Congestive heart failure ACE inhibitors

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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

Overview

The Collaborative Group on ACE Inhibitor Trials demonstrated significant reduction in total mortality and hospitalization with the administration of ACEIs that was consistent among wide range of patients.

Indications for an ACE Inhibitor or ARB

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

or

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

Background

• ACE-I or ARB therapy is recommended for ANY patient with reduced left ventricular ejection fraction (≤ 40%) regardless of the etiology of left ventricular systolic dysfunction (ischemic or nonischemic) or presence/absence of symptoms. Patients with or without heart failure (in other words, even those with asymptomatic left ventricular systolic dysfunction) are included in this recommendation.
• In addition, ACE-I/ARB therapy is indicated for patients with history of myocardial infarction whether or not left ventricular systolic dysfunction or heart failure is present.
• ACE-I or ARB therapy is also recommended for patients who are at high risk for the development of heart failure due to the presence of coronary, cerebrovascular, or peripheral vascular disease.
• Treatment should not be deferred in patients with few or no symptoms because of the significant mortality benefit derived from ACEI therapy.

Dosing

• ACE-I/ARB therapy should be initiated at low dosage such as 12.5 mg tid of captopril, 2.5 mg bid of enalapril, or 2.5 mg daily lisinopril.
• Every 4 to 6 weeks the dose is gradually uptitrated, as tolerated, toward target dosages of 20-40 mg daily for lisinopril, 10-20 mg twice daily for enalapril maleate, and 50-100 mg three times a day for captopril, or to the maximum tolerated dosage.
• ACE inhibitors are rarely adequate for the treatment of congestion without the use of diuretics.

Complications of ACE Inhibitors

• 5-10 % patients cannot tolerate ACE inhibitors because of cough. Cough can be a sign of elevated left-sided filling pressures or a side effect of ACE inhibitors due to excess bradykinin.
• ARBs are reserved for patients who are intolerant of ACE-Is for reasons (such as persistent cough) OTHER than hyperkalemia, progression of chronic kidney disease/worsening azotemia, or hypotension caused by prior ACE-I therapy. If a patient experiences hyperkalemia, worsening azotemia, or hypotension as a result of ACE-I therapy, the same is likely to result from ARB therapy. In the CHARM study candesartan reduced both hospitalization and mortality.
• Renal artery stenosis should be considered if there's a decline in renal function with the initiation of ACE inhibitors.

Indications for Aldosterone Antagonists

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.

References

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