Prophylaxis Of First Variceal Bleeding Research Articles

Can Non-Selective Beta-Blockers (NSBBs) Prevent Enlargement of Small Esophageal Varices in Patients with Cirrhosis? A Meta-analysis

Non-selective beta-blockers (NSBBs) are recommended for prophylaxis of first variceal bleeding in patients of cirrhosis with large esophageal varices. However, the data is conflicting whether NSBBs can also prevent growth of small esophageal varices to large size. To perform a meta-analysis of the randomized clinical trials comparing NSBBs with placebo for prevention of development of large esophageal varices in patients of cirrhosis with small esophageal varices. The PubMed, EMBASE, Science Direct, and Cochrane library databases were searched for relevant papers. A meta-analysis was performed using risk ratios (RRs) with 95% confidence interval (CI) as the effect sizes. Overall, 314 trials were initially retrieved from the database searches, of which five randomized controlled trials were included in the meta-analysis. The incidence of development of large varices (RR=0.91, 95%CI: 0.29-2.86; P=0.87) was similar between NSBB and placebo groups. However, the heterogeneity among studies was significant (P<0.01) with an I2 of 93%. The incidences of first variceal bleeding (RR=0.72, 95%CI: 0.25-2.12; P=0.55) and death (RR=0.76, 95%CI: 0.50-1.15; P=0.19) were also similar between NSBB and placebo groups; with no heterogeneity. The incidence of adverse events was significantly higher in the NSBB group compared with the placebo group (RR=4.66, 95%CI: 1.36-15.91; P=0.01). The results of this meta-analysis indicate that NSBBs are not effective in preventing growth of small varices and may lead to significant adverse effects. Hence, NSBBs should not be recommended for cirrhotic patients with small varices.

Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding

Administration of nonselective beta-blockers in prophylaxis of first variceal bleeding is not suitable for all patients. Thus, we evaluated endoscopic variceal band ligation (EVBL) in primary prevention of bleeding in patients with cirrhosis and large esophageal varices. A total of 73 consecutive patients with liver cirrhosis and large esophageal varices without a history of gastrointestinal bleeding were randomized to receive either EVBL or propranolol and were followed for up to 18 months. Forty patients underwent EVBL and 33 patients received propranolol. Variceal bleeding occurred in 2 patients in the EVBL (5%) and in 2 patients in the propranolol group (6%, NS). The 18 month actuarial risk for first variceal bleed was 5% in the EVBL (95% CI, 0-12%) and 20% in the propranolol group (95% CI, 0-49%, NS). The actuarial probability of death at 18 months of follow-up was 5% (95% CI, 0-11%) in the EVBL group and 7% (95% CI, 0-17%, NS) in the propranolol arm. In conclusion, EVBL was an effective and safe alternative to propranolol in primary prophylaxis of bleeding in patients with large esophageal varices.

Controlled trial of ligation plus nadolol versus nadolol alone for the prevention of first variceal bleeding

Both nadolol and ligation have proved to be effective in the prophylaxis of first variceal bleeding. This study was conducted to evaluate the effects and safety of combining nadolol with ligation. Cirrhotic patients with high-risk esophageal varices but without a bleeding history were considered for enrolment. Eligible patients were randomized to receive band ligation plus nadolol (Combined group, 70 patients) or nadolol alone (Nadolol group, 70 patients). In the Combined group multiligators were applied. Patients received regular ligation treatment at an interval of 4 weeks until variceal obliteration. Nadolol was administered at a dose to reduce 25% of the pulse rate in both the Combined group and the Nadolol group. Both groups were comparable in baseline data. In the Combined group 50 patients (71%) achieved variceal obliteration. The mean dose of nadolol was 52 +/- 16 mg in the Combined group and 56 +/- 19 mg in the Nadolol group. During a median follow-up of 26 months, 18 patients (26%) in the Combined group and 13 patients (18%) in the Nadolol group experienced upper gastrointestinal bleeding (P = NS). Esophageal variceal bleeding occurred in 10 patients (14%) in the Combined group and nine patients (13%) in the Nadolol group (P = NS). Adverse events were noted in 48 patients (68%) in the Combined group and 28 patients (40%) in the Nadolol group (P = 0.06). Sixteen patients in each group died. The addition of ligation to nadolol may increase adverse events and did not enhance effectiveness in the prophylaxis of first variceal bleeding.

