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European Heart Journal 1992 13(11):1521-1527;
Copyright © 1992 by the European Society of Cardiology.
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© 1992 The European Society of Cardiology

Practical issues when initiating captopril therapy in chronic heart failure

What is the appropriate dose and how long should patients be observed?

J. S. MCLAY*,, J. MCMURRAY{dagger}, A. BRIDGES{ddagger} and A. D. STRUTHERS

*Department of Medicine and Therapeutics Polwarth Building, Foresterhill, Aberdeen AB9 2ZD
{dagger}Department of Cardiology, The Western Infirmary Glasgow Gll 6NT
{ddagger}Department of Pharmacology and Clinical Pharmacology, Ninewells Hospital and Medical School Dundee DD1 9SY, Scotland, U.K.

Received 29 August 1991; revised 4 March 1992; .

Correspondence: James S Mclay, Department of Medicine and Therapeutics, Polwarth Buildings, Foresterhill, Aberdeen AB9 2ZD, Scotland, U.K.

Abstract

To assess the feasibility of introducing captopril in patients with chronic heart failure on an outpatient rather than an inpatient basis a double-blind placebo-controlled study was carried out to compare either 6·25 mg or 25·0 mg of captopril as a starting dose; followed by either incremental doses of 6·25, 12·5, and 25·0 mg (low dose group), or 25·0 mg 8 hourly (high dose group) respectively. Forty-one patients in a general medical ward within a large teaching hospital with moderate to severe, stable, diuretic-controlled chronic heart failure, who were not hyponatraemic, hypokalaemic or on a dose of diuretic greater than 120 mg of frusemide took part.

No patient experienced symptomatic hypotension. Both doses of captopril produced a significant drop in blood pressure (BP), the magnitude of which was similar in both groups. The first dose-induced fall correlated significantly with subsequent dose-related reductions in BP. Therefore if a patient did not have a hypotensive response to the first dose of captopril he/she would be unlikely to have one with subsequent doses. In the group as a whole, the magnitude of the fall in BP after the first dose correlated significantly with starting plasma levels of angiotensin II, atrial natriuretic peptide (ANP), aldosterone, andrenin. However, on an individual basis, the two patients with the greatest fall in blood pressure did not have the most activated renin-angiotensin-aldosterone (RAA) system. This serves to emphasise the unpredictability of this response and the need to initiate therapy under clinical observation.

The size of the starting dose, therefore, does not significantly affect the magnitude of the BP fall, and there is a correlation between BP fall to the first and fourth doses. Thus, if there is no hypotensive response to the first dose, it should be safe to discharge patients from hospital observation. Therefore captopril can be initiated on an outpatient rather than as an inpatient basis, provided that patients are observed for at least 1·5 h following their first dose.

Key Words: Captopril • heart failure • hypotension • dose • blood pressure


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