk of CV death without reaching statistical significance (RR 0.90, 95% CI: 0.81-1.00). The risk of myocardial infarction (RR 0.91, 95% CI: 0.74-1.12), adverse events (RR 0.96, 95% CI: 0.89-1.03), adverse events leading to discontinuation (RR 1.06, 95% CI: 0.96-1.17) remained comparable across both groups. However, an increased risk of hyperkalemia (RR 2.07, 95% CI: 1.88-2.27) was observed with finerenone therapy compared to the control group. Finerenone administration was associated with improved CV outcomes in the CV-renmetabolic conditions compared to the control group.

651 Efficacy and safety of mineralocorticoid receptor antagonists in kidney transplant patients: an updated meta-analysis of randomized controlled trials

651 Efficacy and safety of mineralocorticoid receptor antagonists in kidney transplant patients: an updated meta-analysis of randomized controlled trials

WCN25-661 Switching Strategies: Evaluating the Safety and Efficacy of Non-Steroidal Mineralocorticoid Antagonists (ns MRA) in Spironolactone- non tolerant Post-Transplant Recipients

WCN25-661 Switching Strategies: Evaluating the Safety and Efficacy of Non-Steroidal Mineralocorticoid Antagonists (ns MRA) in Spironolactone- non tolerant Post-Transplant Recipients

Sodium zirconium cyclosilicate for MRAs optimization in HFrEF: lessons learned from the REALIZE-K trial.

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF), offering significant benefits in reducing mortality and hospitalizations. However, their use is often constrained by the risk of hyperkalemia, particularly in patients with chronic kidney disease. Patiromer and sodium zirconium cyclosilicate (SZC), two novel potassium binders, have emerged as highly effective and safe tools for managing hyperkalemia and enabling the optimization of MRA therapy. This mini-review critically examines the findings of the recently published REALIZE-K (Randomized Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate for the Management of Hyperkalemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction and Receiving Spironolactone) trial, placing it within the broader context of current evidence on potassium binders and their potential role in mitigating hyperkalemia to optimize MRA treatment. Moreover, it explores other significant barriers to MRA optimization, including clinician concerns over the risk of hyperkalemia, a consistent and pervasive issue that often leads to treatment inertia. By addressing both physiological and psychological barriers, this review aims to provide a comprehensive understanding of how to enhance MRA utilization and potentially improve clinical outcomes in patients with HFrEF.