Journal»Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Whether beta-blockers (BB) or banding is the best therapy for primary prophylaxis of variceal bleeding is subject to debate. A randomized comparison between the 2 treatments was performed in candidates for liver transplantation (LT). A total of 62 patients with Child-Turcotte-Pugh B-C cirrhosis and high risk varices received propranolol (31) or variceal banding (31). The primary endpoint was variceal bleeding. There were 2 variceal hemorrhages (6.5%) in the banding group, related to postbanding ulcers, and 3 (9.7%) in the propranolol group (P = not significant [n.s.]). Deaths and bleeding related deaths were 3 and 1 for banding and 3 and 2 for BB, respectively (P = n.s.). A total of 14 patients underwent LT in the banding group and 10 in the propranolol group (P = n.s.). Adverse events were 2 postbanding ulcer bleedings in ligated patients (1 fatal) and 5 were intolerant to propranolol (P = n.s.). Mean costs per patient were higher with banding than with propranolol treatment (4,289 +/- 285 vs. 1,425 +/- 460 U.S. dollars, P < 0.001). In conclusion, propranolol and banding are similarly effective in reducing the incidence of variceal bleeding in candidates for LT, but ligation can be complicated by fatal bleeding and is more expensive. Our results suggest that banding should not be utilized as primary prophylaxis in transplant candidates who can be treated with BB.
BACKGROUND AND AIM: Bleeding varices is a major complication of liver cirrhosis; 30 70% may die from the effect of the first bleed. Primary prophylax~is is therefore an important therapeutic goal. The aim of this study is to compare Endoscopic Variceal Ligation (EVL) with medical treatment for the prevention of the first episode of variceal bleeding. METHODS: 156 cirrhotic patients with risky varices were prospectively randomized to receive either EVL (51 patients), propranolol (52 patients) or Isosorbid-5-Mono-Nitrate (ISMN) (53 patients). And follow-up for 18 24 months for bleeding episodes and or mortality. RESULTS: There was no statistically significant difference between the 3 groups as regard sex, age, Child score, etiology of cirrhosis and grade of varices. Bleeding occurred in 4 (7.5%) in EVL group, 18 (34.6%) in ISMN group and 13 (25.5%) in propranolol group. There was no difference in mortality when the 3 groups were compared (7.5% vs 11.5% vs 9.8%), P 0.78. Complications or side effects were reported in 28.3% in EVL compared to 34.6% with ISMN and 39.2% for propranolol. CONCLUSION: In patients with high risk esophageal varices, EVL is more effective and safer than propranolol which is more effective than ISMN for primary prophylaxis of variceal bleeding.
BACKGROUND AND AIM: To compare the efficacy and safety of endoscopic variceal ligation (EVL) with propranolol in prophylaxis on the rate of first esophageal variceal bleeding in patients with cirrhosis. METHODS: A prospective, randomized trial was conducted in 100 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. RESULTS: Life-table curves showed that prophylactic EVL and propranolol were similarly effective for primary prophylaxis of variceal bleeding (11/50 [22%]vs 12/50 [24%]; P = 0.68) and overall mortality (14/50 [28%]vs 12/50 [24%]; P = 0.49). The 2-year cumulative bleeding rate was 18% (9/50) in the EVL group and 16% (8/50) in the propranolol group. The 2-year cumulative mortality rate was 28% (14/50) in the EVL group and 24% (12/50) in the propranolol group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed no significant difference in mortality in both groups (P = 0.86). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. In the propranolol group, the mean daily dosage of the drug was 68.2 +/- 32.8 mg, which was sufficient to reduce the pulse rate by 25%. 20% of patients withdrew from propranolol treatment due to adverse events. CONCLUSIONS: Prophylaxis EVL is as effective and as safe as treatment with propranolol in decreasing the incidence of first variceal bleeding and death in cirrhotic patients with high-risk esophageal varices.
BACKGROUND & AIMS: Standard care for prevention of first esophageal variceal hemorrhage is beta-blockade, but this may be ineffective or unsafe. Our purpose was to compare endoscopic banding with propranolol for prevention of first variceal hemorrhage. METHODS: In a multicenter, prospective trial, 62 patients with cirrhosis with high-risk esophageal varices were randomized to propranolol (titrated to reducing resting pulse by > or =25%) or banding (performed monthly until varices were eradicated) and were followed up on the same schedule for a mean duration of 15 months. The primary end point was treatment failure, defined as the development of endoscopically documented variceal hemorrhage or a severe medical complication requiring discontinuation of therapy. Direct costs were estimated from Medicare reimbursements and fixed or variable charges for services up to treatment failure. RESULTS: Background variables of the treatment groups were similar. The trial was stopped early after an interim analysis showed that the failure rate of propranolol was significantly higher than that of banding (6/31 vs. 0/31; difference, 19.4%; P = .0098; 95% confidence interval for true difference, 6.4%-37.2%). Significantly more propranolol than banding patients had esophageal variceal hemorrhage (4/31 vs. 0/31; difference, 12.9%; P = .0443; 95% confidence interval for true difference, 0.8%-29%), and the cumulative mortality rate was significantly higher in the propranolol than in the banding group (4/31 vs. 0/31; difference, 12.9%; P = .0443; 95% confidence interval for true difference, 0.8%-29%). Direct costs of care were not significantly different. CONCLUSIONS: For patients with cirrhosis with high-risk esophageal varices and no history of variceal hemorrhage, propranolol-treated patients had significantly higher failure rates of failure, first esophageal varix hemorrhage, and cumulative mortality than banding patients. Direct costs of medical care were not significantly different.
