Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety☆,☆☆
Introduction
Ascites is the most frequent complication of cirrhosis and it is associated with a worsening of the prognosis of these patients. The estimated probabilities of survival at 1 and 5 years after the development of ascites are of 50% and 20%, respectively [1], [2].
While therapeutic paracentesis is the first treatment of choice in tense ascites, treatment of moderate ascites should initially include both salt restriction and diuretics simultaneously, since a positive response to diet alone is slow, and rare (approximately 14% of cirrhotic patients with ascites) [3], [4], [5].
The most rational diuretic treatment of cirrhotics with moderate ascites is spironolactone alone or in combination with furosemide [6], [7], [8]. Two different diuretic schedules are usually used in these patients. The first one consists of the administration of increasing doses of spironolactone, adding furosemide only to those patients not responding to the highest recommended doses of the former (400 mg/day). The second one consists of starting with the simultaneous administration of furosemide and spironolactone increasing the doses of both diuretics if no therapeutic response is achieved. Although stepwise sequential therapy with increasing oral doses of an aldosterone antagonist may be effective in mobilizing ascites in 60–80% of nonazotemic cirrhotic patients with ascites who did not respond to bed rest and dietary sodium restriction [5], [9], to our knowledge in only one study, a relatively low number of cirrhotic patients with ascites and without overt oliguric renal failure has been randomized to be treated with furosemide, combination therapy with furosemide and spironolactone or sequential spironolactone (spironolactone followed by furosemide if necessary) [10]. Therefore, we performed a randomized study comparing spironolactone alone versus spironolactone associated with furosemide, in terms of efficacy and safety, in nonazotemic cirrhotic patients with moderate ascites.
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Patients
We studied 127 consecutive nonazotemic cirrhotic patients admitted to our hospitals for treatment of moderate ascites. The following criteria were required for inclusion in the study: grade 2 ascites, serum creatinine ≤1.5 mg/dl, urinary sodium excretion <50 mmol/day, serum sodium ≥125 mmol/l, and serum potassium <5.5 mmol/l, after 5 days on a 50 mmol/day sodium diet and without diuretics, as well as absence of gastrointestinal bleeding, hepatic encephalopathy, infection, advanced hepatocellular
Results
Twelve of 127 patients with moderate ascites observed during the study period were not included due to serum creatinine >1.5 mg/dl (3 patients), serum sodium <125 mEq/l (2), advanced hepatocellular carcinoma (2), grastrointestinal bleeding (2), urinary infection (1) and spontaneous bacterial peritonitis (2). Moreover, low sodium diet and bed rest induced ascites mobilization in 15 out of 115 patients (13%) during the previous 5 days before randomization.
Therefore, 100 nonazotemic cirrhotics
Discussion
Since the study by Pérez-Ayuso et al. [6], showing that spironolactone is more effective than furosemide in nonazotemic cirrhotic patients with ascites, it has been well established that increasing doses of spironolactone alone or associated with furosemide are the most suitable approaches to the treatment of these patients, while the single administration of furosemide is not recommended because this drug alone fails to increase the urinary sodium excretion in approximately 50% of cases [6].
Acknowledgements
Supported in part by a grant from the Instituto Carlos III (C03/02).
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Preliminary results of this study were presented at the 50th Annual Meeting of the American Association for the Study of Liver diseases held in Dallas (November, 1999) and the 35th Annual Meeting of the European Association for the Study of the Liver held in Rotterdam (April–May, 2000).
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The authors who have taken part in this study have not a relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research.