Correspondence

Prevention of Recurrent Variceal Bleeding

N Engl J Med 2002; 346:209-210January 17, 2002

Article

To the Editor:

Villanueva et al. (Aug. 30 issue)1 compared two treatments for recurrent bleeding from esophageal varices: endoscopic ligation and combined therapy with nadolol and isosorbide mononitrate. The initial dose of nadolol was 80 mg per day, and the mean (±SD) dose was 96±56 mg per day. In a review article in the same issue,2 Sharara and Rockey state that the initial dose of nadolol is 20 mg per day and the maximal dose is 80 mg per day. How many patients in the study by Villanueva et al. received doses of nadolol of more than 80 mg per day? Did higher nadolol doses correlate with improved outcomes? What doses do Villanueva et al. recommend for clinical practice?

David M. Novick, M.D.
Digestive Specialists, Kettering, OH 45429-3556
novdel@aol.com

2 References

1. 1

   Villanueva C, Minana J, Ortiz J, et al. Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding. N Engl J Med 2001;345:647-655
   Full Text | Web of Science | Medline

2. 2

   Sharara AI, Rockey DC. Gastroesophageal variceal hemorrhage. N Engl J Med 2001;345:669-681
   Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: For the treatment of portal hypertension, the dose of beta-blockers is usually individualized to achieve a 25 percent reduction in the resting heart rate or a rate of about 55 beats per minute.1 The initial dose of nadolol is usually 40 to 80 mg per day,2,3 and the dose is gradually increased. However, there is no relation between the development of variceal bleeding and the degree of beta-blockade as assessed by measurement of the heart rate.1 Hemodynamic measurements provide a more suitable way of monitoring patients at risk for variceal bleeding.4,5 A decrease in the hepatic venous pressure gradient to below 12 mm Hg or a decrease of more than 20 percent from base line is associated with significant protection against variceal hemorrhage and a reduced risk of death.4,5 In our study, 51 patients (71 percent) received 80 mg or more of nadolol per day, and the mean dose was higher among patients with a hemodynamic response than among those with no response (mean [±SD], 124±59 vs. 75±56 mg; P=0.005). Our findings further support the value of hemodynamic monitoring.

Càndid Villanueva, M.D.
Josep Miñana, M.D.
Joaquim Balanzo, M.D.
Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
cvillanueva@hsp.santpau.es

5 References

1. 1

   De Franchis R. Updating consensus in portal hypertension: report of the Baveno III Consensus Workshop on definitions, methodology and therapeutic strategies in portal hypertension. J Hepatol 2000;33:846-852
   CrossRef | Web of Science | Medline

2. 2

   Gatta A, Merkel C, Sacerdoti D, et al. Nadolol for prevention of variceal rebleeding in cirrhosis: a controlled clinical trial. Digestion 1987;37:22-28
   CrossRef | Web of Science | Medline

3. 3

   Lebrec D, Poynard T, Capron JP, et al. Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis: a randomized trial. J Hepatol 1988;7:118-125
   CrossRef | Web of Science | Medline

4. 4

   Groszmann RJ, Bosch J, Grace ND, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 1990;99:1401-1407
   Web of Science | Medline

5. 5

   Feu F, Garcia-Pagan JC, Bosch J, et al. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet 1995;346:1056-1059
   CrossRef | Web of Science | Medline