Efficacy and Safety of Carvedilol in Cirrhosis Patients With New-Onset Uncomplicated Ascites Without High-Risk Esophageal Varices (CARVE-AS Trial).

INTRODUCTION

Carvedilol is effective in the prevention of bleeding in patients with cirrhosis and high-risk varices. Although it reduces drivers of clinical decompensation (portal pressure, systemic inflammation, and bacterial translocation), the data on its use for prevention of ascites-related complications are limited.

METHODS

In this open-label randomized control tria, patients having uncomplicated new-onset ascites with no or low-risk esophageal varices were randomized (n = 104) to receive carvedilol (group A, n = 52) or no carvedilol (group B, n = 52) in addition to standard treatment. The composite primary outcome was incidence of any ascites-related complications, namely, spontaneous bacterial peritonitis, hepatorenal syndrome acute kidney injury, refractory ascites, or severe hyponatremia at 1 year. The secondary outcomes included need for paracentesis, change in hepatic venous pressure gradient, Child-Turcotte-Pugh, and Model for End-Stage Liver Disease score and mortality at 1 year.

RESULTS

The baseline characteristics were comparable between the groups, with metabolic dysfunction-associated steatotic liver disease as the commonest etiology (overall 41.3%) followed by alcohol-associated liver disease (21.2%). Patients in group A compared with group B had lower incidence of complicated ascites (38.5% vs 67.3%; P = 0.03), mainly related to reduced incidence of acute kidney injury (AKI) (34.6% vs 63.4%, P = 0.003), refractory ascites, and spontaneous bacterial peritonitis along with a significant reduction in HVPG (14.89 ± 2.8 to 11.86 ± 1.9 mm Hg [ P < 0.05]) and lesser progression in variceal grade (21.8% vs 53.1%, P = 0.009). Patients in group A than B demonstrated better ascites resolution (61.5% vs 31.8%, P = 0.01) and fewer large volume paracentesis sessions (26.9% vs 57.6%; P = 0.01). At 1 year, patients in group B had higher Child-Turcotte-Pugh scores (9.31 ± 1.43 vs 8.17 ± 1.7, P = 0.001). Use of carvedilol was associated with lower 1 year mortality (9.1% vs 24.2%, P = 0.05). No patient had treatment-related severe adverse events.

DISCUSSION

Administration of carvedilol in patients with cirrhosis with new-onset uncomplicated ascites without high-risk varices is safe and prevents further ascites-related complications, with reduced need for large volume paracentesis and improved survival.