PROGRESSION OF MILD UNTREATED HEART-FAILURE DURING 6 MONTHS FOLLOW-UPAND CLINICAL AND NEUROHUMORAL EFFECTS OF IBOPAMINE AND DIGOXIN AS MONOTHERAPY

There is increasing evidence that clinical deterioration in manifest c hronic heart failure is related to both hemodynamic and neurohumoral f actors. Only few data are available, however, on the progression of di sease in its early stages, when treatment has not yet been initiated. The aim of this study was therefore to examine the changes in clinical and neurohumoral variables that occur over 6 months in patients with clinically stable and untreated heart failure, and to evaluate the inf luence of drugs that may affect these variables. Accordingly, we studi ed 64 patients with heart failure who were in New York Heart Associati on functional class II (88%) and III (12%). They were randomized to do uble-blind treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n = 22), digoxin (0.25 mg once daily; n = 22) or placeb o (n = 20). Their age (mean +/- SD) was 60 +/- 8 years, and left ventr icular ejection fraction (mean +/- SD) was 0.33 +/- 0.08. Of the 64 pa tients, 56 (88%) completed the 6-month study period (p = NS between gr oups). Exercise time decreased in patients treated with placebo after 6 months (median -62 seconds; p <0.05 vs baseline), but it increased w ith ibopamine (+48 seconds), and digoxin (+17 seconds; both p <0.05 vs placebo). Plasma norepinephrine increased in the placebo group after 6 months (median +31 pg/ml, p <0.05 vs baseline), but decreased in pat ients receiving active drug treatment (ibopamine: -24 pg/ml, digoxin: -98 pg/ml, both p <0.05 vs placebol. Plasma renin and aldosterone leve ls were unchanged after 6 months in the placebo group, but digoxin the rapy slightly reduced plasma renin concentration (-5 mu U/ml; p <0.05 vs placebo). In conclusion, even in stable, untreated heart failure, a small but significant progression of disease occurs during 6 months, as reflected by both clinical and neurohumoral changes. Both ibopamine and digoxin monotherapy may favorably affect these changes, and may t hus be of value in this patient group.