HEMODYNAMIC AND HORMONAL EFFECTS OF A PAR ENTERAL THERAPY WITH THE ACE-INHIBITOR QUINAPRILAT IN PATIENTS WITH ADVANCED HEART-FAILURE

The hemodynamic and neurohumoral effects of single and multiple doses of intravenous quinaprilat were assessed and compared with placebo in a double-blind design. The study group included 50 patients aged betwe en 33 and 76 years with NYHA Class III, and IV heart failure. The pati ents were randomized into three treatment groups to receive low (0.5 a nd 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) intrave nous doses of quinaprilat or placebo on day 1, and, based on the respo nses, q6h on two further days. The hemodynamic parameters were determi ned by right-heart catheterization. Quinaprilat is the active metaboli te of quinapril, an ACE inhibitor with high affinity for the angiotens ine converting enzyme, which is formulated for oral application. Compa red with placebo, single and multiple doses of quinaprilat increased c ardiac index by 25 % (p < 0.05) and simultaneously decreased both peri pheral vascular resistance by 25 % (p < 0.05) and left ventricular fil ling pressures by 33 % (p < 0.05). There was a dose-related decrease i n mean right atrial pressure by 47 % (p < 0.05) without significant he art rate changes (-3-5 bpm). The mean artery pressure showed a dose-re lated maximum decrease of 4-9 mm Hg 45-60 min after single-dose quinap rilat and of 7-10 mm Hg (p < 0.05) after repetitive dosing. Maximum ch anges were observed 15-90 min after drug application. The hemodynamic changes after multiple-dose quinaprilat were similar to those observed following single doses and generally persisted during the total obser vation period of 6 h. Compared with placebo, quinaprilat reduced ACE a ctivity and angiotensin II and aldosterone concentrations, and increas ed plasma renin activity. There were no significant changes with regar d to plasma catecholamines and the atrial natriuretic factor, although a slight decrease could be observed.The study results obtained in pat ients with advanced heart failure support both the safety and favorabl e hemodynamic and neurohumoral effects of intravenous quinaprilat over an observation period of 3 days.