Review Question - QID 100967

Of the given answer choices, spironolactone is the only agent shown to decrease mortality in advanced heart failure.

The RALES trial showed that spironolactone improved morbidity and mortality in patients with class III and IV congestive heart failure (CHF). Spironolactone is an aldosterone antagonist; it is believed that the benefits seen in CHF are due to spironolactone dampening aldosterone's unwanted effects. Specifically, spironolactone is thought to decrease cardiac fibrosis and ventricular remodeling under the control of aldosterone.

The RALES study (Zannad et al.) found that in patients with CHF, high baseline serum levels of markers of cardiac fibrosis synthesis were significantly associated with poor outcomes. These values decreased during spironolactone therapy, and with increased levels of collagen synthesis markers. This study suggests that limiting excessive extracellular matrix turnover may be one of the various extrarenal benefits of spironolactone, particularly in patients with CHF.

It is interesting to note that the publication of the RALES study resulted in an increased incidence of complications due to hyperkalemia, a common side effect of therapy with spironolactone. Juurlink et al. report that following the publication of RALES, there was an associated increase in the rate of prescriptions for spironolactone as well as an increase in cases of hyperkalemia-associated morbidity and mortality.

Illustration A is a table outlining the New York Heart Association (NYHA) Classification of heart failure.

Incorrect Answers:
Answers 2-5: These medications have not been shown to decrease mortality in severe congestive heart failure.