Delayed effects of one-year treatment with low-dose as compared with high-dose enalapril on morbidity and mortality of patients with severe heart failure

Journal of Clinical and Basic Cardiology 1998; 1 (1): 19-24

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Keywords: Enalapril,  Ergometrie,  Herzinsuffizienz,  Morbidität,  Mortalität,  Enalapril,  exercise tolerance,  heart failure,  morbidity,  mortality

Uptitrating severe heart failure patients from a conventional low dose of enalapril to a high dose yields more favourable clinical results in severe heart failure patients treated with high dose than with low dose. To investigate subsequent effects on morbidity and mortality of high dose enalapril, an open two-year extension study was performed with all patients receiving the high dose. Of 83 New York Heart Association class III?IV patients (83 % male, aged 27?74 years; mean 55), 43 patients had completed the one year basic study. 41 patients (18 patients in the low-dose extension group and 23 patients in the high-dose extension group) entered extension and received 40 mg enalapril per day. Clinical status, exercise capacity and kidney function were assessed at months 15, 18, 24, 30 and 36 and survival rates were evaluated at month 36 after randomisation. At month 15 the change in New York Heart Association score was similar in both treatment groups, but at month 18 New York Heart Association score decreased more in the high-dose extension group than in the low-dose extension group (-0.8 vs -0.5, p < 0.05) with no further difference between the groups up to 36 months. At month 24 exercise capacity increased more in the high-dose extension group than in the low-dose extension group (p < 0.05), whereas heart rate and peripheral blood pressure at maximal exercise were similar in both groups. Except for a larger drop in systolic (p < 0.05) and diastolic (p < 0.05) resting blood pressure in the high-dose extension group, both groups had a similar safety profile, including kidney function. Three patients in the low-dose extension group and 13 patients in the high-dose extension group completed the open extension study. At the end of the study at month 36 there were 12 heart transplants (7 in the low dose extension group versus 5 in the high-dose extension group) and 22 deaths (15 in the low dose extension group versus 7 in the high-dose extension group) resulting in a significant improvement in survival (p < 0.05). The present data suggest a marked clinical benefit from maximising ACE-inhibitor doses in patients with severe heart failure. While symptomatic improvement may appear as the first response secondary to uptitrating enalapril to a more vigorous dose, enhanced exercise tolerance seems to warrant prolonged high enalapril treatment and may finally translate into a survival benefit. J Clin Bas Cardiol 1998; 1: 19-24.