Receptor Antagonists In Heart Failure Research Articles

Real-world effectiveness of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a retrospective, non-interventional cohort analysis

Background and purpose: Mineralocorticoid receptor antagonists (MRAs) have been shown in clinical trials to improve outcomes in heart failure with reduced ejection fraction (HFrEF). Yet, it is still uncertain how effective they are in real-world patients with HFrEF. This study aimed to investigate the association between MRAs and outcomes in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF). Methods: Patients diagnosed with HFrEF were included from the SwedeHF spanning from 2003 to 2020. Enrollment was based on medication dispensation within 3 months before and 6 months after the index date recorded in the register. Endpoints included all-cause mortality, cardiovascular death, and hospital re-admissions, tracked from the index date until censoring or occurrence of an event. Results: Of 47,103 patients identified through the SwedeHF with HFrEF, 22,368 individuals were not treated with MRA (referred to as MRA naive patients), 21,893 were treated with MRA at a dosage of 25 mg, and 1,423 were treated with MRA at 50 mg once daily. In the overall cohort, the administration of MRA at 25 mg was associated with modest reductions in the risk of all-cause mortality (hazard ratio: 0.92 [0.89–0.95], P < 0.0001) and cardiovascular death (hazard ratio: 0.93 [0.89–0.98], P < 0.01) compared to the MRA naive group. However, both dosages of MRA (25 and 50 mg) were associated with a slight increase in the risk of hospital re-admissions due to heart failure 10% compared to MRA naive patients. These findings were consistent when examining a propensity score-matched cohort. Interaction analysis showed a significantly improved survival rate for patients receiving MRA at 25 mg compared to MRA naive individuals, particularly among those with an estimated glomerular rate ≥30 mL/min/1.73 m2 across all patients and in those aged 70 years and above. Conclusions: The administration of MRA treatment at 25 mg once daily was linked to a modestly improved survival in a real-life HFrEF population, with even more pronounced benefits observed within a specific subgroup. This finding highlights the importance of personalized medicine in providing customized therapeutic advantages.

Patient Selection for Mineralocorticoid Receptor Antagonists in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.

The mineralocorticoid receptor is a steroid hormone receptor that contributes to cardiac tissue inflammation, fibrosis, and cardiac dysfunction and plays an important role in the pathophysiology of heart failure. Mineralocorticoid receptor antagonists (MRA) are an important component of guideline-directed medical therapy for heart failure to improve clinical outcomes. Clinical trial evidence in heart failure with reduced ejection fraction (HFrEF) informed a strong guideline recommendation for use of MRA in symptomatic patients, barring contraindications. In heart failure with mildly reduced ejection fraction (HFmrEF) and in heart failure with preserved ejection fraction (HFpEF), data are less robust, and this drug class received a weaker recommendation in the heart failure treatment guidelines. Thus, careful selection of patients with HFmrEF/HFpEF who are most likely to benefit from MRA is paramount to better optimize use of these medications. The purpose of this narrative review is to outline the rationale for the use of MRA in heart failure, summarize the clinical trial evidence for MRA in HFmrEF/HFpEF, discuss clinical considerations for their use, and describe investigations of nonsteroidal MRA in HFmrEF/HFpEF.

Korean Society of Nephrology 2022 recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Hyperkalaemia as a cause of undertreatment with mineralocorticoid receptor antagonists in heart failure.

To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up-titration of guideline-directed medical therapy (GDMT) in real-world settings. A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6months of up-titration. Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8years, mean EF of 29.4%). After up-titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P<0.0001), had lower EF (P=0.022), had higher NTproBNP (P=0.017), had lower eGFR (P=0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P<0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6months of up-titration of GDMT (P<0.0001). Among four groups, the incidence of hyperkalaemia throughout up-titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P<0.0001). In the MRA-naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6months of up-titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively. Hyperkalaemia increased significantly during up-titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Korean Society of Nephrology 2022 Recommendations on Controversial Issues in Diagnosis and Management of Hyponatremia.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Effect of Mineralocorticoid Receptor Antagonists in Heart Failure with Preserved Ejection Fraction and with Reduced Ejection Fraction - A Narrative Review.

Heart failure is a major cause of morbidity and mortality globally. By the end of this decade, ~8 million Americans will have heart failure with an expenditure of $69.8 billion. In this narrative review, we evaluate the benefits, potential risks and the role of Mineralocorticoid Receptor Antagonists (MRAs) in the management of both Heart Failure with Preserved Ejection Fraction (HFpEF) and Heart Failure with Reduced Ejection Fraction (HFrEF). We performed a comprehensive literature review to assess the available evidence on the role of MRAs in heart failure using the online databases (PubMed, Embase, Scopus, CINAHL and Google Scholar). Clinical evidence shows that MRAs such as spironolactone and eplerenone reduce mortality and readmissions for patients with HFrEF compared with placebo. Furthermore, one trial reported that MRAs reduce heart failure hospitalization in patients with HFpEF. The American College of Cardiology/American Heart Association Guidelines strongly recommend using MRA in patients with reduced Left Ventricular Ejection Fraction (LVEF) with Class II-IV symptoms, estimated glomerular filtration rate >30 ml/min/1.73 m2, and absence of hyperkalemia. Despite this, MRAs are underutilized in the management of heart failure. MRAs improve outcomes in patients with both HFpEF and HFrEF but remain underutilized.

