Abstract 10454: Inhibition of Renin-Angiotensin System (RAS) Reduces the Rise in Plasma Aldosterone Levels After Acute Coronary Syndromes in Patients with Preserved Left Ventricular Function: Insight From AVANT GARDE-TIMI 43 Trial
Background: Elevated aldosterone (aldo) levels after ACS are associated with adverse CV outcomes. Little is known regarding the temporal pattern of aldo levels or the influence of renin-angiotensin (RAS) inhibitors in patients post-ACS with preserved ejection fraction (pEF).
Methods: We performed serial measurement of aldo within AVANT GARDE-TIMI 43, a randomized double-blind, placebo-controlled trial of RAS inhibition by either an angiotensin receptor blocker (valsartan), renin-inhibitor (aliskiren), or their combination in 1101 post-ACS patients with preserved pEF but elevated natriuretic peptides (NP) 3 to 10 days after presentation. The primary endpoint of this pre-specified analysis was the change in aldo from baseline to Week 8.
Results: Mean (geometric) plasma aldo at baseline was (N = 1085, 263.1 pmol/L [95% CI 255.3 - 271.3]). Mean age was 63 years, one-third were women, and the index diagnosis was STEMI (59%), NSTEMI (28%) and UA (13%). Aldo increased significantly from baseline to Week 8 in the placebo group (23% rise, p=<0.0001, Figure). Notably, RAS inhibition significantly reduced the rise in aldo across therapies compared to placebo (12% rise with aliskiren; 10% rise with valsartan; and 6% rise with combination therapy [p <0.01 for each treatment compared to placebo]). Multivariable linear mixed effects modeling incorporating time, treatment, age, gender, region, index diagnosis, renal function, B-blocker use, prior RAS inhibition, DM, BNP and plasma renin activity, determined that randomized treatment (p=0.0027) was a significant predictor of aldo levels at Week 8.
Conclusion: Among patients with ACS and pEF but elevated NP, treatment with RAS inhibitors significantly ameliorated an observed natural rise in aldo levels in the first 8 weeks post-ACS. These findings are intriguing with respect to the clinical implications and potential role for inhibition of RAS in this population and warrant further investigation.
- © 2011 by American Heart Association, Inc.