A randomized cross-over study of enalapril in congestive heart failure: Haemodynamic and hormonal effects during rest and exercise

Summary We performed a randomized double-blind placebo controlled cross-over study of enalapril in 16 patients with chronic congestive heart failure, to assess haemodynamic and hormonal effects at rest and on exercise. Acute effects were measured 4 h after enalapril 10 mg, and chronic effects after 6 weeks treatment with enalapril 10–20 mg per day.Exercise tolerance, assessed by the duration of a maximal bicycle ergometer test, was not altered by enalapril. Mean blood pressure was reduced after enalapril, at rest and on exercise, acutely by 7% and 8% respectively, and chronically by 14% and 16%. Systemic vascular resistance was reduced by 16% at rest both acutely (NS) and chronically (p<0.05). The resting pulmonary capillary wedge pressure was reduced by 28% with chronic treatment. In the acute study, total body oxygen consumption on exercise was 26% higher after enalapril. Chronically, resting oxygen consumption was reduced by 13% after enalapril, with mixed venous oxygen saturation increasing by 16%.In the acute study enalapril increased plasma renin activity at rest and on exercise by 181% and by 189%, and reduced aldosterone by 49% (NS) and 39% (p<0.05), and these effects were sustained after 6 weeks. Enalapril increased antidiuretic hormone concentrations at rest acutely by 73% (NS) and chronically by 34% (p<0.05) but not on exercise; the increase in the acute study correlated with plasma enalaprilat levels (r=0.66, p<0.05). Enalapril did not alter plasma catecholamine concentrations.Patients preferred enalapril to placebo, and radiographic heart size was reduced during chronic treatment. There were no serious adverse effects.We conclude that enalapril is an effective angiotensin converting enzyme inhibitor of clinical value in chronic heart failure, but study design and methods of assessment of benefit can have a major influence on the results of pharmacological studies in such patients.