Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure.
BACKGROUND
The present multicenter study investigated whether the combination of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) is more beneficial for preventing left ventricular remodeling and suppressing neurohumoral factors than either ACEI or ARB alone.


RESULTS
One hundred and six patients with mild-to-moderate congestive heart failure treated in 26 Japanese institutes were randomly assigned to the combination therapy or monotherapy. Changes in physical activity (New York Heart Association functional classes, Specific Activity Scale (SAS)), concentrations of neurohumoral factors (plasma renin activity, angiotensin II, aldosterone, and brain natriuretic peptide (BNP)), and cardiac function for 6 months were compared between the 2 groups. It was found that the combination therapy, which was administered at doses standard in Japan, increased the SAS score (4.5 +/- 1.5 to 4.9 +/- 1.5, p<0.05) and decreased the plasma BNP concentration (183 +/- 163 to 135 +/- 118 pg/ml, p<0.05). In contrast, there were no changes in SAS score (4.5 +/- 1.4 to 4.6 +/- 1.4, NS) or BNP concentration (156 +/- 157 to 151 +/- 185 pg/ml, NS) in the patients receiving monotherapy.


CONCLUSIONS
The results of the study demonstrate that the combination therapy, even at the standard doses for Japan, improves physical activity and plasma BNP concentration more than the monotherapy. A larger study is required to assess the effects of the combination therapy on major clinical outcomes.
Yasumura
Yoshio
Y
Division of Cardiology, Department of Medicine, University of Tsukuba, Japan.
Miyatake
Kunio
K
Okamoto
Hiroshi
H
Miyauchi
Takeshi
T
Kawana
Masatoshi
M
Tsutamoto
Takayoshi
T
Kitakaze
Masafumi
M
Matsubara
Hiroaki
H
Takaoka
Hideyuki
H
Anzai
Teisuke
T
Himeno
Hideo
H
Yokoyama
Hiroyuki
H
Yokoya
Koichi
K
Shintani
Uichirou
U
Hashimoto
Katsuji
K
Koretsune
Yukihiro
Y
Nakamura
Yukio
Y
Imai
Katsuji
K
Maruyama
Shingo
S
Masaoka
Yoshiko
Y
Sekiya
Michihito
M
Shiraki
Teruo
T
Shinohara
Hisanori
H
Ozono
Keizaburo
K
Matsuoka
Tatsuru
T
Miyao
Yuji
Y
Nomura
Fumikazu
F
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006334:Heart Function Tests; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011945:Receptors, Angiotensin / Q000187:drug effects*; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D000068756:Valsartan; D012083:Renin; D014633:Valine; D019808:Losartan; C081643:candesartan