Mineralocorticoid Receptor Antagonists in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with limited therapeutic options. Mineralocorticoid receptor antagonists (MRAs) have demonstrated improved clinical outcomes in heart failure with reduced ejection fraction (HFrEF), but their use in HFpEF remains controversial.

Mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction

Heart failure with reduced ejection fraction is associated with decreased functional capacity, poor quality of life and increased mortality risk. The neurohormonal compensatory response to a reduced cardiac output is mainly comprised of the sympathetic nervous system, natriuretic peptides and the renin–angiotensin–aldosterone system, which attempt to maintain peripheral perfusion. The renin–angiotensin–aldosterone system is an integral mechanism in increasing afterload by promoting angiotensin II-mediated vasoconstriction and increasing preload via the secretion of aldosterone which causes sodium and water retention. Albeit compensatory mechanisms attempt to increase cardiac output and perfusion, their effects are maladaptive as left ventricular function deteriorates in response to an increased afterload, preload and ventricular remodelling. In an attempt to interrupt this vicious circle, first-line pharmacological therapy in the treatment of heart failure is beta blockade and inhibition of the renin–angiotensin–aldosterone system. Integral to this treatment strategy are mineralocorticoid receptor antagonists, also known as aldosterone antagonists. This class of drug inhibits the action of aldosterone, decreases preload and reduces left ventricular workload, thus preserving ventricular function. This translates into reduced mortality incidence, decreased episodes of hospitalisations for cardiac causes and improvement in clinical signs and symptoms. Although patient benefits are explicit, adverse effects such as hyperkalaemia and renal impairment are associated with this therapy. Regular patient follow up and monitoring for potential adverse effects and drug interactions are essential to the success of the therapy.

Sex‐related differences in therapeutic response to mineralocorticoid receptor antagonists in heart failure: summarizing trial evidence

Sex‐related differences in therapeutic response to mineralocorticoid receptor antagonists in heart failure: summarizing trial evidence

The Role of Mineralocorticoid Receptor Antagonists in Heart Failure with Reduced Ejection Fraction.

Heart failure (HF) is a worldwide modern epidemic, associated with significant morbidity and mortality. Several causes have been identified for the syndrome, most of which share common pathophysiologic pathways, including neurohormonal activation. Central to the latter lies activation of the reninangiotensin- aldosterone system, and its effects on cardiovascular disease progression. The aim of this review is to summarize the pathophysiology of aldosterone and the effects of its blockage in the failing heart, as well as to provide state-of-the-art evidence, and address future perspectives regarding the use of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction. Literature was reviewed for studies that assess the pathophysiology of aldosterone in HF with reduced ejection fraction (HFrEF), and the effects of mineralocorticoid receptor antagonists (MRAs) in this condition. Several major society guidelines have synthesized the available evidence on HFrEF management, and drugs that block the renin-angiotensin-aldosterone system at different levels continue to form the key component of standard of care for these patients. Mineralocorticoid receptor antagonists are an important part of HFrEF pharmacologic treatment, and their use is supported by a high level of evidence studies. This class of drugs demonstrated significant benefits for morbidity and mortality, across the spectrum oh HFrEF, including patients after acute myocardial infarction. Current evidence supports the central role of aldosterone in HFrEF progression, and the significant benefits on outcomes with the use of MRAs.

Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry.

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF), but are underutilized. Hyperkalaemia may be one reason, but the underlying reasons for underuse are unknown. The aim of this study was to investigate the independent predictors of MRA underuse in a large and unselected HFrEF cohort. We included patients with HFrEF (ejection fraction <40%), New York Heart Association (NYHA) class II-IV and heart failure (HF) duration ≥6 months from the Swedish HF Registry. Logistic regression analysis identified independent associations between 39 demographic, clinical, co-treatment, and socioeconomic predictors and MRA non-use. Of 11 215 patients, 27% were women; mean age was 75 ± 11 years; only 4443 (40%) patients received MRA. Selected characteristics independently associated with MRA non-use were in descending order of magnitude: lower creatinine clearance (<60 mL/min), no need for diuretics, no cardiac resynchronization therapy/implantable cardioverter-defibrillator, higher blood pressure, no digoxin use, higher ejection fraction, outpatient setting, older age, lower income, ischaemic heart disease, male sex, follow-up in primary vs. specialty care, lower NYHA class, and absence of hypertension diagnosis. Plasma potassium and N-terminal pro B-type natriuretic peptide levels were not associated with MRA non-use. Mineralocorticoid receptor antagonists remain underused in HFrEF. Their use does not decrease with elevated potassium but does with impaired renal function, even in the creatinine clearance 30-59.9 mL/min range where MRAs are not contraindicated. MRA underuse may be further related to non-specialist care, milder HF and no use of other HF therapy.

