Villanueva C, Miñana J, Ortiz J, et al. Endoscopic ligation compared with combined treatment with nadolol and isosorbide monitrate to prevent recurrent variceal bleeding. N Engl J Med 2001;345:647-55
Major Findings
-- 144 patients with variceal bleeding were randomized to banding only vs. non-selective B-blockers and nitrates only.
-- Banding was done at randomization, 7 days and every 2 to 3 weeks.
-- Non-selective B blocker (Nadolol) was started at a dose of 80 mg per day to decrease resting heart rate by 25% but not below 55 bpm.
-- Oral isosorbide mononitrate was started at 20mg once a day and titrated to 40 mg twice a day if possible.
-- Patients with advanced cirrhosis (Child’s-Pugh >12) were excluded
-- Both groups were comparable in regards to age, severity of cirrhosis and etiology. The majority were Child’s Pugh class B. Lost to follow-up and # of alcoholics becoming abstinent were similar in both groups.
-- Probability of recurrent bleeding was lower in the medication group (p=0.04). Among Child’s A risk of rebleeding on medication vs. ligation was 21% vs. 43% (p=0.05), Child’s B: 33% vs. 50% (p=0.64) and Child’s C: 53% vs. 63% (p=0.64)
-- 9/72 had complications from banding: esophageal ulcers with bleed, aspiration pneumonia
-- 2/72 had complications from medications: dyspnea and bradycardia
-- Nitrates did not trigger ascites
-- There was no difference in mortality
FACTS TO REMEMBER FOR BOARDS
- Recurrent bleeding after first variceal bleeding episode is >50%
-- The use of nitrates is not recommended for patients with advanced cirrhosis
-- Reduction of hepatic venous gradient to <12 mmHg or >20% from baseline is required to decrease risk of recurrent variceal bleeding.
-- Non-selective B-blockers constrict splachnic circulation, decrease portal perfusion. Nitrates dilate intra-hepatic arterial bed.
-- It is believed that isosorbide mononitrate is more effective than isosorbide dinitrate in lowering portal pressures
Comments
) The results were barely statistically significant, were non-significant for Child’s B and C patients
) In practice, compliance with B-blockers and nitrates is poor, as is return visit for ligation
) For patients that refuse, dislike or are difficult to endoscope, combination therapy may be a useful alternative
) Doses of beta blockers and nitrates used in this study are higher than we use in practice