Congestive heart failure aldosterone antagonists

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Editor(s)-In-Chief: James Chang, M.D., Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School [1] and C. Michael Gibson, M.S., M.D. [2], Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [3]

Overview

Aldosterone has been proved to play a significant role in the pathophysiology of congestive heart failure (CHF). Poor perfusion leads to activation of renin-angiotensin system which in turn elevates the levels of aldosterone. Aldosterone causes abnormal sodium retention in the body causing further progression of CHF. The RALES (Randomized Aldactone Evaluation Study) trial showed early reduction in morbidity and mortality using spironolactone, an aldosterone antagonist, in combination with ACE inhibitors and loop diuretics in patients with congested heart failure.

Aldosterone Antagonists

Indications for Aldosterone Antagonists Use

A patient should be on an aldosterone antagonist if:

1. The potassium (K) is ≤ 5.0 mmol/liter

and

2. The creatinine (Cr) is ≤ 2.5 mg/dl

and

3. The left ventricular ejection fraction (LVEF) is ≤ 35%

OR

1. The potassium (K) is ≤ 5.0 mmol/liter

and

2. The creatinine (Cr) is ≤ 2.5 mg/dl

and

3. The left ventricular ejection fraction (LVEF is ≤ 40%

and

4. There is a history of prior myocardial infarction (MI)

Background

• Aldosterone antagonists are, as the name suggests, receptor antagonists at the mineralocorticoid receptor. Antagonism of these receptors inhibits sodium resorption in the collecting duct of the nephron in the kidneys. This interferes with sodium/potassium exchange, reducing urinary potassium excretion and weakly increasing water excretion (diuresis).

• Members of this class in clinical use include: Spironolactone; Eplerenone - more specific than spironolactone on target, but also more expensive; and Canrenone (canrenoate potassium)
• Aldosterone antagonist therapy is recommended for patients with advanced heart failure (NYHA class III or IV) and left ventricular systolic dysfunction (LVEF ≤ 35%), who are already receiving optimal medical therapy including loop diuretics, beta blockers and ACE-I/ARBs.
• In patients with diabetes mellitus or prior myocardial infarction, the LVEF below which this recommendation applies is 40%.
• In addition, the EMPHASIS-HF trial showed that eplerenone at a dose of 25-50mg daily reduced mortality and HF hospitalizations in patients with NYHA class I or II HF and should now be considered in these patients. This is not yet an AHA guideline but should be considered in this group of patients based on the available evidence.

Contraindications

• However, patients with baseline renal insufficiency (creatinine > 2.5 mg/dl or creatinine clearance < 30 ml/min), hyperkalemia (K > 5.0 mmol/liter), or who are unlikely to be available for frequent monitoring of renal function and electrolytes should NOT receive an aldosterone antagonist. Other potassium-sparing diuretics (such as triamterene) should not be administered concomitantly with an aldosterone antagonist.

2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America

Aldosterone Antagonists in Patients Presenting With Heart Failure (DO NOT EDIT)

Class I

1. The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors (Level of Evidence: A), OR ARBs (Level of Evidence: A), OR ARNI (Level of Evidence: B-R) in conjunction with evidence-based beta blockers, and aldosterone antagonists in selected patients, is recommended for patients with chronic HFrEF to reduce morbidity and mortality. (Class I, Level of Evidence: A)

"2. Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of heart failure and reduced left ventricular ejection fraction (LVEF) who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be 2.5 mg per dL or less in men or 2.0 mg per dL or less in women and potassium should be less than 5.0 mEq per liter. Under circumstances where monitoring for hyperkalemia or renal dysfunction is not anticipated to be feasible, the risks may outweigh the benefits of aldosterone antagonists. (Level of Evidence: B) "

Class III (No Benefit)

"1. Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (LVEF). (Level of Evidence: C) "

Class IIb

1. In appropriately selected patients with HFpEF (with EF ≥ 45%, elevated BNP levels or HF admission within 1 year, estimated glomerular filtration rate >30 mL/min, creatinine <2.5 mg/dL, potassium <5.0 mEq/L), aldosterone receptor antagonists might be considered to decrease hospitalizations. (Class IIb, Level of Evidence: B-R)

2. The use of ARBs might be considered to decrease hospitalizations for patients with HFpEF. (Class IIb, Level of Evidence: B)

Minimizing the Risk of Hyperkalemia in Patients Treated with Aldosterone Antagonists

“

Impaired renal function is a risk factor for hyperkalemia during treatment with aldosterone antagonists. The risk of hyperkalemia increases progressively when serum creatinine exceeds 1.6 mg per dl. In elderly patients or others with low muscle mass in whom serum creatinine does not accurately reflect glomerular filtration rate, determination that glomerular filtration rate or creatinine clearance exceeds 30 ml per min is recommended. Aldosterone antagonists should not be administered to patients with baseline serum potassium in excess of 5.0 mEq per liter. An initial dose of spironolactone 12.5 mg or eplerenone 25 mg is recommended, after which the dose may be increased to spironolactone 25 mg or eplerenone 50 mg if appropriate. The risk of hyperkalemia is increased with concomitant use of higher doses of ACEIs (captopril greater than or equal to 75 mg daily; enalapril or lisinopril greater than or equal to 10 mg daily). Nonsteroidal anti-inflammatory drugs 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 in 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 emergently.

”

Vote on and Suggest Revisions to the Current Guidelines

• The CHF Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines

External Links

• The ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult

• 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation

References

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