Congestive heart failure aldosterone antagonists

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Acute Pharmacotherapy
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ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
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Patients at high risk for developing heart failure (Stage A)
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Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

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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] Edzel Lorraine Co, DMD, MD[4]

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.[1][2]

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%[3]

and

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

Background

  • Members of this class in clinical use include: Spironolactone[5]; Eplerenone[6][3] - 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.

Dosing

Aldosterone antagonist Starting dose Target dose
Spirinolactone 25 mg QD 50 mg QD
Eplerenone 25 mg b.i.d. 50 mg QD

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.

2022 AHA/ACC/HFSA Heart Failure Guideline/ 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure/2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline,2013 ACC/AHA Guideline, 2009 ACC/AHA Focused Update and 2005 Guidelines for the Diagnosis and Management of Heart Failure in the Adult (DO NOT EDIT) [7][8][9]

Renin-Angiotensin System Inhibition With ACEi or ARB or ARNi

Class I
"1. In patients with HFrEF and NYHA class II to III symptoms, the use of ARNi is recommended to reduce morbidity and mortality. [10][11][12][13][14](Level of Evidence: A) "
"2. In patients with previous or current symptoms of chronic HFrEF, the use of ACEi is beneficial to reduce morbidity and mortality when the use of ARNi is not feasible.[15][16][17][18][19][20][21][22] (Level of Evidence: A) "
"3. In patients with previous or current symptoms of chronic HFrEF who are intolerant to ACEi because of cough or angioedema and when the use of ARNi is not feasible, the use of ARB is recommended to reduce morbidity and mortality. [23][24][25][26][27] (Level of Evidence: A) "
"5. In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACEi or ARB, replacement by an ARNi is recommended to further reduce morbidity and mortality. [10][11][12][13][14](Level of Evidence: B-R) "
Class Value Statement: High Value
"4. In patients with previous or current symptoms of chronic HFrEF, in whom ARNi is not feasible, treatment with an ACEi or ARB provides high economic value. [28][29][30][31][32][33][34](Level of Evidence: A) "
"6. In patients with chronic symptomatic HFrEF, treatment with an ARNi instead of an ACEi provides high economic value. [35][36][37][38] (Level of Evidence: A) "
Class III (Harm)
"7. ARNi should not be administered concomitantly with ACEi or within 36 hours of the last dose of an ACEi. [39][40] (Level of Evidence: B-R) "
"8. ARNi should not be administered to patients with any history of angioedema.[41][42][43][44] (Level of Evidence: C-LD) "
"9. ACEi should not be administered to patients with any history of angioedema. [45][46][47][48] (Level of Evidence: C-LD) "

Vote on and Suggest Revisions to the Current Guidelines

External Links

References

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