Primary prophylaxis with nonselective beta-blockers in high-risk subjects has been shown to be effective in reducing both esophageal variceal bleeding and mortality. Recently it has been suggested that band ligation may be a better option for primary prophylaxis. We compared nonselective beta-blockers with band ligation in patients with large varices (F2, F3) and elevated hepatic venous wedge pressure gradient (HVWPG, > or = 12 mm Hg). All patients were prospectively followed for variceal bleeding, mortality, and treatment-related complications. Based on previous published studies, we estimated that 90 patients in each arm would be required to show a difference in bleeding rate. The study was prematurely terminated when we realized that our estimated sample size was inadequate to show a difference based on the observed bleeding rate. At the time of termination, 31 patients (Child A, 11; B, 14; C, 6), with a mean HVWPG of 19 +/- 9.1 mm Hg, were randomized to either band ligation (group A; n = 16) or beta-blockers (group B; n = 15). Baseline demographics of both groups were similar and the mean follow-up period was 27.4 +/- 12.9 months. During the follow-up, two patients in group A and one patient in group B had bleeding. Nine patients (29%; group A, six; group B, three; P = ns) died due to non-bleeding-related causes and five (16%) patients (group A, three; group B, two) underwent liver transplantation. Treatment-related complication were minimal in both groups. Despite the selection of high-risk patients, the observed bleeding rate was much lower than anticipated. Based on our observed bleeding rates, 424 patients would be required in each arm to show a difference between band ligation and beta-blocker therapy.
<b>OBJECTIVES: </b>Data in the literature regarding the role of endoscopic variceal ligation for the prevention of first variceal bleeding in cirrhotic patients are controversial. To further explore this issue we have compared ligation and propranolol treatment in a prospective randomized study.<b>METHODS: </b>Sixty patients with cirrhosis and oesophageal varices with no history but at high risk of bleeding were randomized to ligation treatment (30 patients) or propranolol (30 patients). Patients were followed for approximately 27.5 months.<b>RESULTS: </b>Variceal obliteration was achieved in 28 patients (93.3%) after 3+/-1 sessions. The mean daily dose of propranolol was 60.3+/-13.3 mg. Two patients (6.7%) in the ligation group and nine patients (30%) in the propranolol group developed variceal bleeding (P = 0.043). The actuarial risks of variceal bleeding at 2 years were 6.7% and 25%, respectively. On multivariate analysis, propranolol treatment and grade III varices turned out to be predictive factors for the risk of variceal bleeding. Mortality was not different between the two groups. There were no serious complications due to ligation. Propranolol treatment was discontinued in four patients because of side effects.<b>CONCLUSIONS: </b>Variceal ligation is a safe and more effective method than propranolol treatment for the prevention of first variceal bleeding in cirrhotic patients with high-risk varices.
In this randomized controlled multicenter trial, we compared endoscopic variceal banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of variceal bleeding. One hundred fifty-two cirrhotic patients with 2 or more esophageal varices (diameter >5 mm) without prior bleeding were randomized to VBL (n = 75) or PPL (n = 77). The groups were well matched with respect to baseline characteristics (age 56 +/- 10 years, alcoholic etiology 51%, Child-Pugh score 7.2 +/- 1.8). The mean follow-up was 34 +/- 19 months. Data were analyzed on an intention-to-treat basis. Neither bleeding incidence nor mortality differed significantly between the 2 groups. Variceal bleeding occurred in 25% of the VBL group and in 29% of the PPL group. The actuarial risks of bleeding after 2 years were 20% (VBL) and 18% (PPL). Fatal bleeding was observed in 12% (VBL) and 10% (PPL). It was associated with the ligation procedure in 2 patients (2.6%). Overall mortality was 45% (VBL) and 43% (PPL) with the 2-year actuarial risks being 28% (VBL) and 22% (PPL). 25% of patients withdrew from PPL treatment, 16% due to side effects. In conclusion, VBL and PPL were similarly effective for primary prophylaxis of variceal bleeding. VBL should be offered to patients who are not candidates for long-term PPL treatment.
