Additive effects of spironolactone and candesartan on cardiac sympathetic nerve activity and left ventricular remodeling in patients with congestive heart failure.
The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine in the myocardium. However, the additive effects of combined spironolactone and candesartan on cardiac sympathetic nerve activity (CSNA) have not been determined. We investigated the effects of the angiotensin-receptor blocker candesartan alone and in combination with spironolactone on CSNA in patients with congestive heart failure (CHF).


METHODS
Fifty patients with CHF (left ventricular ejection fraction [LVEF] < 45%) were randomly assigned to candesartan plus spironolactone (group A; n = 25) or to candesartan alone (group B; n = 25). All patients were also treated with a loop diuretic. The delayed percent denervation, delayed heart-to-mediastinum count (H/M) ratio, and washout rate (WR) were determined from (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, and plasma brain natriuretic peptide (BNP) concentration was measured before and 6 mo after treatment. The LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LVEF were also determined by echocardiography.


RESULTS
After 6 mo, all of these parameters were improved in both groups. However, the degree of change in the percent denervation was -14 +/- 12 in group A and -7 +/- 10 in group B (P < 0.05); the change in the H/M ratio was 0.19 +/- 0.18 in group A and 0.08 +/- 0.14 in group B (P < 0.05), the change in WR was -12% +/- 8% in group A and -5% +/- 13% in group B (P < 0.05), and the change in plasma BNP was -100 +/- 83 pg/mL in group A and -43 +/- 97 pg/mL in group B (P < 0.05). The degree of change in LVEDV, LVESV, and LVEF in group A tended to be better than that in group B, but these changes were not statistically significant. Moreover, there were significant correlations between changes in the (123)I-MIBG scintigraphic findings and changes in the LVEDV (% denervation, r = 0.692, P < 0.001; H/M ratio, r = -0.437, P < 0.05; and WR, r = 0.505, P < 0.01) or the LVESV (% denervation, r = 0.663, P < 0.001; H/M ratio, r = -0.438, P < 0.05; and WR, r = 0.532, P < 0.01) in group A. In contrast, there was no relationship between these parameters in group B.


CONCLUSIONS
These findings indicate that the combination of spironolactone and candesartan may be more beneficial for CSNA and LV performance than candesartan alone in patients with CHF.
Kasama
Shu
S
Department of Cardiovascular Medicine, Gunma University School of Medicine, Maebashi, Japan. s-kasama@bay.wind.ne.jp
Toyama
Takuji
T
Sumino
Hiroyuki
H
Matsumoto
Naoya
N
Sato
Yuichi
Y
Kumakura
Hisao
H
Takayama
Yoshiaki
Y
Ichikawa
Shuichi
S
Suzuki
Tadashi
T
Kurabayashi
Masahiko
M
D019797:3-Iodobenzylguanidine; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D013148:Spironolactone / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D020097:Natriuretic Peptide, Brain; D013148:Spironolactone; D019797:3-Iodobenzylguanidine; C081643:candesartan