Surgery

Beta-Blockers Alone May Be Preferred to Prevent First Variceal Bleeding

Use of beta-blockers alone without endoscopic variceal ligation (EVL) may be preferred for prophylaxis of first variceal bleeding, according to the results of a randomized trial reported in the July issue of Hepatology. "The strength of EVL lies in its ability to obliterate varices, but portal pressure may be elevated after repeated procedures," said lead author Gin-Ho Lo, MD, from the E-DA Hospital in Kaohsiung, Taiwan, in a news release. "Moreover, varices frequently recur after variceal obliteration achieved by EVL and beta blockers were documented to be able to reduce variceal recurrence. A combination of nadolol and EVL has been well established in preventing secondary variceal bleeding, but the effectiveness of this approach is unknown in preventing the first variceal bleeding."
The goal of the study was to assess the efficacy and safety of combining nadolol with ligation in cirrhotic patients who had high-risk esophageal varices but no history of bleeding. Participants were assigned to band ligation plus nadolol (combined group; n = 70) or to nadolol alone (nadolol group; n = 70). At baseline, both groups had similar clinical and demographic characteristics. Median duration of follow-up was 26 months.
Ligation treatment was administered with multiligators at an interval of 4 weeks until variceal obliteration was achieved. In both the combined group and the nadolol group, nadolol was given at a dose sufficient to lower the pulse rate by 25%.
Variceal obliteration was achieved by 50 patients (71%) in the combined group. Mean nadolol dose was 52 ± 16 mg in the combined group vs 56 ± 19 mg in the nadolol group.
Upper gastrointestinal tract bleeding occurred during follow-up in 18 patients (26%) in the combined group and in 13 patients (18%) in the nadolol group (P = NS). For esophageal variceal bleeding, the numbers were 10 (14%) and 9 (13%), respectively (P = NS).
There were 16 deaths in each group. In the combined group, 48 patients (68%) had adverse events vs 28 patients (40%) in the nadolol group (P = .06).
"Our findings indicated that the addition of ligation to nadolol may increase adverse events and does not enhance effectiveness in preventing first variceal bleeding," Dr. Lo said. "Previous meta analysis of trials found that severe adverse events were significantly less in EVL compared with beta blockers. Based on our observation, nadolol alone did not cause severe adverse events if nadolol was reduced or discontinued in patients who reported side effects. The value of EVL in combination therapy requires further investigation."
Limitations of this study are that 70% of patients were excluded from the study, mostly because of hepatocellular carcinoma and/or old age, and the variceal obliteration rate was 71%, which was slightly lower than 86% in the investigators' previous study.
"Beta blockers are still currently the treatment of choice for prophylaxis of first variceal bleeding," the study authors conclude. "...[O]ther than the treatment aimed at esophageal varices, treatment of the underlying etiology of cirrhosis, such as abstinence from alcohol in alcoholic cirrhotic patients and antiviral therapy in hepatitis B virus-related cirrhotic patients, is also important for improvement of survival. Lastly, these patients may require liver transplantation to alter the dismal outcome."
The study authors have disclosed no relevant financial relationships.