Aldosterone Antagonists in the Treatment of Heart Failure

Todd R. Marcy; Toni L. Ripley


Am J Health Syst Pharm. 2006;63(1):49-58. 

In This Article

Pharmacologic Management of Heart Failure

The pharmacologic management of heart failure focuses on several mechanisms. Aldosterone antagonism, β-blockade, and ACE inhibition have been associated with improved morbidity and mortality rates.[4,5,30,31,32] ARBs have not established superiority over ACE inhibitors in reducing morbidity or mortality in patients with heart failure.[33,34] Combination therapy with ACE inhibitors and ARBs has produced conflicting results.[34,35,36] In the absence of contraindications, all stable patients with left ventricular systolic dysfunction should receive an appropriate β-blocker (bisoprolol, carvedilol, or extended-release metoprolol succinate) plus an ACE inhibitor.[1] Digoxin improves morbidity but has no effect on mortality.[37] Diuretics are used to reduce the symptoms of fluid overload in patients with symptomatic heart failure, but available short-term studies have not shown a mortality benefit.[7]

The benefit of ACE inhibitors in heart failure has been attributed to several factors, including the reduction of angiotensin II and aldosterone levels. The effects of ACE inhibitors and ARBs on serum aldosterone values do not persist over time. Initially, serum aldosterone levels decline from baseline. However, two weeks to one month after initiating ACE inhibitors, aldosterone levels begin to normalize.[38,39,40] This phenomenon is known as "aldosterone escape" and has also been seen in patients taking combination ACE inhibitor and ARB therapy.[41] Non-ACE pathways for converting angiotensin I to angiotensin II have also been identified.[42,43] Angiotensin II derived from non-ACE pathways stimulates aldosterone production and is unaffected by ACE inhibition.