Published online Dec 7, 2017. doi: 10.3748/wjg.v23.i45.8062
Peer-review started: September 14, 2017
First decision: October 10, 2017
Revised: October 25, 2017
Accepted: November 8, 2017
Article in press: November 8, 2017
Published online: December 7, 2017
Recently, several studies have evaluated the effects of aquaretic drugs such as tolvaptan for treating ascites resistant to conventional therapies.
Whether a combination therapy with natriuretic and aquaretic drugs is more effective than conventional therapy with natriuretic for liver cirrhosis patients with ascites remains unclear.
We assessed the effects of a combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients.
A two-center, randomized, open-label, prospective study was conducted. Japanese patients who met the criteria were randomized to trial groups and they received an aquaretic drug (7.5 mg of tolvaptan) or a natriuretic drug (40 mg of furosemide) for 7 d in addition to the natriuretic drug which was used prior to enrolment in this study. The primary endpoint was the change in body weight from the baseline. Vital signs, fluid intake, and laboratory and urinary data were assessed to determine the pharmacological effects of tolvaptan and furosemide.
A total of 56 patients were randomized to receive either tolvaptan (n = 28) or furosemide (n = 28). In the tolvaptan and furosemide groups, the average decrease in body weight from the baseline was 3.21 ± 3.17 kg (P < 0.0001) and 1.75 ± 2.36 kg (P = 0.0006), respectively, when measured on the final dosing day. Following 1 wk of treatment, a significantly greater reduction in body weight was observed in the tolvaptan group compared to that in the furosemide group (P = 0.0412).
Compared to a conventional therapy with only natriuretic drugs, a combination therapy with natriuretic and aquaretic drugs is more effective for patients with cirrhotic ascites. Following 1 wk of treatment, a significantly greater reduction in body weight was observed in the combination therapy compared to that in the conventional therapy. Combination therapy that involves the blocking of sodium and water reabsorption may be more effective in treating liver cirrhosis with ascites than conventional therapy, which only blocks sodium reabsorption. Combination therapy including tolvaptan and conventional diuretics reduced the occurrence of diuretic-related severe side effects. A two-center, randomized, open-label, prospective study was conducted. The criteria were randomized to a trial group and the combination diuretic group (natriuretic and aquaretic drugs) or the conventional diuretic group (a natriuretic drug only). A combination diuretic therapy including an aquaretic drug resulted in a greater decrease in body weight compared to conventional diuretic with only a natriuretic drug for cirrhotic ascites patients. Moreover, compared to conventional diuretic therapy, combination diuretic therapy reduced the occurrence of diuretic-related severe side effects. Compared to a conventional diuretic therapy with only a natriuretic drug, a combination diuretic therapy with natriuretic and aquaretic drugs proved to be more effective for patients with cirrhotic ascites. Combination therapy may establish a strategy to treat ascites refractory to the standard diuretic therapy.
The study compared to a conventional diuretic therapy with only a natriuretic drug, a combination diuretic therapy with natriuretic and aquaretic drugs is more effective for patients with cirrhotic ascites. It is not clear whether or not the combination therapy improved the long-term prognosis of these patients. Therefore, future long-term observational studies are warranted. The future research should assess the influence of renal function after the administration of tolvaptan and furosemide in liver cirrhosis patients with ascites for at least 24 wk.