Endoscopic Variceal Ligation for Oesophageal Variceal Bleeding
Endoscopic Variceal Ligation for Oesophageal Variceal Bleeding
Background: The treatment effects of primary prophylactic endoscopic variceal ligation are unclear.
Aim: To compare the treatment effects of endoscopic variceal ligation and β -blockers for primary prophylaxis of oesophageal variceal bleeding. In addition, a subgroup analysis was done with the purpose to delineate differences in the effects of intervention that were biologically based.
Methods: We performed a literature search for randomized controlled trials, which compared the treatment effects of endoscopic variceal ligation with β -blockers for primary prophylaxis of oesophageal variceal bleeding. Of the 955 articles screened, eight randomized-controlled trials including 596 subjects (285 with endoscopic variceal ligation and 311 with β -blockers) were analysed. Outcomes measures evaluated were first gastrointestinal bleed, first variceal bleed, all-cause deaths, bleed-related deaths and severe adverse events. The measure of association employed was relative risk; with heterogeneity and sensitivity analyses.
Results: Variceal obliteration was obtained in 261 (91.6%) patients and target β -blockers therapy was achieved in 294 (94.5%) patients ( P = 0.19). Endoscopic variceal ligation compared with β -blockers significantly reduced rates of first gastrointestinal bleed by 31% (RR, 0.69; 95% CI: 0.49–0.96; P = 0.03; NNTB = 15) and first variceal bleed by 43% (RR, 0.57; 95% CI: 0.38–0.85; P = 0.0067; NNTB = 11). All-cause deaths and bleed-related deaths were unaffected (RR, 1.03; 95% CI: 0.79–1.36; P = 0.81 and RR, 0.84; 95% CI: 0.44–1.61; P = 0.60 respectively). Severe adverse events were significantly less in endoscopic variceal ligation compared with β -blockers (RR, 0.34; 95% CI: 0.17–0.69; P = 0.0024; NNTB = 28). Sensitivity analysis of five trials published in peer review journals and four trials with high quality showed results similar to those seen in the primary analysis of all the eight trials, confirming stability of conclusions. Following variceal obliteration with endoscopic variceal ligation, oesophageal varices recurred in 83 (29.1%) patients. Seven (28.1%) patients bled with one fatal outcome. In subgroup analyses, endoscopic variceal ligation had significant advantage compared wtih β -blockers in trials including ≤30% patients with alcoholic cirrhosis, >30% patients with Child Class C cirrhosis and >50% patients with large varices.
Conclusions: In patients with cirrhosis with moderate to large varices and who have not bled, endoscopic varices ligation compared with β -blockers significantly reduced bleeding episodes and severe adverse events, but had no effect on mortality.
In patients with cirrhosis, the prevalence of oesophageal varices is 60% and the risk of gastrointestinal bleeding is approximately 30%. High risk factors for first haemorrhage include the severity of cirrhosis, the size of oesophageal varices and the presence of red signs on varices. About 30–50% of patients admitted for the first episode of variceal bleeding die within 6 weeks. Accordingly, 10–15% of untreated and unselected patients with cirrhosis die from a first episode of gastrointestinal bleeding. These findings strongly suggest that prophylaxis should be implemented to prevent first gastrointestinal bleeding, especially in patients with a high risk of haemorrhage.
Non-selective β-adrenergic antagonists namely propranolol and nadolol, are widely used in the prevention of first bleeding in patients with cirrhosis and portal hypertension. These drugs reduce the relative risk (RR) of bleeding by approximately 45% and the mortality rate by 20% at 2 years. However, β-blockers (BB) have several disadvantages for long-term therapy. About over one-third of patients do not exhibit decrease in portal pressure despite adequate β-blockade. This is important as protection afforded by BB depends on the degree of portal pressure reduction. Other problems include several contraindications, frequent adverse events necessitating withdrawal of therapy, need for long-term therapy and the risk of rebound bleeding upon abrupt cessation of therapy. Transjugular intrahepatic portosystemic shunts (TIPS) and endoscopic sclerotherapy are more effective than drug therapy but at the price of higher side-effects and, in some studies, higher mortality.
Because of its efficacy and safety, endoscopic variceal ligation (EVL) has become the method of choice for secondary prophylaxis of variceal bleeding. As a result of this favourable experience, there has been interest in extending use of EVL to the primary prophylaxis of oesophageal variceal bleeding. A meta-analysis of four randomized trials comparing EVL with BB for primary prevention of variceal bleeding revealed inconclusive results.
The purpose of this study was to perform a meta-analysis of randomized-controlled trials (RCT) comparing EVL with BB for primary prevention of variceal bleeding and determine the effect of EVL on first gastrointestinal bleed, all-cause deaths, bleed-related deaths and severe adverse events. In addition, a subgroup analysis was done with the purpose to delineate differences in the effects of intervention that were biologically based.
