Aldosterone-Receptor Blocking Agents

Abstract

Study findings pertaining to aldosterone-receptor blocking agents hold important implications in the care of patients with congestive heart failure (CHF). Such research is critical to the cardiovascular care of the postmenopausal population. Since its discovery in 1954, the hormone aldosterone has been a target for therapy in CHF because of its role in sodium retention and potassium excretion [1]. However, it is now clear that aldosterone is responsible for a wide array of adverse effects that contribute to the manifestation of CHF, including myocardial fibrosis, direct vascular damage, endothelial cell and baroreceptor dysfunction, and ventricular arrhythmias [1 – 6]. To control the production of aldosterone and thereby counter these effects, inhibition of angiotensin II, the peptide hormone responsible for the production and release of aldosterone, with an angiotensin-converting enzyme (ACE) inhibitor is standard treatment, based on the assumption that suppressing angiotensin II production will, in turn, suppress aldosterone production. However, increasing evidence suggests that ACE inhibitors cannot sustain suppression of aldosterone production [5,7 – 10], even when combined with an angiotensin-receptor blocking agent [11]. In the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study, the ACE inhibitor enalapril combined with the angiotensin receptor blocking agent candesartin in heart failure patients produced a transient reduction in serum aldosterone levels at 17 weeks. By 43 weeks, however, aldosterone levels had risen above control (Figure 1) [11].