Abstract 8406: The Addition of Direct Renin Inhibitor Aliskiren to Standard Therapy Suppresses Enhanced Cardiac Sympathetic Activity in Patients with Systolic Heart Failure
Introduction: Aliskiren, direct rennin inhibitor, decreases plasma brain natriuretic peptide (BNP) concentrations in patients with heart failure (HF). However, the effect of aliskiren on cardiac sympathetic nerve function is unclear.
Hypothesis and Objectives: We examined the effects of aliskiren on neurohormonal function when added to standard therapy in patients with systolic HF, under the hypothesis that aliskiren therapy would affect sympathetic nerve function.
Methods: We enrolled 34 patients with HF due to systolic dysfunction (LVEF of <45%), receiving standard therapy including an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker and a beta-blocker. We randomly assigned 17 patients to receive additional aliskiren treatment 150 mg/d (aliskiren group), while 17 patients continued standard therapy (control group). All patients underwent neurohormonal measurements and planar 123I-metaiodobenzylguanidine (MIBG) imaging. In the MIBG images, the heart/mediastinum (H/M) ratio and cardiac washout rate (WR) were determined for evaluating cardiac sympathetic activity. The follow-up data was obtained three months later.
Results: There were no significant changes in the hemodynamics in either group. In the aliskiren group, plasma renin activity fell and concomitantly, the WR decreased and H/M ratio increased during the follow-up period (WR: 39.4 ± 13.3 % to 32.9 ± 9.2 %, p = 0.009, H/M: 2.84 ± 0.68 to 3.13 ± 0.77, p = 0.016). In addition, BNP fell from 150.7 ± 102.3 pg/mL to 99.9 ± 70.5 pg/mL (p=0.001). We found a significant negative correlation between the change in WR and the baseline PRA in the aliskiren group (r = - 0.64, p = 0.004). This correlation suggests that inhibition of the circulating renin activity might be possible mechanism for sympatho-inhibitory effects by aliskiren. In the control group, MIBG imaging findings and plasma BNP concentration remained unchanged.
Conclusions: The addition of aliskiren to standard therapy led to renin-angiotensin-aldosterone system inhibition, which subsequently led to the suppression of enhanced cardiac sympathetic activity and a decrease in plasma BNP concentrations in patients with systolic HF.
- © 2011 by American Heart Association, Inc.