Drug Insight: Aldosterone-Receptor Antagonists in Heart Failure

Table 1.

Major Inclusion and Exclusion Criteria of RALES and EPHESUS

Box 1.

Impaired renal function is a risk factor for hyperkalemia during treatment with aldosterone-receptor antagonists. The risk of hyperkalemia increases progressively when serum creatinine exceeds 141.0 µmol/l (1.6 mg/dl).^a In elderly patients or others with low muscle mass in whom serum creatinine does not accurately reflect glomerular filtration rate, it is recommended that glomerular filtration rate or creatinine clearance exceeds 0.5 ml/s (30.0 ml/min)
Aldosterone-receptor antagonists should not be administered to patients with baseline serum potassium in excess of 5.0 mmoI/l (5.0 mEq/l)
An initial dose of 12.5 mg spironolactone or 25.0 mg eplerenone is recommended, after which the dose can be increased to 25.0 mg spironolactone or 50.0 mg eplerenone if appropriate
The risk of hyperkalemia is increased with concomitant use of higher doses of angiotensin-converting-enzyme inhibitors (?75 mg captopril daily; ?10 mg enalapril or lisinopril daily)
NSAIDs and cyclo-oxygenase 2 inhibitors should be avoided
Potassium supplements should be discontinued or reduced
Close monitoring of serum potassium is required; potassium levels and renal function should be checked within 3 days and at 1 week after initiation of therapy and at least monthly for the first 3 months
Diarrhea or other causes of dehydration should be addressed immediately

ACC/AHA guidelines for Minimizing the Risk of Hyperkalemia in Patients Treated With Aldosterone-receptor Antagonists

^aAlthough the entry criteria for the trials of aldosterone-receptor antagonists included creatinine greater than 221.0 µmol/l (>2.5 mg/dl), the majority of patients had much lower creatinine levels; in 1 trial, 95% of patients had creatinine ?150.0 µmol/l (?1.7 mg/dl). From Hunt SA et al. (2005) ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation 112: e154-e235 Epub 2005 Sep 13, with permission.

As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

Author(s)

Srinivasa R. Kalidindi

Clinical Scholar, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio

Disclosures

Disclosure: Srinivasa R. Kalidindi has disclosed no relevant financial relationships.

W.H. Wilson Tang

Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio

Disclosures

Disclosure: W.H. Wilson Tang has disclosed associations with the following companies: AstraZeneca, GlaxoSmithKline, Novartis, and Pfizer.

Gary S. Francis, MD

Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio

Disclosures

Disclosure: Gary S. Francis has disclosed associations with the following companies: AstraZeneca, GlaxoSmithKline, Novartis, and Pfizer.

processing....

Summary and Introduction

Summary

Aldosterone is an important mediator in the pathogenesis of heart failure, and increased plasma aldosterone levels are associated with a poor prognosis. Aldosterone-receptor blocking drugs can slow the progression of left ventricular remodeling and reduce the occurrence of sudden cardiac death. Two widely publicized clinical trials provide data demonstrating survival benefits with spironolactone and eplerenone in chronic and postinfarction heart failure. The publication of these trials has generated widespread enthusiasm for spironolactone and eplerenone, leading to the more frequent and sometimes unbridled use of these drugs in the medical community. We herein describe the likely mechanisms of action of aldosterone-receptor antagonists, discuss the existing clinical evidence supporting their use, and provide practical advice on their use in the management of patients with heart failure.

Introduction

Heart failure (HF) is a chronic, progressive disease associated with high morbidity and mortality. The prevalence of the disease is fast reaching epidemic proportions, especially in Western countries. The associated economic burden is enormous; in the US alone, the estimated direct and indirect cost of HF for 2007 is US$33.2 billion.^[1] Although the use of angiotensin-converting-enzyme (ACE) inhibitors and Î²-blockers has prolonged survival of patients with HF,^[2-4] the incidence of this disease has not receded, which has in turn led to increased prevalence. Moreover, although ACE inhibitors and Î²-blockers significantly reduce mortality in patients with HF, clinical events continue to occur. The introduction of aldosterone-receptor antagonists has provided the clinician with an additional tool in the fight against HF. The use of these drugs, however, has not been without controversy. In this Review, we discuss the likely mechanisms of action of aldosterone-receptor antagonists, the existing clinical evidence supporting their use, and provide practical advice on how to use these drugs in the management of patients with HF.

Page 1 of 11

Aldosterone in Heart Failure

Summary and Introduction
Aldosterone in Heart Failure
The Rationale for Aldosterone-receptor Antagonists
Clinical Evidence
Mechanisms of Benefit With Aldosterone Receptor Antagonists
Adverse Effects
Real World Experience
Practice Recommendations
Controversies and Challenges
Conclusions
Key Points

Print
Like Tweet

Table 1.

Box 1.

Drug Insight: Aldosterone-Receptor Antagonists in Heart Failure -- The Journey Continues

Summary and Introduction

Summary

Introduction

Table of Contents

Table 1.

Box 1.

Faculty and Disclosures

Author(s)

Srinivasa R. Kalidindi

W.H. Wilson Tang

Gary S. Francis, MD

Drug Insight: Aldosterone-Receptor Antagonists in Heart Failure -- The Journey Continues

Summary and Introduction

Summary

Introduction

Table of Contents