Carvedilol therapy significantly decreased the risk for decompensated cirrhosis, ascites, and death in patients with compensated cirrhosis who developed clinically significant portal hypertension (CSPH), according to study findings published in the Journal of Hepatology.
Carvedilol is a vasodilator that can reduce hepatic vascular resistance and, therefore, decrease onset of portal hypertension in patients with compensated cirrhosis.
The efficacy of carvedilol in prevention of decompensated cirrhosis and mortality in the current study’s patient population remained unexamined until researchers conducted a systematic review and meta-analysis of the literature to compare outcomes of carvedilol treatment to no treatment, placebo, or endoscopic variceal ligation (EVL) in patients with compensated cirrhosis with CSPH.
Researchers evaluated 125 studies found through a thorough search of PubMed, MEDLINE, Embase, the Cochrane Collaboration Registry of Controlled Trials, and the Cochrane Database of Systematic Reviews up until February 2020. Of 125 randomized control trials identified, researchers determined only 4 were eligible for the analysis.
The 4 trials combined included a total of 352 patients with compensated cirrhosis — 181 of which received carvedilol and 171 control individuals who received either EVL (n=79) or placebo (n=92). In 2 trials, patients received up to 12.5 mg of carvedilol per day, while patients in the other 2 trials received up to 25 mg of carvedilol per day. The average length of follow-ups lasted from 13 to 36 months for the 4 trials.
After performing a careful meta-analysis, the researchers discovered that patients receiving carvedilol demonstrated significantly decreased risk of developing decompensated cirrhosis (subdistribution hazard ratio [SHR], 0.506; 95% CI, 0.289-0.887; P =.017), primarily due to reduced incidence of ascites (SHR, 0.491; 95% CI, 0.247-0.974; P =.042). Patients receiving carvedilol also demonstrated reduced mortality compared with control individuals (SHR, 0.417; 95% CI, 0.194-0.896; P =.025).
“Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH,” the study authors wrote. “This suggests that screening patients with compensated cirrhosis for CSPH to start therapy with carvedilol can improve outcomes.”
Study limitations included potential bias secondary to lack of double-blinding in included randomized control trials, inconsistencies in trial endpoint definitions, and lack of generalizability to patients with decompensated cirrhosis.
Villanueva C, Torres F, Sarin SK, et al. Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis. J Hepatol. Published online May 31, 2022. doi:10.1016/j.jhep.2022.05.021