High-dose spironolactone changes renin and aldosterone levels in acutely decompensated heart failure

Abstract

c o r e t v a s a 5 6 ( 2 0 1 4 ) e 4 6 3 -e 4 7 0 antagonism Renin Aldosterone Acute heart failure a b s t r a c t Background: In acutely decompensated heart failure (ADHF) patients with higher aldosterone levels correlate with worse postdischarge outcomes, suggesting that further modulation of the mineralocorticoid system during or immediately after hospitalization might favorably improve outcomes. Methods and results: This was an observational, retrospective secondary analysis of a study including 100 patients with ADHF. In that study 50 patients were submitted to spironolactone treatment (50-100 mg/day). A higher proportion of patients with renin levels above 16.5 pg/mL and aldosterone levels above 100 ng/dL were observed in subjects submitted to spironolactone treatment (44.7% vs. 66.7% and 56% vs. 64.7%, respectively, both p < 0.05). In the group of patients submitted to spironolactone treatment the proportion of patients with renin and aldosterone levels above the cutoff had a significant increase from baseline to day 3 (24-32% and 16-44%, respectively, both p < 0.05). Log renin and aldosterone were higher in patients with renin and aldosterone levels above the cutoff point (both p < 0.05). Conclusions: High-dose spironolactone added to standard ADHF therapy induces an additional increase in renin and aldosterone levels. Whether higher levels of renin and aldosterone due to the reactive response to full MRA still have prognostic value requires further investigation.

Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure

“…Moreover, the current analysis also showed the association of higher doses of ACEi/ARB with lower aldosterone, suggesting that despite the aldosterone ‘escape’ phenomenon, a chronic decrease of aldosterone levels in patients taking ACEi/ARB therapy may occur. On the other hand, increased renin and aldosterone levels in patients treated with MRAs are consistent with previous reports . This is likely related to an increase in angiotensin II via feedback mechanisms of the RAAS cascade or by direct regulation of aldosterone synthase by MRA treatment .…”

Geographic differences in heart failure trials

“…This study provided very useful information on patient compliance, which is underestimated by clinical methods and study protocols. In the setting of MRA use, a plausible, yet challenging method to assess compliance may be to determine the urinary sodium to potassium ratio and/or serum aldosterone at different time points, since they have been shown to be potential surrogate markers of MRA therapy . Simple ‘pharmacological’ adverse events such as hyperkalaemia can help ascertain compliance in renin–angiotensin–aldosterone system (RAAS) inhibitor therapy such as secondarily reported in TOPCAT.…”

Mineralocorticoid Receptor Antagonists Eplerenone and Spironolactone Modify Adrenal Cortex Morphology and Physiology

“…Unfortunately, due to limited plasma volume derived from the use of a small rodent in the experiments, it was not possible to measure renin activity and angiotensin II levels to confirm this. Nevertheless, previous data supports this hypothesis since aldosterone receptor blockade with both MRAs drugs, eplerenone and spironolactone, has previously been shown to increase renin activity, angiotensin II and aldosterone levels in hypertensive rats and humans [ 34 , 35 , 36 , 37 ]. In addition, our study further suggests that the MRAs effects on the aldosterone production are independent of a direct action on the steroidogenesis pathway, since no differences in the expression of proteins involved in this process were observed.…”

“…However, it should be noticed that in vitro studies lack the involvement of other key players in aldosterone production, such as the RAAS. From the present literature, it is clear that the RAAS must have a major role, as in the present in vivo experiments and can counteract any direct inhibitory action of the MRAs, leading instead to elevated aldosterone levels [ 35 , 37 ]. In contrast, in vitro studies indicate that eplerenone had no effect on either aldosterone or cortisol production [ 16 ].…”