Comparison of the effectiveness of 11 mainstay treatments for secondary prophylaxis of variceal bleeding in patients with cirrhosis: A network meta‑analysis

Abstract

The purpose of the present study was to compare the effectiveness of the transjugular intrahepatic portosystemic shunt (TIPS), endoscopic options, medications and mainstay combination therapies for patients with cirrhosis who have had at least one episode of variceal haemorrhage. The PubMed, Embase, Cochrane Library and Web of Science databases, as well as the reference lists of relevant articles, were searched to identify eligible studies. P-scores, that were based solely on the point estimates and standard errors of the network estimates, were performed to rank all treatments, on a scale from 0 (worst) to 1 (best). The odds ratio (OR) was determined to assess effects on mortality, treatment failure and bleeding from gastroesophageal ulcers. A total of 43 randomized controlled trials comprising 3,787 adult patients were included. In total, 26 (61%) trials adopted concealed randomization, while most studies did not specify blinding. The drug combination of nadolol and isosorbide mononitrate (ISMN) ranked first for lowering risks of overall mortality (P-score=0.8162), mortality due to liver failure (P-score=0.7536) and bleeding from gastroesophageal ulcers (P-score=0.7536). This combination was determined to be superior to endoscopic sclerotherapy (ES) alone (OR=0.63, 95% CI: 0.42-0.94) and TIPS alone in reducing overall mortality (OR=0.62, 95% CI: 0.40-0.96). ES was more likely to increase treatment failure compared with TIPS, endoscopic variceal liga-tion (EVL), ES plus EVL, EVL plus nadolol/propranolol plus ISMN and nadolol/propranolol plus ISMN. In conclusion, the present network meta-analysis suggested that for a decreased mortality due to variceal rebleeding in patients with cirrhosis, nadolol plus ISMN may be a preferable choice, while ES is associated with a higher risk of unfavourable treatment outcomes. Further well-controlled studies are required to further elucidate the appropriate treatment options.

AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis

“…True failure of primary prophylaxis with NSBB (propranolol or nadolol) is associated with a persistently high risk of rebleeding and death despite addition of EVL 199 for secondary prophylaxis. In such patients, one may consider adding isosorbide mononitrate, 200 switching the NSBB to carvedilol given its greater portal pressure-reducing effect, 197 or consider adding simvastatin to NSBB and EVL, a strategy that in a single RCT was associated with reduced mortality despite no effect on variceal rebleeding 33,34 . Simvastatin should be used with caution in patients with total bilirubin >3 mg/dL and used only at low doses (10–20 mg/day) in patients with CTP B–C because of the risk of rhabdomyolysis 38 …”