title: 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.
abstract: 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.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Udell
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Brunel
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Prescott
authors.forename: Fang
authors.initials: F
authors.lastname: Ren
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Hoffman
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood*; D000450:Aldosterone / Q000097:blood* / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005650:Fumarates / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D005650:Fumarates; D013777:Tetrazoles; D000450:Aldosterone; C446481:aliskiren; D000068756:Valsartan; D014633:Valine