Efficacy of combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients: A randomized study

Abstract

AIMTo assess the effects of a combination therapy with natriuretic and aquaretic drugs in cirrhotic ascites patients.METHODSA two-center, randomized, open-label, prospective study was conducted. Japanese patients who met the criteria were randomized to trial group and the combination diuretic group (received 7.5 mg of tolvaptan) or the conventional diuretic group (received 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 after administration of aquaretic and natriuretic drugs.RESULTSA total of 56 patients were randomized to receive either tolvaptan (n = 28) or furosemide (n = 28). In the combination and conventional diuretic 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 combination diuretic group compared to that in the conventional diuretic group (P = 0.0412).CONCLUSIONCompared 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.

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study)

“…This rationale is justified as the higher doses of conventional diuretics can cause ADRs such as renal impairment [7]. Instead, adding tolvaptan to a treatment regimen seems to be a better option than using conventional diuretics; tolvaptan does not seem to impair renal function in clinical practice [19][20][21], thereby reducing the ADRs in clinical practice.…”

Curative Effect and Safety of Tolvaptan Combined with Traditional Diuretics in Treatment of Patients with Cirrhotic Ascites and Relevant Research on its Dose: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

“…And, the occurrence rates of total adverse events, diarrhea and frequency of urination were evaluated under different dose. 5 studies report the total incidence of adverse events (including 620 patients) in the intervention process [16][17][18][19][20]. Mate analysis result shows that in the intervention process, the total incidence of adverse events was obviously higher than that of traditional diuretic group (OR=1.98, 95%CI [1.11, 3.52], P=0.02, Fig 5A).…”

“…In the aspect of minor indexes, the changes in the average weight, average waistline and average ascites amount are reported in 4 studies (499 patients) [17][18][19][20], 3 studies (440 patients) [17][18]20], and 2 studies (216 patients) [17,19], respectively. The changes of urine volume on the first day of intervention compared with the last day are reported in 4 studies (498 patients) [16][17][19][20][21]. After the intervention for 7 days, the reduction of average weight (WMD=-1.51Kg, 95%CI [-1.86, -1.16], P<0.001, Fig 2A), average abdominal girth (WMD=-2.05cm, 95%CI [-2.67, -1.43], P<0.001, Fig 2B), and the average ascites amount (WMD=-293.43mL, 95%CI [-502.53, -84.34], P=0.006, Fig 2C) of combined diuretic group was obviously better than that of traditional diuretic group.…”

Management of portal hypertension and ascites in polycystic liver disease

“…Additionally, a phase 2 trial has shown that tolvaptan significantly reduced the body weight and abdominal circumference compared to placebo in patients with liver cirrhosis‐associated ascites . Another randomized trial showed that a combination of conventional natriuretic drugs and tolvaptan was superior to conventional therapy alone in cirrhosis‐associated ascites …”

“…58 Another randomized trial showed that a combination of conventional natriuretic drugs and tolvaptan was superior to conventional therapy alone in cirrhosis-associated ascites. 59 Two recent case reports have suggested that tolvaptan may also reduce liver volume. 60,61 The potential effect was corroborated by an in vitro study that showed involvement of vasopressin in liver cyst growth.…”