Terapia diuretica combinata "Ab Initio" versus terapia diuretica sequenziale nel trattamento dell'ascite moderata in pazienti con cirrosi epatica senza insufficienza renale

Sequential versus "ab initio" combined diuretic treatment of moderate ascites in cirrhotic patients: preliminary results of a randomized controlled multicenter clinical study. Background: the most rational treatment of cirrhotic patients with moderate ascites is a stepwise sequential therapy with increasing oral doses of an aldosterone antagonist. If no response occurs at the maximum dosage of the aldosterone antagonist (400mg/day), furosemide is added at increasing oral doses in a stewise way up to 160 mg/day (sequential diuretic treatment). Nevetheless, the onset of response following a sequential diuretic trreatment of ascites may requires to much time. Aim of the study: as a consequence, the aim of the study was to compare sequential diuretic therapy with a schedule combining "ab initio" aldosterone antagonist and furosemide in the treatment of moderate ascites in nonazotemic cirrhotic patients. Material and method: sixty-eight nonazotemic cirrhotic patients with moderate ascites wererandomly assigned to be treated by sequential diuretic treatment (Group A, n°=37) or by "ab initio" combined diuretic treatment (Group B, n°=31). In patients of Group A, potassium kanrenoate was used at the initial dosage of 200 mg/day (1st step) and if no response was obtained, it was peaked to 400 mg/day (2nd step). In nonresponders to 400 mg/day of potassium kanrenoate, furosemide was added at the initial dosage of 50 mg b.i.d. (3rd step) eventually inceasing to 100 mg/day b.i.d. (4th step) and then up to 150 mg/day b.i.d. (common step). Patients of Group B received 200 mg/day of potassium kanrenoate and 50 mg b.i.d. of furosemide as 1st step. If no response was observed the dosages of potassium kanrenoate and furosemide were increased to 400 mg/day and 100 mg b.i.d. (2nd step) and then up to 400 mg/day and 150 mg b.i.d., respectively (3rd step).No response was defined as a three-day weight loss lower than 600 gr. Outcome: the response rate was similar in both groups (88 % in Group A vs 96 % in Group B, p= N.S.). The patients's rate that need to change the effective diuretic step for diureticinduced complications was significantly lower in Group B (20%) than in Group A (38%) (p <0,05). The mean time to mobilize ascites was shorter in patients of Group B than in patients of Group A (15.5 ±,9 vs 20.7 ±1.1 days, respectively, p = 0.001). Even excluding the time which was necessary to reach the effective diuretic regimen (5.0 ± 0.3 giorni nel gruppo B vs 6.0 ± 0.4 giorni nel gruppo A, p < 0.05) the mean time for the mobilization of ascites was greater in Group A than in Group B 10.6 ± 0.7 giorni nel Gruppo B vs 14,5 ± 1,0 giorni nel Gruppo A, p < 0.003). The multivariate analysis identified PRA value as predictive factor to develop adverse effects, indipendently from the type of diuretic treatment particularly when this value is > 10.2 ug/ml. Conclusions. "ab initio" combined diuretic treatment by means of potassium kanrenoate and furosemide makes it possible to shorten the time to mobilize moderate ascites in nonazotemic cirrhotic patients if comared to a sequential diuretic treatment. Thus, it appears the more suitable and cost-effective diuretic treatment schedule in these patients. Moreover, the probability to develop diuretic-induced adverse effects is correlated with basal value of plasma renin activity (PRA).