BACKGROUND: The value of band ligation for prevention of the first episode of variceal bleeding has not been fully evaluated. This study compared the efficacy and safety of band ligation vs. treatment with a beta-blocker for the prophylactic prevention of first bleeding in patients with cirrhosis and high-risk esophageal varices. METHODS: A total of 100 patients with cirrhosis and endoscopically determined high-risk esophageal varices but no history of bleeding were randomized to band ligation (50 patients) or treatment with nadolol (50 patients). In the ligation group, two to 4 elastic bands were deployed during each session. Ligation was repeated at intervals of 3 to 4 weeks until variceal obliteration was achieved. In the nadolol group, the dose of the drug, administered once daily, was sufficient to reduce the pulse rate by 25%. RESULTS: In the ligation group, variceal obliteration was achieved in 41 patients (82%), at a mean of 2.7 (1.1) ligation sessions. In the nadolol group, the mean daily dose of nadolol administered was 60 (20) mg. During follow-up (median approximately 22 months), 10 patients (20%) in the ligation group and 16 (32%) in the nadolol group had upper-GI bleeding (p=0.23). Esophageal variceal bleeding occurred in 5 patients (10%) in the ligation group and 9 (18%) in the nadolol group (p=0.31). By multivariate Cox analysis, Child-Pugh class was the only factor predictive of variceal bleeding. Minor complications were noted in 9 patients (18%) in the ligation group and 4 (8%) in the nadolol group (p=0.35). No serious complication was encountered. Twelve patients in the ligation group and 11 in the nadolol group died (p=0.62). One patient in the ligation group and 3 in the nadolol group died from uncontrollable variceal hemorrhage. CONCLUSIONS: Variceal ligation is as effective and as safe as treatment with nadolol for prevention of first variceal bleeding in patients with cirrhosis.
BACKGROUND & AIMS: This randomized controlled trial compared variceal band ligation (VBL), propranolol (PPL), and isosorbide-5-mononitrate (ISMN) in the prevention of first esophageal variceal bleed. METHODS: Over a 6-year period, 172 patients with cirrhosis, grade II or III esophageal varices that had never bled, were recruited; 44 into VBL, 66 into PPL, and 62 into ISMN. Baseline patient characteristics: age, 55 +/- 11 years; Child-Pugh score, 8 +/- 2; 65% alcohol-induced cirrhosis; follow-up period, 19.7 +/- 17.6 months (range, 0.13-72.1 months), were comparable in the 3 groups. RESULTS: On intention-to-treat analysis, variceal bleeding occurred in 7% of patients randomized to VBL, 14% to PPL, and 23% to ISMN. The 2-year actuarial risks for first variceal bleed were 6.2% (95% confidence interval [CI], 0.0%-15.0%) for VBL, 19.4% (95% CI, 0.1%-32.4%) for PPL, and 27.7% (95% CI, 14.2%-41.2%) for ISMN. A significant number of patients reported side effects with drug treatment (45% PPL and 42% ISMN vs. 2% VBL; P = 0.00), resulting in withdrawal from treatment in 30% of PPL and 21% of ISMN patients. There were no statistically significant differences in mortality rates in the 3 groups. In as-treated analysis, there was a statistically significant difference in actuarial risk for bleeding at 2 years between VBL and ISMN (7.5%, 95% CI, 2.5%-10.6% vs. 33.0%, 95% CI, 15%-49%, respectively, log rank test P = 0.03) but not between VBL and PPL. CONCLUSIONS: VBL was equivalent to PPL and superior to ISMN in preventing first variceal bleed. The side-effect profile for pharmacotherapy was considerable.
Whether beta-blockers (BB) or banding is the best therapy for primary prophylaxis of variceal bleeding is subject to debate. A randomized comparison between the 2 treatments was performed in candidates for liver transplantation (LT). A total of 62 patients with Child-Turcotte-Pugh B-C cirrhosis and high risk varices received propranolol (31) or variceal banding (31). The primary endpoint was variceal bleeding. There were 2 variceal hemorrhages (6.5%) in the banding group, related to postbanding ulcers, and 3 (9.7%) in the propranolol group (P = not significant [n.s.]). Deaths and bleeding related deaths were 3 and 1 for banding and 3 and 2 for BB, respectively (P = n.s.). A total of 14 patients underwent LT in the banding group and 10 in the propranolol group (P = n.s.). Adverse events were 2 postbanding ulcer bleedings in ligated patients (1 fatal) and 5 were intolerant to propranolol (P = n.s.). Mean costs per patient were higher with banding than with propranolol treatment (4,289 +/- 285 vs. 1,425 +/- 460 U.S. dollars, P < 0.001). In conclusion, propranolol and banding are similarly effective in reducing the incidence of variceal bleeding in candidates for LT, but ligation can be complicated by fatal bleeding and is more expensive. Our results suggest that banding should not be utilized as primary prophylaxis in transplant candidates who can be treated with BB.
