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Therapeutics |

Nadolol and isosorbide prevented recurrent variceal bleeding better than did endoscopic ligation in cirrhosis

Hubert H. Nietsch, MD; and Kris V. Kowdley, MD
[+] Article, Author, and Disclosure Information

†Information provided by author.

Source of funding: In part, Fundació Investigació Sant Pau.

For correspondence: Dr. C. Villanueva, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. E-mail cvillanueva@santpau.es.*See Glossary.

Ann Intern Med. 2002;136(3):94. doi:10.7326/ACPJC-2002-136-3-094
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Question: In patients with cirrhosis hospitalized for esophageal variceal bleeding, is treatment with nadolol and isosorbide mononitrate more effective than endoscopic ligation for preventing recurrent bleeding?

Design: Randomized {allocation concealed*}†, {unblinded}†,* controlled trial with mean follow-up of 24 months.

Setting: A hospital in Barcelona, Spain.

Patients: 144 patients (mean age 59 y, 63% men) who had cirrhosis, were hospitalized for esophageal variceal bleeding, and had emergency endoscopy. Exclusion criteria included < 18 years of age, poor hepatic function, advanced hepatocellular carcinoma, and life expectancy ≤ 6 months. All patients were included in the analysis with 9 patients censored at the time of the last visit.

Intervention: 72 patients were allocated to combined medication with nadolol, 80 mg orally once daily, adjusted over 5 days to reduce the resting heart rate by 25% (but not lower than 55 beats/min), and oral isosorbide mononitrate, progressively increased over 1 week from 20 mg once daily at bedtime to 40 mg twice/d or to the maximal tolerated dose. 72 patients were allocated to endoscopic ligation with a single band with an overtube or a multiband device done after randomization, on day 7, and every 2 to 3 weeks until the varices were eradicated. Follow-up endoscopy was done at 3 months after eradication and every 6 months thereafter, and additional sessions of ligation were done, if required. In both groups, sclerotherapy or somatostatin, or both, were used for endoscopic control of acute hemorrhage during the index or recurrent bleeds.

Main outcome measures: Recurrent bleeding, complications, and mortality.

Main results: Analysis was by intention to treat and used Kaplan-Meier survival curves. The cumulative risk for recurrent bleeding was of borderline statistical significance between groups (P = 0.04) (Table). The cumulative risk for recurrent variceal bleeding was lower in the combined medication group than in the ligation group (Table). Fewer severe treatment-related complications occurred in the combined medication group than in the ligation group (3% vs 12%, P = 0.05), but groups did not differ for occurrence of overall complications (P = 0.71). Groups did not differ for cumulative risk for death (Table).

Conclusion: In patients with cirrhosis hospitalized for esophageal variceal bleeding, treatment with nadolol and isosorbide mononitrate prevented recurrent variceal bleeding more effectively than did endoscopic ligation.

Nadolol and isosorbide mononitrate (medication) vs endoscopic ligation for esophageal variceal bleeding in cirrhosis‡

Outcomes at mean 24 moMedicationLigationRRR (95% CI)NNT (CI)
Risk for recurrent bleeding33%49%23% (−2 to 52)Borderline significance
Risk for recurrent variceal bleeding28%44%33% (8 to 53)7 (5 to 30)
Risk for death32%42%15% (−13 to 38)Not significant

‡Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data provided by author.





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