Clinical and neurohumoral response of patients with severe congestive heart failure treated with two different captopril dosages.

Although angiotensin converting enzyme inhibitor therapy is an established approach in the treatment of chronic heart failure, the required dosage remains unclear. This open 6 month study investigated the influence of different captopril dosages on the clinical course and neurohumoral activity of patients with severe heart failure (left ventricular ejection fraction < or = 20%). Eighty-five patients in New York Heart Association class II-IV despite treatment with digitalis, diuretics, and captopril (mean dose +/- SEM 28 +/- 2 mg.day-1 at baseline) for > or = 3 months received either 'low dose' captopril (< 75 mg.day-1, mean 32 +/- 2 mg.day-1; n = 46) or 'high dose' captopril (> or = 75 mg.day-1, mean 99 +/- 4 mg.day-1; n = 39) during the follow-up period. Both groups were comparable in clinical, haemodynamic and neurohumoral parameters at baseline. Functional state improved significantly only in the high dose group (P < 0.0001). Of 31 low dose and 20 high dose patients considered as heart transplantation candidates at baseline, 21 low dose and only six high dose patients remained on the waiting list (P < 0.0001). In patients in the low dose group, eight deaths were observed (P < 0.001). Seven patients remained on low dose captopril due to adverse effects. The initially elevated plasma levels of aldosterone and atrial natriuretic peptide decreased significantly only in high dose patients (P < 0.01). Renin increased significantly in both groups. These observations underline the necessity of suppressing neurohumoral overactivation with adequate doses of captopril reflected by sequential humoral plasma determination.