1. GASTROENTEROLOGY 2009;137:892–901
R2. 정 회 훈

2. Background
The lifetime prevalence of varices in cirrhotics : 80% ~ 90%
Variceal bleeding : 30% ~ 40%
The mortality of acute variceal hemorrhage : 15% ~ 20%
Risk of variceal rebleeding at 1 year : 60% ~ 80%
Baveno IV consensus for prevention of rebleeding in cirrhotics
 β-blockers or endoscopic variceal ligation or both
Conceptually, reduction of portal pressure by combination
pharmacotherapy and local obliteration of varices
should be more effective and synergistic than either therapy
administered alone.
whether a combination of EVL and propranolol/ISMN
was more effective than EVL alone for secondary prophylaxis.

3. Patients and Methods Exclusion criteria Patients
History of hematemesis and/or melena
Proven esophageal varices as the bleeding source on GI endoscopy
Exclusion criteria
History of endoscopic sclerotherapy, EVL, or cyanoacrylate Injection
History of surgery for portal hypertension
Coexisting malignancy
Severe cardiopulmonary or renal disease
History of severe adverse effects or contraindications to β-blockers
(bronchial asthma, uncontrolled DM, heart failure, complete heart block
Peripheral vascular disease, prostatic hypertrophy
SBP< 100 mm Hg, HR< 55/min )
Refusal to give consent to participate in the trial

4. Size of esophageal varices  Conn’s classification
Baseline Evaluation
Cirrhotic patients
Determine the etiology
Severity in cirrhotics : Child–Turcotte–Pugh (CPT) score
Non-cirrhotic patients
Non-cirrhotic portal fibrosis
Extrahepatic portal vein obstruction
Size of esophageal varices  Conn’s classification
Hepatic Venous Pressure Gradient Measurement
Measured before randomization
Wedged hepatic venous pressure - free hepatic venous pressure
Normal value : 1 ~ 4 mmHg
Randomization
Open-label, randomized controlled trial, after HVPG
EVL or EVL plus drugs
Conn’s classification
grade 1 : visible only during 1 phase of respiration
or valsalva maneuver;
grade 2 : visible during both phases of respiration
grade 3 : 3 ~ 6 mm
grade 4 : >6 mm

5. Endoscopic Variceal Ligation
Variceal band ligation at the first endoscopy session within 24 hours
EVL was done at intervals of 3–4 weeks
 completely obliterated or reduced to grade 1 size
Repeat endoscopy : monthly intervals for 3 months and
then at 3-month intervals (recurrent vaices)
Pantoprazole (40 mg twice a day) + Sucralfate (4 times per day)
Ascites were prescribed oral antibiotics
Correct the coagulation disorders
EVL Plus Drug Therapy
Propranolol
Within 24 hours, after a baseline ECG and cardiac evaluation
40 mg twice a day  320mg/day (dose up : 20 to 40 mg/day)
HR > 55 beats
Isosorbide mononitrate (ISMN)
After attaining a stable dose of propranolol
10 mg twice a day  40mg/day (dose up :10–20 mg/day )

6. End Points Bleeding Primary end points : bleeding and death
Secondary end points : complications, serious adverse effects,
upper GI tract bleeding (not related to portal hypertension)
Bleeding
Upper GI endoscopy within 12 hours
Baveno IV consensus conference criteria
Bleeding from
: Esophageal varices
Gastric varices
Portal hypertensive gastropathy
Esophageal ulcer as a result of band ligation
Significant Bleeding
: HR > 100 bpm, SBP <100 mmHg, postural drop > 20 mmHg,
transfusion requirement > 2U
Terlipressin or somatostatin : continued for 5 days

7. Results

8. Table 1. Baseline Characteristics of Study Groups
85%
15%

9. Table 2. Primary and Secondary End Points

10. Figure 1. Kaplan–Meier graph showing cumulative probability of rebleed
31%
27%
P=0.822
Figure 1. Kaplan–Meier graph showing cumulative probability of rebleed
in the 2 groups, in all patients.

11. Figure 2. Kaplan–Meier graph showing cumulative probability of death 4% 2%
P=0.682
Figure 2. Kaplan–Meier graph showing cumulative probability of death
in the 2 groups, in all patients.

12. Figure 3. Kaplan–Meier graph showing cumulative probability of rebleed
30%
24%
P=0.720
Figure 3. Kaplan–Meier graph showing cumulative probability of rebleed
in the 2 groups, in the subgroup analysis of cirrhotic patients.

13. Table 2. Primary and Secondary End Points
Propranolol :
Dizziness : 2
Hypotension : 2
Dyspnea : 1
ISMN :
Headache : 4
51 (58%)
46 (52%)
P=0.879
40 (45%)
48 (54%)
P=0.041

14. Table 3. Predictors of Rebleed

15. Table 4. Relative Risks of Factors Found to Be Significant Predictors of Rebleed on the Univariate Analysis
Table 5. Factors Predictive of Rebleed on Multivariate Analysis

16. Conclusion EVL alone is sufficient to prevent variceal rebleeding
in patients with history of variceal bleeding.
Addition of propranolol and ISMN to EVL
does not reduce the incidence of variceal rebleeding
but increases severe adverse effects.
Risk factors for rebleeding include ascites, low serum
albumin, and high hepatic venous pressure gradients.