A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis.
OBJECTIVE
Beta-blockers are extensively used to prevent variceal bleeding in patients with large esophageal varices. It is not established if beta-blockers delay the growth of small varices.


METHODS
A total of 161 patients with cirrhosis and small esophageal varices (F1 according to the classification of Beppu et al.) without previous bleeding were enrolled. A total of 83 patients were randomized to nadolol (dose adjusted to decrease resting heart rate by 25%; mean dose given, 62 +/- 25 mg/day) and 78 to placebo. The principal end point was occurrence of large esophageal varices (F2 or F3 according to the classification of Beppu et al.). Endoscopic examination was performed after 12, 24, 36, 48, and 60 months of follow-up. Mean follow-up was 36 months.


RESULTS
The 2 groups were well matched for demographic and clinical characteristics. During the study period, 9 patients randomized to nadolol and 29 randomized to placebo had growth of esophageal varices. At the end of follow-up, the cumulative risk was 20% versus 51% (P < 0.001) (absolute risk difference, 31%; 95% confidence interval, 17%-45%). When possible confounding factors were taken into account, treatment was a significant factor predicting growth of varices (odds ratio, 4.0; 95% confidence interval, 1.95-8.4). The cumulative probability of variceal bleeding was also lower in patients randomized to nadolol (P = 0.02). Survival was not different (P = 0.33). Adverse effects resulting in withdrawal of drug occurred in 9 in the nadolol group and one in the placebo group (P = 0.01).


CONCLUSIONS
This study suggests that beta-blocker prophylaxis of variceal bleeding in patients with compensated cirrhosis should be started when small esophageal varices are present.
Department of Clinical and Experimental Medicine, University of Padua, Padova, Italy. carlo.merkel@unipd.it
Carlo
C
Merkel
Renato
R
Marin
Paolo
P
Angeli
Pierluigi
P
Zanella
Martina
M
Felder
Elisabetta
E
Bernardinello
Giorgio
G
Cavallarin
Massimo
M
Bolognesi
Carlo
C
Donada
Barbara
B
Bellini
Pierluigi
P
Torboli
Angelo
A
Gatta
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D018572:Disease-Free Survival; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009248:Nadolol / Q000008:administration & dosage*; D010919:Placebos
D000319:Adrenergic beta-Antagonists; D010919:Placebos; D009248:Nadolol