Inhibition of the renin-angiotensin system reduces the rise in serum aldosterone
in acute coronary syndrome patients with preserved left ventricular function:
observations from the AVANT GARDE-TIMI 43 trial.
Author(s): Udell JA(1), Morrow DA, Braunwald E, Swedberg K, Bode C, Rifai N, Brunel PC,
Prescott MF, Ren F, Hoffman EB, Scirica BM.
Affiliation(s): Author information:
(1)TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and
Women's Hospital, Boston, MA 02115, USA.
Publication date & source: 2013, Clin Chem. , 59(6):959-67
BACKGROUND: Acute coronary syndrome (ACS) activates neurohormonal pathways,
including elevations in circulating aldosterone, with deleterious cardiovascular
effects. We aimed to determine if early, more complete
renin-angiotensin-aldosterone system inhibition (RAASI) in post-ACS patients
without ventricular dysfunction or heart failure would result in a graded
reduction in aldosterone concentrations.
METHODS: We performed serial measurement of serum aldosterone within the
Aliskiren and Valsartan to Reduce NT-proBNP via
Renin-Angiotensin-Aldosterone-System Blockade (AVANT GARDE)-Thrombolysis in
Myocardial Infarction (TIMI) 43 trial, a randomized double-blind, placebo
controlled trial of RAASI by valsartan, aliskiren, or both in post-ACS patients
with preserved ventricular function but increased natriuretic peptides.
Aldosterone was measured at randomization and week 8.
RESULTS: Median aldosterone concentrations were comparable across treatment arms
at baseline (9.26 ng/dL; interquartile range 7.12-12.76; n = 1073). In the
placebo group, there was a significant increase in aldosterone over 8 weeks
(19.7% rise, 2.20 (0.36) ng/dL, P < 0.0001) that was significantly reduced across
active RAASI therapies (1.36 (0.39) ng/dL with aliskiren; 1.02 (0.37) ng/dL with
valsartan; and 0.85 (0.37) ng/dL with combination therapy, P trend = 0.008).
Compared to placebo, RAASI monotherapy resulted in a pooled relative absolute
aldosterone change of -1.01 (0.45) ng/dL (P = 0.026 vs placebo), and combination
therapy resulted in a relative absolute aldosterone change of -1.35 (0.52) ng/dL
(P = 0.01 vs placebo). No significant difference in aldosterone concentrations
was achieved between dual vs single RAASI (P = 0.47).
CONCLUSIONS: In ACS patients with preserved ventricular function but increased
natriuretic peptides, serum aldosterone rises over time and is blunted by more
complete RAASI. The clinical implications and role for RAASI in this population
warrant further investigation.
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