Carvedilol for prevention of variceal bleeding: a systematic review and meta analysis

Abstract

Background Beta-blockers are used for prophylaxis of variceal bleeding. Our aim was to assess the efficacy and safety of carvedilol for primary or secondary prevention of variceal bleeding in patients with cirrhosis. Methods We searched Medline, Embase, CENTRAL and gray literature sources for randomized controlled trials (RCTs) comparing carvedilol with placebo or any active intervention. We synthesized data using random effects models. We summarized the strength of evidence using GRADE criteria. Results We included 13 trials with 1598 patients. Carvedilol was as efficacious as endoscopic variceal ligation (EVL) (4 RCTs, risk ratio [RR] 0.74, 95% confidence interval [CI] 0.37-1.49) or propranolol (3 RCTs, RR 0.76, 95%CI 0.27-2.14) for primary prevention of variceal bleeding. Likewise, carvedilol was as efficacious as EVL (3 RCTs, RR 1.10, 95%CI 0.75-1.61), non-selective beta-blockers (NSBBs) plus isosorbide-5-mononitrate (2 RCTs, RR 1.02, 95%CI 0.70-1.51) or propranolol (2 RCTs, RR 0.39, 95%CI 0.15-1.03) for secondary prevention of variceal bleeding. Carvedilol was associated with lower all-cause mortality compared to EVL (3 RCTs, RR 0.51, 95%CI 0.33-0.79). There was no difference in any other efficacy outcome. Finally, there were no significant differences in the safety profiles compared with EVL and NSBBs. Our confidence in the effect estimates for all outcomes was very low. Conclusion Carvedilol is as efficacious and safe as standard-of-care interventions for the primary and secondary prevention of variceal bleeding.

Non‐selective beta‐blockers in patients with ascites: The complex interplay among the liver, kidney and heart

“…This revolutionary observation spearheaded a titanic amount of research work in the coming years, resulting in the accumulation of robust evidence from numerous randomized clinical trials (RCTs) and several meta‐analyses supporting the safety and usefulness of propranolol in treating cirrhosis 2 . As a result of these studies, we now know that NSBBs prevent the first and recurrent episodes of portal hypertension‐related bleeding 3‐19 . More importantly, because of their portal pressure‐reducing effect, NSBBs are the only non‐aetiological drugs shown to prevent cirrhosis decompensation and improve survival, both in compensated and decompensated patients 20‐22 …”

Evaluation of liver transplant candidates with non-alcoholic steatohepatitis

“…Diuretics and nonselective beta-blockers are ideal first-line antihypertensive therapies in cirrhotic patients with ascites or varices. NASH patients with co-morbid heart failure and CAD may preferentially be treated with carvedilol, which is also effective in variceal hemorrhage prophylaxis (88). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are potential second-line antihypertensive agents.…”

Managing liver cirrhotic complications: Overview of esophageal and gastric varices

“…35 This study also showed that there was no difference in the incidence of all-cause mortality between carvedilol and EVL or propranolol. 42 Hence, carvedilol is an effective and safe alternative for primary prophylaxis of EV bleeding. Evidence also recommends EVL as an effective alternative.…”