Background: The treatment effects of primary prophylactic endoscopic variceal ligation are unclear.
Aim: To compare the treatment effects of endoscopic variceal ligation and β -blockers for primary prophylaxis of oesophageal variceal bleeding. In addition, a subgroup analysis was done with the purpose to delineate differences in the effects of intervention that were biologically based.
Methods: We performed a literature search for randomized controlled trials, which compared the treatment effects of endoscopic variceal ligation with β -blockers for primary prophylaxis of oesophageal variceal bleeding. Of the 955 articles screened, eight randomized-controlled trials including 596 subjects (285 with endoscopic variceal ligation and 311 with β -blockers) were analysed. Outcomes measures evaluated were first gastrointestinal bleed, first variceal bleed, all-cause deaths, bleed-related deaths and severe adverse events. The measure of association employed was relative risk; with heterogeneity and sensitivity analyses.
Results: Variceal obliteration was obtained in 261 (91.6%) patients and target β -blockers therapy was achieved in 294 (94.5%) patients ( P = 0.19). Endoscopic variceal ligation compared with β -blockers significantly reduced rates of first gastrointestinal bleed by 31% (RR, 0.69; 95% CI: 0.49–0.96; P = 0.03; NNTB = 15) and first variceal bleed by 43% (RR, 0.57; 95% CI: 0.38–0.85; P = 0.0067; NNTB = 11). All-cause deaths and bleed-related deaths were unaffected (RR, 1.03; 95% CI: 0.79–1.36; P = 0.81 and RR, 0.84; 95% CI: 0.44–1.61; P = 0.60 respectively). Severe adverse events were significantly less in endoscopic variceal ligation compared with β -blockers (RR, 0.34; 95% CI: 0.17–0.69; P = 0.0024; NNTB = 28). Sensitivity analysis of five trials published in peer review journals and four trials with high quality showed results similar to those seen in the primary analysis of all the eight trials, confirming stability of conclusions. Following variceal obliteration with endoscopic variceal ligation, oesophageal varices recurred in 83 (29.1%) patients. Seven (28.1%) patients bled with one fatal outcome. In subgroup analyses, endoscopic variceal ligation had significant advantage compared wtih β -blockers in trials including ≤30% patients with alcoholic cirrhosis, >30% patients with Child Class C cirrhosis and >50% patients with large varices.
Conclusions: In patients with cirrhosis with moderate to large varices and who have not bled, endoscopic varices ligation compared with β -blockers significantly reduced bleeding episodes and severe adverse events, but had no effect on mortality.
In patients with cirrhosis, the prevalence of oesophageal varices is 60% and the risk of gastrointestinal bleeding is approximately 30%. High risk factors for first haemorrhage include the severity of cirrhosis, the size of oesophageal varices and the presence of red signs on varices. About 30–50% of patients admitted for the first episode of variceal bleeding die within 6 weeks. Accordingly, 10–15% of untreated and unselected patients with cirrhosis die from a first episode of gastrointestinal bleeding. These findings strongly suggest that prophylaxis should be implemented to prevent first gastrointestinal bleeding, especially in patients with a high risk of haemorrhage.
Non-selective β-adrenergic antagonists namely propranolol and nadolol, are widely used in the prevention of first bleeding in patients with cirrhosis and portal hypertension. These drugs reduce the relative risk (RR) of bleeding by approximately 45% and the mortality rate by 20% at 2 years. However, β-blockers (BB) have several disadvantages for long-term therapy. About over one-third of patients do not exhibit decrease in portal pressure despite adequate β-blockade. This is important as protection afforded by BB depends on the degree of portal pressure reduction. Other problems include several contraindications, frequent adverse events necessitating withdrawal of therapy, need for long-term therapy and the risk of rebound bleeding upon abrupt cessation of therapy. Transjugular intrahepatic portosystemic shunts (TIPS) and endoscopic sclerotherapy are more effective than drug therapy but at the price of higher side-effects and, in some studies, higher mortality.
Because of its efficacy and safety, endoscopic variceal ligation (EVL) has become the method of choice for secondary prophylaxis of variceal bleeding. As a result of this favourable experience, there has been interest in extending use of EVL to the primary prophylaxis of oesophageal variceal bleeding. A meta-analysis of four randomized trials comparing EVL with BB for primary prevention of variceal bleeding revealed inconclusive results.
The purpose of this study was to perform a meta-analysis of randomized-controlled trials (RCT) comparing EVL with BB for primary prevention of variceal bleeding and determine the effect of EVL on first gastrointestinal bleed, all-cause deaths, bleed-related deaths and severe adverse events. In addition, a subgroup analysis was done with the purpose to delineate differences in the effects of intervention that were biologically based.