|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 1998; 32:1811-1818 © 1998 by the American College of Cardiology Foundation |
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
Manuscript received May 5, 1998; revised manuscript received July 13, 1998, accepted August 6, 1998.
Address for correspondence: Dr. D.J. van Veldhuisen, Department of Cardiology/Thoraxcenter, University Hospital Groningen, PO Box 30 001, 9700 RB Groningen, The Netherlands
d.j.van.veldhuisen{at}thorax.azg.nl
Objectives. To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril.
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.
| ||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  L. H. Ficociello, B. A. Perkins, K. H. Silva, D. M. Finkelstein, H. Ignatowska-Switalska, Z. Gaciong, L. A. Cupples, A. Aschengrau, J. H. Warram, and A. S. Krolewski Determinants of Progression from Microalbuminuria to Proteinuria in Patients Who Have Type 1 Diabetes and Are Treated with Angiotensin-Converting Enzyme Inhibitors Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 461 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dolezal Review: Imidapril in Heart Failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2006; 7(3): 146 - 154. [Abstract] [PDF]
|
|
|
|
 |
|
 D. M. McNamara, R. Holubkov, L. Postava, K. Janosko, G. A. MacGowan, M. Mathier, S. Murali, A. M. Feldman, and B. London Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2019 - 2026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bruins, M. R. Fokkema, J. W.P. Romer, M. J.L. DeJongste, F. P.L. van der Dijs, J. M.W. van den Ouweland, and F. A.J. Muskiet High Intraindividual Variation of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in Patients with Stable Chronic Heart Failure Clin. Chem., November 1, 2004; 50(11): 2052 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. de Denus, C. Pharand, and D. R. Williamson Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone Chest, February 1, 2004; 125(2): 652 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A Sica and T. W. Gehr Review: The pharmacokinetics and pharmacodynamics of angiotensin-receptor blockers in end-stage renal disease Journal of Renin-Angiotensin-Aldosterone System, December 1, 2002; 3(4): 247 - 254. [Abstract] [PDF]
|
|
|
|
 |
|
 M.R. Abraham, L. J. Olson, M. J. Joyner, S. T. Turner, K. C. Beck, and B. D. Johnson Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure Circulation, October 1, 2002; 106(14): 1794 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.A. Cooke, S.G. Williams, P. Marshall, J.K. Al-Timman, J. Shelbourne, D.J. Wright, and L.-B. Tan A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients Eur. Heart J., September 1, 2002; 23(17): 1360 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. H. Wilson Tang, R. H. Vagelos, Y.-G. Yee, C. R. Benedict, K. Willson, C. L. Liss, P. LaBelle, and M. B. Fowler Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure J. Am. Coll. Cardiol., January 2, 2002; 39(1): 70 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I I Tulevski, M Groenink, E E van der Wall, D J van Veldhuisen, F Boomsma, J Stoker, A Hirsch, J S Lemkes, and B J M Mulder Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction Heart, July 1, 2001; 86(1): 27 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. M. van den Heuvel, P. H. J. M. Dunselman, T. Kingma, P. Verhorst, F. Boomsma, W. H. van Gilst, and D. J. van Veldhuisen Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade J. Am. Coll. Cardiol., February 1, 2001; 37(2): 470 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R J MacFadyen, C G Fraser, and A D Struthers Intermittent non-adherence with ACE inhibitor treatment and its implications for clinical trials results Heart, February 1, 2001; 85(2): 213 - 214. [Full Text]
|
|
|
|
|
|
H. M. Krumholz, D. W. Baker, C. M. Ashton, S. B. Dunbar, G. C. Friesinger, E. P. Havranek, M. A. Hlatky, M. Konstam, D. L. Ordin, I. L. Pina, et al. Evaluating Quality of Care for Patients With Heart Failure Circulation, March 28, 2000; 101 (12): e122 - e140. [Full Text] [PDF]
|
|
|
|
|
|
B.-q. Zhu, Y.-p. Sun, R. E. Sievers, A. E. M. Browne, S. Pulukurthy, K. Sudhir, R. J. Lee, T. M. Chou, K. Chatterjee, and W. W. Parmley Comparative effects of pretreatment with captopril and losartan on cardiovascular protection in a rat model of ischemia-reperfusion J. Am. Coll. Cardiol., March 1, 2000; 35(3): 787 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Young Angiotensin-converting enzyme inhibitors and cytokines in heart failure: dose and effect? J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2068 - 2071. [Full Text] [PDF]
|
|
|
|
|
|
A. D. Struthers, R. MacFadyen, C. Fraser, J. Robson, J. J. Morton, C. Junot, and E. Ezan Nonadherence with angiotensin-converting enzyme inhibitor therapy: A comparison of different ways of measuring it in patients with chronic heart failure J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2072 - 2077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A D Struthers, G Anderson, R J MacFadyen, C Fraser, and T M MacDonald Non-adherence with ACE inhibitor treatment is common in heart failure and can be detected by routine serum ACE activity assays Heart, November 1, 1999; 82(5): 584 - 588. [Abstract] [Full Text]
|
|
|
|
 |
|
 High-Dose ACE Inhibition Better for CHF Journal Watch (General), December 22, 1998; 1998(1222): 2 - 2. [Full Text]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
