Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis.
OBJECTIVE
Because aldosterone-dependent sodium and water retention contribute to portal hypertension, the safety and effect of an antialdosteronic drug (Kcanrenoate) have been evaluated on the occurrence of de novo appearance of ascites and the development of esophageal varices or the progression of small varices.


METHODS
Inclusion criteria were as follows: Child-Pugh A viral pre-ascitic cirrhosis, with either F1 esophageal varices or no varices, but endoscopic and/or ultrasound evidence of portal hypertension. Thirteen Italian Liver Units prospectively enrolled 120 patients randomized to receive double-blind either Kcanrenoate (100 mg/day; 66 patients) or placebo (54 patients). Endoscopy and sonography were performed at entry and at 52 weeks unless the patient developed ascites earlier, whereas laboratory examinations were performed at entry and every 3 months thereafter. An intention-to-treat analysis was performed, with each end point assessed by the Fisher exact test; the cumulative risk for the appearance of any end point was analyzed by the adjusted log-rank test (Tarone-Ware), with censoring for drop-outs.


RESULTS
The progression of variceal status or appearance of ascites, analyzed independently, was not significantly more frequent on placebo (24.1% and 9.2%, respectively) than on Kcanrenoate (12.1% and 1.5%, respectively), whereas the cumulative occurrence of end points was decreased on Kcanrenoate (17.6% vs 38.3% with placebo; P < .05, Tarone-Ware test). The incidence of adverse events was negligible and did not differ between groups.


CONCLUSIONS
This preliminary study shows that 100 mg/day of Kcanrenoate is well tolerated and does not reduce the individual incidence of ascites and/or the appearance or progression of esophageal varices in preascitc cirrhosis, but may decrease their 1-year cumulative occurrence.
Bolondi
Luigi
L
Division of Internal Medicine, Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy. bolondi@med.unibo.it
Piscaglia
Fabio
F
Gatta
Angelo
A
Salerno
Francesco
F
Bernardi
Mauro
M
Ascione
Antonio
A
Ferraù
Oscar
O
Sacerdoti
David
D
Visentin
Stefania
S
Trevisani
Franco
F
Mazzanti
Roberto
R
Donati
Gabriele
G
Arena
Umberto
U
Gentilini
Paolo
P
D000368:Aged; D001201:Ascites / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002191:Canrenoic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004932:Esophageal and Gastric Varices / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D015994:Incidence; D007677:Kidney Function Tests; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*
D000451:Mineralocorticoid Receptor Antagonists; D002191:Canrenoic Acid