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Circ J. 2004 Apr;68(4):361-6.

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

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Division of Cardiology, Department of Medicine, University of Tsukuba, Japan.



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.


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.


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.

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