Heart Failure


Aldosterone Antagonists

  • BENEFIT OF THERAPY:
    • decrease morbidity, mortality, and hospitalizations
  • PLACE IN THERAPY:
    • Recommended for ALL patients who are already taking recommended therapies, including beta-blockers, ACEI (or ARB), and diuretics, AND who have NYHA class III or IV heart failure due to LV systolic dysfunction (LVEF 35% or less)
    • Consider addition of aldosterone antagonist in patients post-MI with heart failure or diabetes and an LVEF < 40% who are taking recommended therapies, including an angiotensin converting enzyme (ACE) inhibitor or an alodosterone receptor blocker (ARB)

Spironolactone
Eplerenone
Product name and appearance
Aldactone and various generic products
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Spironolactone tablets

Spironolactone tablets
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Inspra 25mg tablets


Inspra 25mg tablets



Inspra (Not available as a generic product yet - Sept 2009)





FDA Approved Indication
severe heart failure to increase survival and reduce hospitalization when added to ACE inhibitor and loop diuretic +/- digoxin
Heart failure post-MI
Dosing Considerations
Initial: 12.5-25 mg/day ORALLY
Max daily dose: 50 mg ORALLY
If 25 mg once daily not tolerated, reduce to 25 mg every other day

Note: If potassium >5 mEq/L or serum creatinine >4 mg/dL, discontinue or interrupt therapy.

Renal impairment:

  • Clcr 31-50 mL/min: Decrease initial dose to 12.5 mg once daily.
  • Clcr < 30 mL/min: Not recommended
Initial: 25 mg ORALLY once daily
Titration: preferably within 4 weeks, increase to 50 mg ORALLY once daily

Dosage adjustment per K concentrations:
  • < 5.0 mEq/L:
    Increase dose from 25 mg every other day to 25 mg daily or Increase dose from 25 mg daily to 50 mg daily
  • 5.0-5.4 mEq/L: No adjustment needed
  • 5.5-5.9 mEq/L: Decrease dose from 50 mg daily to 25 mg daily or Decrease dose from 25 mg daily to 25 mg every other day or Decrease dose from 25 mg every other day to withhold medication
  • ≥ 6.0 mEq/L: Withhold medication until potassium <5.5 mEq/L, then restart at 25 mg every other day



Contraindications
  • anuria
  • hyperkalemia
  • acute renal insufficiency
  • significant renal excretory function impairment
  • CrCl of 30 mL/min or less
  • serum potassium greater than 5.5 mEq/L at initiation
  • concomitant use with strong CYP3A4 inhibitors
    • i.e. clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin

  • Aldosterone antagonists are NOT RECOMMENDED when:
    • SCr > 2.5 mg/dL or CrCl < 30 mL/min
    • serum K > 5.0 mmol/L
    • patient is using other potassium-sparing diuretics (i.e. amiloride, triamterene)
    • supplemental K NOT RECOMMENDED unless K < 4.0 mmol/L


Helpful Resources

  • Spironolactone. (n.d.) DRUGDEX® System. Retrieved August 30, 2009, from http://www.thomsonhc.com. Greenwood Village, CO : Thomson Healthcare.
  • Spironolactone. Lexi-Comp Online®. Hudson, Ohio: Lexi-Comp, Inc.; 2009; February 10, 2010.
  • Eplerenone. (n.d.) DRUGDEX® System. Retrieved August 30, 2009, from http://www.thomsonhc.com. Greenwood Village, CO : Thomson Healthcare.
  • Eplerenone. Lexi-Comp Online®. Hudson, Ohio: Lexi-Comp, Inc.; 2009; February 10, 2010.
  • Hunt SA, et al. "2009 Focused Update Incorporated Into the ACC/AHA 2005 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." Circulation. 2009;119;e391-e479.
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updated guidelines 2009.pdf
  • Pitt B, et al. "The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure." N Engl J Med. 1999;341:709-719.
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RALES - NEJM.pdf
  • Pitt B, et al. "Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction." N Eng J Med. 2003;348:1309-1321.
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EPHESUS - NEJM.pdf