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High- versus low-dose ACE inhibition in chronic heart failure

A double-blind, placebo-controlled study of imidapril

Dirk J. van Veldhuisen, MD, PhD, FACC^a,1, Sabine Genth-Zotz, MD^*, Jan Brouwer, MD, PhD^a, Frans Boomsma, PhD, Tilo Netzer, PhD, Arie J. Man in ’t Veld, MD, PhD, Yigal M. Pinto, MD, PhD^||, K. I. Lie, MD, PhD and Harry J. G. M. Crijns, MD, PhD^a

^a Department of Cardiology/Thoraxcenter, University Hospital Groningen, Groningen, The Netherlands
^* the II. Medical Clinic, Johannes Gutenberg-University Clinic, Mainz, Germany
COEUR/Department of Internal Medicine I, University Hospital Dijkzigt, Rotterdam, The Netherlands
Clinical Research, Merck KGaA, Darmstadt, Germany
^|| the Institute of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands
the Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands

View larger version (19K): [in a new window]   Figure 1 (A) Change after 12 weeks of treatment in exercise duration (s) in the four groups. *p < 0.05 vs. placebo; #p < 0.05 vs. 2.5-mg imidapril. A significant dose-response relation was observed by the linear trend test (p = 0.019). (B) Change after 12 weeks of treatment in physical (or pulse) working capacity (PWC) in watts at a heart rate of 110 beats/min (PWC110). *p < 0.05 vs. placebo. There was also a significant dose-response effect (p < 0.05).

View larger version (29K): [in a new window]   Figure 2 (A) Change after 12 weeks of treatment in plasma norepinephrine concentrations (in pg/ml), at rest (open bars) and peak exercise (solid bars). There are no significant differences. (B) Change after 12 weeks of treatment in plasma renin (µU/ml), at rest (open bars) and peak exercise (solid bars). *p < 0.05 vs. placebo; **p < 0.001 vs. placebo; #p < 0.05 vs. 2.5-mg imidapril. The dose-response relation was significant both at rest and during exercise (p < 0.05 by linear trend). (C) Change after 12 weeks of treatment in plasma ACE (in % from baseline), at rest (open bars) and peak exercise (solid bars). All differences are highly significant vs. placebo (p < 0.001) but there is no dose-response relation. (D) Change after 12 weeks of treatment in plasma BNP (pg/ml), at rest (open bars) and peak exercise (solid bars). *p < 0.05 vs. placebo. The effect on BNP is dose-dependent, both at rest and during exercise (both p < 0.05).