Congestive heart failure ACE inhibitors

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Chronic Pharmacotherapy in HFrEF Diuretics ACE Inhibitors Angiotensin receptor blockers Aldosterone Antagonists Beta Blockers Ca Channel Blockers Nitrates Hydralazine Positive Inotropics Anticoagulants Angiotensin Receptor-Neprilysin Inhibitor Antiarrhythmic Drugs Nutritional Supplements Hormonal Therapies Drugs to Avoid Drug Interactions Treatment of underlying causes Associated conditions
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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

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 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%. 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.

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.

• Spironolactone is third line therapy for CHF
• An important side effect of spironolactone is hyperkalemia

References

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