Epidemiology

REFILE: Combined diuretic therapy preferred for ascites

Last Updated: 2009-12-23 11:55:15 -0400 (Reuters Health)

[Corrects byline of 20091222epid004, posted Dec. 22, 2009.]

By Dave Levitan

NEW YORK (Reuters Health) - In patients with ascites who don't have renal failure, combining an aldosterone antagonist and a loop diuretic is preferable to sequential administration of these agents, a randomized Italian trial has shown.

A previous trial determined that sequential therapy is preferable, but it included a large proportion of previously untreated patients. According to the current report, published in the January issue of Gut, this is relatively uncommon in clinical practice.

Led by Dr. Paolo Angeli of the University of Padova, the researchers randomized 100 cirrhotic patients with moderate ascites and normal kidney function to receive either sequential or combined diuretic treatment. One patient in the sequential group was excluded from the final analysis because of a liver transplant, along with one in the combined group who did not comply with study protocol.

Patients in the sequential group received an initial dose of the aldosterone antagonist potassium canrenoate 200 mg/day, followed by an increase to 400 mg/day. Non-responders then received 50 mg/day of the loop diuretic furosemide in addition to the potassium canrenoate, increased through 100 mg/day to 150 mg/day until a response was achieved.

In the combined group, patients were treated with an initial potassium canrenoate dose of 200 mg/day along with furosemide at 50 mg/day. The investigators then increased the doses to 400 mg/day and 150 mg/day, respectively.

An "effective diuretic step" -- defined as a body weight loss greater than 700 g every three days - was achieved by 44 of 50 patients (88%) in the sequential group and 48 of 50 (96%) in the combined group (p = NS). The average time to achieve the effective step was shorter in the combined group (5.0 days) than in the sequential group (6.6 days; p < 0.0025).

In addition, the effective diuretic step was step 1 in a larger percentage of patients in the combined therapy group (55%) than in the sequential therapy group (30%).

The combined treatment group had a lower rate of adverse effects compared to the sequential group (20% vs. 38%; p < 0.05). When effects and failures to achieve an effective diuretic step were combined, the total number of treatment failures was 44% in the sequential group, significantly higher than the 24% in the combined group (p < 0.05).

The study's main limitation is its exclusion of patients with renal dysfunction, Dr. Angeli told Reuters Health in an e-mail. He added that the combination treatment "is cheaper, because it reduces the time which is needed to obtain both an effective diuretic step and the resolution of ascites.... I think (this) will be a definitive answer to this clinical problem."

Gut 2010;59:98-104.