Nonsteroidal Mineralocorticoid Receptor Antagonists: Exploring Role in Cardiovascular Disease.

ABSTRACT: Aldosterone, a mineralocorticoid hormone, plays a role in the pathophysiology of many cardiovascular disease states. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in select patient populations. However, use of available steroidal receptor antagonists, eplerenone and spironolactone, is often limited by the risk or development of hyperkalemia. Nonsteroidal MRAs have been designed to overcome this limitation. The nonsteroidal MRAs have been studied in patients with heart failure with reduced ejection fraction, hypertension, and to lower the risk of cardiac and renal outcomes in those with type 2 diabetes and renal disease. In this review, the pharmacology of the MRAs is compared, the data evaluating the use of nonsteroidal MRAs are examined, and the place of this new generation of therapy is discussed. At this time, it seems that there could be a future role for nonsteroidal MRAs to reduce the risk of renal outcomes in high-risk individuals.

Management of noncardiovascular comorbidities in patients with heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction often have one or more noncardiovascular comorbidities. The presence of concomitant disease states is associated with worse outcomes, including increased risk of mortality, decreased quality of life, and increased healthcare resource utilization. Additionally, the presence of heart failure with reduced ejection fraction complicates the management of these comorbidities, including varying safety and efficacy of therapies compared to those without heart failure. This article will review the literature on the pharmacologic management of common noncardiovascular comorbidities-including chronic obstructive pulmonary disease, depression, diabetes mellitus, gout, chronic kidney disease, and iron deficiency-in patients with heart failure with reduced ejection fraction, as well as provide recommendations for appropriate treatment selection in this population.

Comparing Diuresis Patterns in Hospitalized Patients With Heart Failure With Reduced Versus Preserved Ejection Fraction: A Retrospective Analysis.

BACKGROUND: Congestion predominates in exacerbations of heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), but evidence suggests that excess volume may be distributed differently in these 2 subgroups. METHODS AND RESULTS: In this retrospective study, diuretic efficiency (DE, or net urine output per 40-mg of intravenous furosemide equivalent) during the first 72 hours was compared between patients hospitalized with HFrEF (n = 121) versus HFpEF (n = 120). Multivariate analysis was used to compare the 2 groups based on expected baseline differences (e.g., demographics, heart failure etiology, concomitant therapy). During the first 72 hours, mean daily diuretic doses were higher in patients with HFpEF versus HFrEF (172.0 vs. 159.9 mg, respectively, P = 0.026) but urine output was not significantly different (2603.3 mL vs. 2667.5 mL, respectively, adjusted P = 0.100). Similarly, mean cumulative DE did not differ (-673.5 vs. -637.8 mL/40-mg in the HFrEF and HFpEF groups, respectively, adjusted P = 0.884). An exploratory analysis of propensity-matched cohorts yielded similar findings. Correlations between the components of DE varied considerably and only became weak to moderately correlated toward the end of the observation period. CONCLUSIONS: Although cumulative DE did not differ between patients with HFrEF and HFpEF, variable correlations in the components of DE suggest there may be differences in diuretic response that warrant future analysis.

Through the Decades: ß-Blocker Use and Outcomes in Acute Coronary Syndromes.

Beta-adrenergic receptor antagonists, or ß-blockers, have been a cornerstone of treatment in patients with acute coronary syndromes (ACS) for more than 4 decades. First studied in the 1960s, ß-blockers in ACS have been shown to decrease the risk of death, recurrent ischemic events, and arrhythmias by reducing catecholamine-mediated effects and reducing myocardial oxygen demand. Through the decades, the ß-blocker of choice, timing of initiation, duration of therapy, and dosing have evolved considerably. Despite having clear benefits in certain patient populations (eg, patients with systolic dysfunction who are hemodynamically stable), the benefit of ß-blockers in other populations (ie, in patients at low risk for complications receiving modern revascularization therapies and optimal medical management) remains unclear. This article provides a review of the landmark clinical trials of ß-blockers in ACS and highlights the chronology and evolution of guideline recommendations through the decades.