Abstract | OBJECTIVES: BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor) epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.
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Authors | D J van Veldhuisen, S Genth-Zotz, J Brouwer, F Boomsma, T Netzer, A J Man In 'T Veld, Y M Pinto, K I Lie, H J Crijns |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 32
Issue 7
Pg. 1811-8
(Dec 1998)
ISSN: 0735-1097 [Print] United States |
PMID | 9857856
(Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin-Converting Enzyme Inhibitors
- Imidazoles
- Imidazolidines
- Natriuretic Peptide, Brain
- Atrial Natriuretic Factor
- imidapril
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Topics |
- Adult
- Aged
- Angiotensin-Converting Enzyme Inhibitors
(pharmacology, therapeutic use)
- Atrial Natriuretic Factor
(blood)
- Double-Blind Method
- Exercise Test
- Female
- Heart Failure
(blood, drug therapy)
- Humans
- Imidazoles
(pharmacology, therapeutic use)
- Imidazolidines
- Male
- Middle Aged
- Natriuretic Peptide, Brain
(blood)
- Renin-Angiotensin System
(drug effects)
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