Spirolactone in Mgmt of Congestive Heart Failure
Spirolactone in Mgmt of Congestive Heart Failure
Although there have been advances in the management of cardiovascular disease in the U.S., congestive heart failure (CHF) remains a significant public health problem. Approximately 400,000- 700,000 new cases are diagnosed each year, with 250,000 deaths and one million hospitalizations per year reported. Annual direct costs for CHF are estimated at $10-$38 billion.
CHF results when the heart is unable to meet the metabolic needs of the body. Measures that are adaptive in the presence of normal cardiac function become maladaptive in patients with CHF (Fig. 1). Increased neurohormonal activity attempts to reverse or normalize the adverse hemodynamic profile and symptoms observed in patients with CHF. Such activity is evidenced by increases in norepinephrine levels, activation and increased activity of the renin-angiotensin-aldosterone (RAA) system, release of arginine vasopressin (ADH), secretion of atrial naturetic peptide (ANP) and brain naturetic peptide (BNP), and the influence of various endothelial hormones (e.g., prostacyclin, nitric oxide).
(Enlarge Image)
Pathophysiology of congestive heart failure.
Alterations in the RAA system or axis result in the accumulation of plasma renin, angiotensin, and aldosterone. Aldosterone specifically may be responsible for promoting sodium retention, magnesium and potassium loss, sympathetic nervous system activation, parasympathetic inhibition, myocardial and vascular fibrosis, baroreceptor dysfunction, vascular damage, and impaired arterial compliance. Inhibited angiotensin II and aldosterone production has been the intended goal for using ACE inhibitors in the management of CHF, and these agents have become an important pharmacologic strategy. It is now recognized, however, that some patients "escape" the initial decrease in angiotensin I conversion to angiotensin II and aldosterone synthesis. Production of angiotensin and aldosterone via non-ACE-dependent pathways, as well as extra-adrenal production of aldosterone, have been recognized. These observations have prompted investigators to evaluate the use of spironolactone (Aldactone®), an aldosterone antagonist, as an adjunctive therapy for CHF.
Spironolactone has been available for years and has been used primarily as a diuretic. It is a relatively weak diuretic in patients with normal renin; however, in patients who have edema associated with either increased production or decreased elimination of renin (and subsequent increases in angiotensin and aldosterone), it may be much more effective. CHF is one condition associated with a profile of increased renin, angiotensin, and aldosterone, as previously discussed.
Clinicians have been reluctant to use spironolactone in the management of CHF, particularly in patients receiving concomitant ACE inhibitors, primarily because of the risk for further increases in serum potassium. The effect of spironolactone has recently been evaluated in patients with severe heart failure in the Randomized Aldactone Evaluation Study (RALES).
Although there have been advances in the management of cardiovascular disease in the U.S., congestive heart failure (CHF) remains a significant public health problem. Approximately 400,000- 700,000 new cases are diagnosed each year, with 250,000 deaths and one million hospitalizations per year reported. Annual direct costs for CHF are estimated at $10-$38 billion.
CHF results when the heart is unable to meet the metabolic needs of the body. Measures that are adaptive in the presence of normal cardiac function become maladaptive in patients with CHF (Fig. 1). Increased neurohormonal activity attempts to reverse or normalize the adverse hemodynamic profile and symptoms observed in patients with CHF. Such activity is evidenced by increases in norepinephrine levels, activation and increased activity of the renin-angiotensin-aldosterone (RAA) system, release of arginine vasopressin (ADH), secretion of atrial naturetic peptide (ANP) and brain naturetic peptide (BNP), and the influence of various endothelial hormones (e.g., prostacyclin, nitric oxide).
(Enlarge Image)
Pathophysiology of congestive heart failure.
Alterations in the RAA system or axis result in the accumulation of plasma renin, angiotensin, and aldosterone. Aldosterone specifically may be responsible for promoting sodium retention, magnesium and potassium loss, sympathetic nervous system activation, parasympathetic inhibition, myocardial and vascular fibrosis, baroreceptor dysfunction, vascular damage, and impaired arterial compliance. Inhibited angiotensin II and aldosterone production has been the intended goal for using ACE inhibitors in the management of CHF, and these agents have become an important pharmacologic strategy. It is now recognized, however, that some patients "escape" the initial decrease in angiotensin I conversion to angiotensin II and aldosterone synthesis. Production of angiotensin and aldosterone via non-ACE-dependent pathways, as well as extra-adrenal production of aldosterone, have been recognized. These observations have prompted investigators to evaluate the use of spironolactone (Aldactone®), an aldosterone antagonist, as an adjunctive therapy for CHF.
Spironolactone has been available for years and has been used primarily as a diuretic. It is a relatively weak diuretic in patients with normal renin; however, in patients who have edema associated with either increased production or decreased elimination of renin (and subsequent increases in angiotensin and aldosterone), it may be much more effective. CHF is one condition associated with a profile of increased renin, angiotensin, and aldosterone, as previously discussed.
Clinicians have been reluctant to use spironolactone in the management of CHF, particularly in patients receiving concomitant ACE inhibitors, primarily because of the risk for further increases in serum potassium. The effect of spironolactone has recently been evaluated in patients with severe heart failure in the Randomized Aldactone Evaluation Study (RALES).
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