Copyright © 1996 by the European Society of Cardiology.
© 1996 The European Society of Cardiology
Effects of two different enalapril dosages on clinical, haemodynamic and neurohumoral response of patients with severe congestive heart failure
Department of Cardiology Vienna, Austria
*Occupational Medicine, University of Vienna Vienna, Austria
Danube Hospital Vienna, Austria
revised 10 January 1996; accepted 10 January 1996.
Correspondence: Richard Pacher, Department of Cardiology, University of Vienna, Wahringer Gurtel 18–20, A-1090 Vienna, Austria
Abstract
Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patient is uncertain. A randomized, 48-week, double-blind study was performed to investigate the safety and efficacy of 0‘high’ in comparison to continued ‘low’ angiotensin converting enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 ±11 years; 69 men, 14 women) in New York Heart Association functional class III/TV on digoxin, furosemide and ‘low’ angiotensin converting enzyme inhibitors (captopril 
50mg.day–1 or enalapril 10 mg. day–1) were included. After a 14 day run-in on lOmg.day–1 enalapril, digitalis and furosemide, right heart catheteriz-ation at rest and exercise was performed. All patients presented with atrial pressure >10mmHg and/or pulmonary artery pressure >35mmHg, and/or cardiac index <2·51. min–1. m–2 at rest. Patients then received enalapril 5 mg twice daily (n=42), or 20 mg twice daily (n=41) in random order. Thus, patients randomized to low doses of enalapril actually had no change in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high dose. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P=004). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P=0·01). Changes in plasma creatinine levels did not differ between high and low dose treatment and no patients had to be withdrawn because of deterioration in kidney function. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in noradrenaline on high versus low enalapril dose. Thus, high-dose enalapril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effects on haemodynamics and on maximal exercise capacity.
Key Words: Angiotensin converting enzyme inhibition • low and high dose enalapril • severe heart failure • symptomatology • noradrenaline, big endothelin
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