Ligation versus propranolol for the primary prophylaxis of variceal bleeding in cirrhosis†

Abstract

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 longterm PPL treatment. (HEPATOLOGY 2004;40:65-72.) U pper intestinal hemorrhage is a common and often fatal complication of portal hypertension. It occurs in 30% of patients with cirrhosis, with each bleeding episode bearing a mortality risk of 30% to 50%. 1-3 Thus, prophylactic treatment prior to the first bleeding (i.e., primary prophylaxis) is mandatory in highrisk patients. 4,5 Nonselective ␤-blockers (i.e., propranolol, nadolol)-the current standard prophylaxis-reduce bleeding incidence and bleeding-related mortality. 6 -9 However, pharmacotherapy with ␤-blockers is not optimal: 30% to 40% of patients will not achieve a sufficient reduction of portal pressure to prevent bleeding. 10 -12 Furthermore, contraindications and side effects are common 13,14 and may require withdrawal, which reincreases the risk of bleeding. 15 Therefore, therapeutic alternatives to ␤-blockers are warranted. Due to heterogeneous results, prophylactic endoscopic sclerotherapy is not recommended for the primary prevention of variceal bleeding. 5,7 Compared to injection sclerotherapy, 16 variceal banding ligation (VBL) allows a more rapid and more effective eradication of varices with fewer side effects. 17 To date, only 2 trials comparing VBL with standard treatment (␤-blockers) have been fully published. 13,18 The results of these studies are controversial and partly inconclusive. In the present article, we report on the results of a prospective randomized multicenter trial comparing propranolol (PPL) and banding ligation for the primary prophylaxis of variceal bleeding in patients with cirrhosis.

Controlled Trial of Ligation Plus Nadolol Versus Nadolol Alone for the Prevention of First Variceal Bleeding

“…The first variceal bleeding and upper gastrointestinal bleeding rates were even slightly higher in patients receiving banding ligation as well as nadolol. The controlled trial with the largest sample size up to now, conducted by Schepke et al, 11 showed that variceal bleeding was 25% in the ligation group and 29% in the propranolol group. Compared with previous trials, our current figures of variceal bleed and upper gastrointestinal bleed in both groups were reasonable.…”

“…Compared with previous trials, our current figures of variceal bleed and upper gastrointestinal bleed in both groups were reasonable. [9][10][11][12] A total of 321 patients (70%) were excluded from the study. The majority of these excluded patients were due to the presence of hepatocellular carcinoma and old age.…”

“…8 Controlled studies that compared EVL with a beta blocker in the prevention of first variceal bleeding showed that EVL was at least equivalent to beta blockers in the prophylaxis of first variceal bleeding. [9][10][11][12] The strength of EVL lies in its ability to obliterate varices. However, the portal pressure may be elevated after repeated EVL.…”

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

“…Studies of VBL for primary prophylaxis that include patients with high-risk esophageal varices have shown that VBL significantly reduces the risk of first variceal bleeding and that serious adverse effects are uncommon [53][54][55][56][57]. A meta-analysis of five studies of VBL versus placebo suggested that VBL reduces the risk of first variceal bleed, bleeding-related mortality, and overall mortality [58].…”

“…Various published randomized trials comparing the efficacy and safety of VBL and b-blockers in primary prophylaxis exist [53][54][55][56][57][63][64][65][66][67]. A recent meta-analysis suggests that VBL has greater efficacy in preventing initial bleeding with a 34% relative risk reduction than do b-blockers.…”