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European Heart Journal 1994 15(Supplement D):113-122; doi:10.1093/eurheartj/15.suppl_D.113
Copyright © 1994 by the European Society of Cardiology.
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© 1994 The European Society of Cardiology

Dose-Related Effects of ACE Inhibition in Man: Quinapril in Patients with Moderate Congestive Heart Failure

J. Nussberger*,, E. Fleck{dagger}, H. Bahrmann{ddagger}, W. Delius§, H. P. Schultheiss||, H. R. Brunner* For the Study Group on Neurohormonal Regulation in Congestive Heart Failure: Lausanne, Switzerland; Berlin, Düsseldorf, Munich, German

* University Hospital Lausanne, Switzerland
{dagger} Deutsches Herzzentrum Berlin, Germany
{ddagger} Gödecke/Parke-Davis Co., Clinical Research Department Freburg, Germany
§ Städtisches Krankenhous Bogenhausen Munich, Germany
|| Medizinische Klinik, Heinrich Heine Universität Düsseldorf, Germany

Correspondence: Jürg Nussberger, MD, Hypertension Division, CHUV - Hôpital Nestlé, 1011 Lausanne, Switzerland

Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate In 55 patients with moderate heart failure (ejection fraction ≤ 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodymmics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased All these parameters including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang If occurred with quinapril 20 mg.day–1. Humoral changes appeared more assessible than haemodymmic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failure.

Key Words: Renin (PRA) • angiotensin I • angiotensin II • angiotensin converting enzyme (ACE) • atrial natriuretic factor (ANF) • norepinephrine • epinephrine • exercise


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