Role of Aldosterone Receptor Antagonists in Heart Failure With Preserved Ejection Fraction

Aldosterone receptor antagonists have recently been added to the American College of Cardiology/American Heart Association/Heart Failure Society of America 2017 guideline update for serving a role in the reduction in morbidity in patients with heart failure with preserved ejection fraction and an ejection fraction greater than 45%. This recent addition to the heart failure with preserved ejection fraction recommendations is supported by the findings of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist study. All trials with spironolactone or eplerenone in the treatment of patients with heart failure with preserved ejection fraction are reviewed for both cardiovascular morbidity and mortality and symptom improvement. Limited positive data exist on the role aldosterone receptor antagonists has on mortality and symptom improvement in patients with heart failure with preserved ejection fraction. Ongoing trials with angiotensin receptor neprilysin inhibitor and sodium-glucose co-transporter 2 inhibitors in patients with heart failure with preserved ejection fraction are reviewed. This review provides the current clinical and scientific data pertaining to the safety and efficacy of aldosterone receptor antagonists in patients with heart failure with preserved ejection fraction.

Mineralocorticoid Receptor Antagonist in Heart Failure with Preserved Ejection Fraction

Mineralocorticoid Receptor Antagonist in Heart Failure with Preserved Ejection Fraction

Roles of Aldosterone Receptor Antagonists in Heart Failure, Hypertension, and Chronic Kidney Disease

Aldosterone receptor antagonists (AAs) antagonize the aldosterone hormone and prevent sympathetic activation, parasympathetic inhibition, and myocardial remodeling. In heart failure with reduced ejection fraction, AAs may be considered in patients who are symptomatic despite optimal doses of angiotensin-converting enzyme inhibitors and beta blockers, but it should not be used in the management of patients with preserved ejection fraction without other cormorbidities. AAs may be considered as an add-on in patients with inadequate control of blood pressure or in patients with primary hyperaldosteronism. Insufficient evidence is available for using AAs in chronic kidney disease patients.

Steroidal and Novel Non-steroidal Mineralocorticoid Receptor Antagonists in Heart Failure and Cardiorenal Diseases: Comparison at Bench and Bedside.

Characterization of mice with cell-specific deletion or overexpression of the mineralocorticoid receptor (MR) shed a new light on its role in health and disease. Pathophysiological MR activation contributes to a plethora of deleterious molecular mechanisms in the development of cardiorenal diseases like chronic kidney disease (CKD) and heart failure (HF). Accordingly, the available steroidal MR antagonists (MRAs) spironolactone (first generation MRA) and eplerenone (second generation MRA) have been shown to be effective in reducing cardiovascular (CV) mortality and morbidity in patients with chronic HF and a reduced left ventricular ejection fraction (HFrEF). However, they remain underutilized, in large part owing to the risk inducing severe adverse events including hyperkalemia and worsening of kidney function, particularly when given on top of inhibitors of the renin angiotensin system (RAS) to patients with concomitant kidney dysfunction. Novel, potent, and selective non-steroidal MRAs (third generation) were identified in drug discovery campaigns and a few entered clinical development recently. One of these is finerenone with different physicochemical, pharmacokinetics, and pharmacological properties in comparison with the steroidal MRAs. Available data from five clinical phase II trials with finerenone in more than 2,000 patients with HF and additional CKD and/or diabetes as well as in patients with diabetic kidney disease demonstrated that neither hyperkalemia nor reductions in kidney function were limiting factors to its use. Moreover, finerenone demonstrated a nominally improved outcome compared to eplerenone in a phase IIb trial with 1,066 patients with HFrEF and concomitant type 2 diabetes mellitus (T2DM) and/or CKD.

Clueless with fewer cues from endothelin. Commentary: Venous endothelin guides sympathetic innervation of the developing mouse heart.

Clueless with fewer cues from endothelin. Commentary: Venous endothelin guides sympathetic innervation of the developing mouse heart.

