ALDOSTERONE ANTAGONISTS •SpironolactoneBlocks cytoplasmic aldosterone receptors in collecting tubules ofnephron•possiblemembrane effect Increased salt and water excretion•reducesremodeling Chronic heart failure •aldosteronism(cirrhosis,adrenal tumor) •hypertension•hasbeenshown to reduce mortality Oral•duration24–72h(slowonsetandoffset)•Toxicity: Hyperkalemia, antiandrogen actions •Eplerenone: Similar to spironolactone; more selective antimineralocorticoid effect; no significant antiandrogen action; has been shown to reduce mortality
Angiotensin-converting enzyme (ACE) inhibitors:
Angiotensin receptor blockers (ARBs): formation by inhibiting conversion of AI to AII
Enalapril, many other ACE inhibitors: Like captopril
Candesartan, valsartan, many other ARBs: Like losartan
Chronic heart failure: To slow failure • many other indications in Chapter 10 Oral • duration 10–12 h • Toxicity:
Bronchospasm, bradycardia, atrioventricular block, acute • Metoprolol, bisoprolol, nebivolol: Select group of b blockers that have been shown to reduce heart failure mortality •Digoxin(otherglycosides are used outside the USA) Na+/K+-ATPase inhibition results in reduced Ca2+ expulsion and increased Ca2+ stored in sarcoplasmic reticulum Increases cardiac contractility •cardiacparasympathomimeticeffect (slowed sinus heart rate, slowed atrioventricular conduction) Chronic symptomatic heart failure•rapidventricularrateinatrialfibrillation•hasnotbeen shown to reduce mortality but does reduce rehospitalization Oral,parenteral•duration36–40h•Toxicity: Nausea, vomiting,diarrhea•cardiacarrhythmias CARDIAC GLYCOSIDE
Enalapril Generic, Vasotec, Vasotec I.V.
Fosinopril Generic, Monopril
Lisinopril Generic, Prinivil, Zestril
Quinapril Generic, Accupril
Ramipril Generic, Altace
Trandolapril Generic, Mavik
Eprosartan Generic, Teveten
Irbesartan Generic, Avapro
Losartan Generic, Cozaar
Telmisartan Generic, Micardis
Bisoprolol Generic, Zebeta
Carvedilol Generic, Coreg
Metoprolol Generic, Lopressor, Toprol XL
Eplerenone Generic, Inspra
Isosorbide dinitrate Generic, Isordil
Milrinone Generic, Primacor
Ahmed A et al: Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. Am J Cardiol 2009;103:82.
Borlaug BA, Colucci WS: Treatment and prognosis of heart failure with preserved ejection fraction. UpToDate, 2016. http://www.UpToDate.com.
Bourge RC et al: Digoxin reduces 30-day all-cause hospital admission in older patients with chronic systolic heart failure. Am J Med 2013;126:701.
Braunwald E: Heart failure. J Am Coll Cardiol HF:Heart Failure 2013;1:1.
Cleland JCF et al: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539.
Cleland JCF et al: The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: A double blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet 2011;378:676.