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PHARMACOLOGICAL TREATMENT OF HEART FAILURE (HF) - page 38 / 48

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prognostic effects in experimental models of HF. Two types of endothelin-1 antagonists are under evaluation: those that block the receptors for endothelin-1, and those that inhibit the endothelin converting-enzyme, which is responsible for the formation of endothelin-1. In two small pilot studies, high doses of the endothelin receptor antagonist bosentan produced favorable effects on cardiac performance and clinical status, but were associated with liver-function abnormalities. In another recently completed trial, treatment with the endothelin antagonist enrasentan was associated with no improvement in symptoms and an increased risk of worsening HF. The utility of low doses of bosentan is now being evaluated in a large-scale trial. No endothelin antagonist is presently available for clinical use for any indication.

In summary, the following are the AHA/ACC guidelines for patients with HF in stage C:

Class I recommendations

Measures listed as Class I recommendations for patients in stages A and B are also appropriate for patients in Stage C. (Levels of Evidence: A, B, and C as appropriate)

Diuretics and salt restriction are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention. (Level of Evidence: C)

Angiotensin converting enzyme inhibitors are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated (Level of Evidence: A)

Beta-blockers (using 1 of the 3 proven to reduce mortality, ie. bisoprolol, carvedilol, and sustained release metoprolol succinate) are recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. (Level of Evidence: A)

Angiotensin II receptor blockers approved for the treatment of HF are recommended in patients with current or prior symptoms of HF and reduced LVEF who are ACEI intolerant (Level of Evidence: A)

Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HF and reduced LVEF should be avoided or withdrawn whenever possible (e.g., nonsteroidal anti-inflammatory drugs, most antiarrhythmic drugs, and most calcium channel blocking drugs; see text). (Level of Evidence: B)

Addition of an aldosterone antagonist is reasonable in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be less than or equal to 2.5 mg/dL in men or less

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