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Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure.

AbstractBACKGROUND:
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.
METHODS AND 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.
AuthorsYoshio Yasumura, Kunio Miyatake, Hiroshi Okamoto, Takeshi Miyauchi, Masatoshi Kawana, Takayoshi Tsutamoto, Masafumi Kitakaze, Hiroaki Matsubara, Hideyuki Takaoka, Teisuke Anzai, Hideo Himeno, Hiroyuki Yokoyama, Koichi Yokoya, Uichirou Shintani, Katsuji Hashimoto, Yukihiro Koretsune, Yukio Nakamura, Katsuji Imai, Shingo Maruyama, Yoshiko Masaoka, Michihito Sekiya, Teruo Shiraki, Hisanori Shinohara, Keizaburo Ozono, Tatsuru Matsuoka, Yuji Miyao, Fumikazu Nomura
JournalCirculation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 68 Issue 4 Pg. 361-6 (Apr 2004) ISSN: 1346-9843 [Print] Japan
PMID15056835 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Biphenyl Compounds
  • Receptors, Angiotensin
  • Tetrazoles
  • Angiotensin II
  • Natriuretic Peptide, Brain
  • Aldosterone
  • Valsartan
  • Renin
  • Valine
  • Losartan
  • candesartan
Topics
  • Adrenergic beta-Antagonists (administration & dosage, pharmacology, therapeutic use)
  • Adult
  • Aged
  • Aldosterone (blood)
  • Angiotensin II (blood)
  • Angiotensin-Converting Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
  • Benzimidazoles (administration & dosage, pharmacology, therapeutic use)
  • Biphenyl Compounds
  • Drug Synergism
  • Drug Therapy, Combination
  • Exercise Tolerance (drug effects)
  • Female
  • Heart Failure (blood, drug therapy)
  • Heart Function Tests
  • Humans
  • Losartan (administration & dosage, pharmacology, therapeutic use)
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain (blood)
  • Receptors, Angiotensin (drug effects)
  • Renin (blood)
  • Tetrazoles (administration & dosage, pharmacology, therapeutic use)
  • Valine (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
  • Valsartan

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