202 Endoscopic variceal band ligation in comparison with propranolol in prophylaxis of first variceal bleeding in patients with liver cirrhosis

202 Endoscopic variceal band ligation in comparison with propranolol in prophylaxis of first variceal bleeding in patients with liver cirrhosis

The use of endoscopic band ligation for the prophylaxis of variceal haemorrhage

The use of endoscopic band ligation for the prophylaxis of variceal haemorrhage

Randomised trial of nadolol alone or with isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis

The risk of having a first cirrhosis-associated variceal bleed is lowered by about 50% by beta-blockers. Use of beta-blockers is currently recommended for patients with cirrhosis and oesophageal varices that are at risk of bleeding. We aimed to test the effectiveness of isosorbide mononitrate as an adjunct to the beta-blocker nadolol in the prophylaxis of first variceal bleeding in these patients. We did a randomised multicentre study to compare the non-selective beta-blocker, nadolol, with nadolol plus isosorbide mononitrate in 146 relatively well (Child-Pugh score < or = 11) patients who had oesophageal varices at risk of bleeding. Patients on nadolol alone received a single oral 40 mg daily dose. Every second day the dose was titrated to achieve 20-25% decrease in resting heart rate (maximum dose 160 mg daily). Patients receiving both drugs received nadolol as above then isosorbide mononitrate was added starting with 10 mg orally twice daily, which was increased to 20 mg unless hypotension or severe headache occurred. The main endpoint was the occurrence of variceal bleeding of any severity. Patients were followed up for up to 40 months. During the study period 11 of 74 patients from the nadolol alone group and four of 72 from the nadolol plus isosorbide mononitrate group had variceal bleeding (log-rank test p = 0.03). Cumulative risk of variceal bleeding was 18% in the nadolol group and 7.5% in the combined treatment group (95% CI for difference 1-25%). Two patients in each group had a non-variceal bleed related to portal hypertension. 14 patients from the nadolol only group and eight from the combined treatment group died during the study period (log-rank test p = 0.09). Four and eight patients, respectively, had to discontinue one of the drugs because of side-effects. Nadolol plus isosorbide mononitrate is significantly more effective than nadolol alone in the primary prophylaxis of variceal bleeding in relatively well patients with cirrhosis, and has few side-effects.

A multicenter controlled study comparing beta-blockers and beta-blockers plus nitroderivatives in the primary prophylaxis of first variceal bleeding in cirrhosis: Interim analysis

A multicenter controlled study comparing beta-blockers and beta-blockers plus nitroderivatives in the primary prophylaxis of first variceal bleeding in cirrhosis: Interim analysis

Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding.

Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis, screening for oesophageal varices might be appropriate. We prospectively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months. At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1. The subsequent percentages of patients without large oesophageal varices were 74% at one year and 52% at two years. Univariate analysis showed that a longer duration of cirrhosis (p less than 0.05) and grade 1 oesophageal varices at entry (p less than 0.001) were predictive factors for the occurrence of large oesophageal varices, whereas, multivariate analysis showed that the initial size of the oesophageal varices (p less than 0.001), a high initial Child-Pugh score, and a smaller improvement in Child-Pugh score during the study were independent risk factors. Among patients with grades 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31% and 70% respectively. We have calculated that, accepting a maximum risk of first bleeding of 10% without prophylactic treatment, a patient without oesophageal varices should be screened endoscopically every other year, while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy.

Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis.

Prophylaxis of bleeding from esophageal varices is a very tempting concept at first glance, especially under the assumption of a high mortality associated with first variceal hemorrhage. Up to now four different measures have been tried for prophylaxis: portacaval shunt operation, devascularization procedures, sclerotherapy, and drugs. With the exception of portacaval shunts, ongoing controlled trials show a weak trend toward reduction of variceal bleeding and prolongation of survival in selected patients with compensated cirrhosis and large varices. However, prophylaxis of first variceal bleeding must still be regarded as experimental and should be restricted to controlled clinical studies.