Long-term carvedilol therapy reduces decompensation risk among cirrhosis patients

Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. They assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH).

By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. They performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach.

Results:

Among 125 full-text studies evaluated, 4 RCTs were eligible.

• The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo).
• Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls, mainly due to a reduced risk of ascites
• The risk of death was also lower with carvedilol

Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes.

Reference:

Càndid Villanueva, et al. Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis. May 31, 2022. DOI: https://doi.org/10.1016/j.jhep.2022.05.021

Keywords:

Càndid Villanueva, Ferran Torres, Shiv Kumar Sarin, Edilmar Alvarado, Jaume Bosch, Carvedilol, reduces, risk, decompensation, mortality, patients, compensated, cirrhosis, competing-risk meta-analysis, Journal of Hepatology