title: Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Tsukuba, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yasumura
authors.forename: Kunio
authors.initials: K
authors.lastname: Miyatake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyauchi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kawana
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsutamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takaoka
authors.forename: Teisuke
authors.initials: T
authors.lastname: Anzai
authors.forename: Hideo
authors.initials: H
authors.lastname: Himeno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokoya
authors.forename: Uichirou
authors.initials: U
authors.lastname: Shintani
authors.forename: Katsuji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Koretsune
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Katsuji
authors.initials: K
authors.lastname: Imai
authors.forename: Shingo
authors.initials: S
authors.lastname: Maruyama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Masaoka
authors.forename: Michihito
authors.initials: M
authors.lastname: Sekiya
authors.forename: Teruo
authors.initials: T
authors.lastname: Shiraki
authors.forename: Hisanori
authors.initials: H
authors.lastname: Shinohara
authors.forename: Keizaburo
authors.initials: K
authors.lastname: Ozono
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyao
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Nomura
mesh_terms: 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
chemical_list: 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