Abstract 9: Consistency of Laboratory Monitoring during Initiation of Mineralocorticoid Receptor Antagonists in Heart Failure

Introduction: The ACC/AHA heart failure guidelines recommend routine monitoring of serum potassium and renal function of patients treated with mineralocorticoid receptor antagonists (MRAs). However, compliance with these safety recommendations in routine clinical practice is unknown. Methods: We analyzed a cohort of Medicare beneficiaries in 10 states with prevalent heart failure as of July 1, 2011 and incident MRA use between May 1, 2011 and September 30, 2011. Medicare claims data were linked to laboratory results data from a large vendor. Outcomes included guideline recommended testing of serum creatinine and potassium prior to MRA initiation as well as follow-up testing in the early (day 1-10) and extended (day 11-90) post-initiation periods. Additional outcomes included abnormal laboratory results and adverse events proximate to MRA initiation. Results: We identified 10,443 Medicare beneficiaries with heart failure started on an MRA with 19.7% (2,056 of 10,443) initiated during a hospitalization. The table displays the frequency of laboratory testing before and after inpatient or outpatient MRA initiation. While overall 91.6% (9,564 of 10,443) of patients received appropriate pre-initiation testing, only 13.3% (1,384 of 10,443) received appropriate early post-initiation testing and 29.9% (3,122 of 10,443) received appropriate extended post-initiation testing. Among those patients initiated on an MRA during a hospitalization, 25.2% (518 of 2,056) had appropriate testing across all time periods. Chronic kidney disease was associated with increased likelihood of appropriate laboratory testing (RR 1.83, 95% CI: 1.58, 2.13), as was concomitant diuretic use (RR 1.78, 95% CI: 1.44, 2.21). In the early follow-up period, 1.8% (184 of 10,443) of overall patients started on a MRA had hyperkalemia or acute renal insufficiency requiring hospitalization or emergency department visit, and 8.7% (910 of 10,443) experienced these adverse events within the 90-day follow-up period. Conclusions: Rates of guideline recommended laboratory monitoring of creatinine and potassium after MRA initiation were low, which represents an area for quality improvement to ensure MRAs can safely and effectively be used in care of heart failure patients.

Evolving role for mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction.

The majority of randomized clinical trials in heart failure with preserved ejection fraction (HFpEF) have failed to show meaningful improvements in clinical outcomes. Recent randomized trials have shown benefits from mineralocorticoid receptor antagonists (MRAs) in the management of HFpEF. This review will focus on new evidence for MRA therapy in patients with HFpEF. Three randomized trials were reviewed: the Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial; the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial; and its echocardiography substudy. The Aldo-DHF trial showed improvements in echocardiographic measures of diastolic function. In the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial, hospitalization for heart failure was significantly reduced with MRA therapy with no difference in the primary outcome of cardiovascular death or hospitalization. In patients with high risk, however, there may be a reduction in cardiovascular mortality. We will also briefly discuss finerenone, a new generation MRA associated with a lower incidence of hyperkalemia. New evidence shows that MRA therapy decreases left ventricular mass and left atrial size, reduces hospitalization, and may reduce cardiovascular mortality in patients with high risk.

Relationship Between Galectin-3 Levels and Mineralocorticoid Receptor Antagonist Use in Heart Failure: Analysis From HF-ACTION

BackgroundGalectin-3 (Gal-3) is a marker of myocardial fibrosis, and elevated levels are associated with adverse outcomes. Mineralocorticoid receptor antagonists (MRAs) modulate cardiac fibrosis in heart failure (HF) patients and have been shown to improve long-term outcomes. We examined whether treatment effects from MRA use differed by Gal-3 levels in ambulatory heart failure patients enrolled in HF-ACTION. Methods and ResultsHF-ACTION was a randomized controlled trial of exercise training versus usual care in patients with HF due to LV systolic dysfunction (New York Heart Association functional class II–IV, left ventricular ejection fraction ≤0.35, median follow-up 2.5 years). Galectin-3 was assessed at baseline in 895 patients. The end point was all-cause mortality or all-cause hospitalization (ACM+ACH); all-cause mortality (ACM) was a key secondary end point. A differential association of MRA use by increasing Gal-3 concentration was tested with the use of interaction terms in Cox proportional hazards models, adjusted for covariates previously identified in this cohort as well as age, sex, and race. Inverse propensity-weighted (IPW) methods were also used to assess this association. Approximately one-half (n = 401) of the patients were on an MRA. There was no significant interaction for the associations of Gal-3 levels and MRA use for either end point (adjusted interaction P = .76 for ACM+ACH; P = .26 for ACM). There was no evidence of improved outcomes for patients on an MRA compared with those not on MRA for either end point (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.85–1.23, P = .8; and HR = 1.15, 95% CI [0.82–1.61], P = .4; respectively). IPW analysis was consistent with the results of the adjusted analysis. ConclusionOur study showed no evidence of interaction between Gal-3 and treatment effect of MRA. Whether biomarkers may be used to predict which patients may benefit from an mineralocorticoid receptor antagonist in HF requires further investigation.