Key result
Spironolactone reduces plasma BNP ~23% compared with placebo.
Why the study?
Although spironolactone significantly reduced mortality in patients with severe CHF in the RALES trial, its mechanism of action and neurohormonal impact remained to be clarified.
Does spironolactone modify plasma concentrations of neurohormonal factors (N-proANF, BNP, ET-1, NE, AII, and aldosterone) in patients with severe congestive heart failure?
RCT (n=107)
Placebo-controlled
Subgroup of the Randomized ALdactone Evaluation Study (RALES)
Does spironolactone modify plasma concentrations of neurohormonal factors (N-proANF, BNP, ET-1, NE, AII, and aldosterone) in patients with severe congestive heart failure?
Answers are grounded in this paper and cite their sources.
In patients with severe congestive heart failure, spironolactone reduces circulating natriuretic peptides (BNP and N-proANF) while increasing angiotensin II and aldosterone levels, suggesting improved left ventricular diastolic filling pressures alongside activated neurohormonal feedback mechanisms.
Objectives We sought to evaluate the effects of spironolactone on neurohormonal factors in patients with severe congestive heart failure (CHF). Background In the Randomized ALdactone Evaluation Study (RALES), spironolactone, an aldosterone receptor antagonist, significantly reduced mortality in patients with severe CHF. However, the mechanism of action and neurohormonal impact of this therapy remain to be clarified. Methods The effects of spironolactone (25 mg/day; n = 54) or placebo (n = 53) on plasma concentrations of the N-terminal portion of atrial natriuretic factor (N-proANF), brain natriuretic peptide (BNP), endothelin-1 (ET-1), norepinephrine (NE), angiotensin II (AII), and aldosterone were assessed in a subgroup of 107 patients (New York Heart Association functional class III to IV; mean ejection fraction 25%) at study entry and at three and six months. Results Compared with the placebo group, plasma levels of BNP (-23% at 3 and 6 months; p = 0.004 and p = 0.05, respectively) and N-proANF (-19% at 3 months, p = 0.03; -16% at 6 months, p = 0.11) were decreased after spironolactone treatment. Over time, spironolactone did not modify the plasma levels of NE and ET-1. Angiotensin II increased significantly in the spironolactone group at three and six months (p = 0.003 and p = 0.001, respectively). As expected, a significant increase in aldosterone levels was observed over time in the spironolactone group (p = 0.001). Conclusions Spironolactone administration in patients with CHF has opposite effects on circulating levels of natriuretic peptides (which decrease) and aldosterone and AII (which increase). The reduction in natriuretic peptides might be related to changes in left ventricular diastolic filling pressure and/or compliance, whereas the increase in AII and aldosterone probably reflects activated feedback mechanisms. Further studies are needed to link these changes to the beneficial effects on survival and to determine whether the addition of an AII antagonist could be useful in this setting.
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Rousseau et al. (2002) conducted an RCT in Severe congestive heart failure (CHF) (n=107). Spironolactone vs. Placebo was evaluated on Plasma concentrations of neurohormonal factors (N-proANF, BNP, ET-1, NE, AII, and aldosterone) at 3 and 6 months (p=0.004 at 3 months; 0.05 at 6 months (for BNP)). Spironolactone decreased plasma BNP and increased angiotensin II and aldosterone compared with placebo.
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