Primary prophylaxis of variceal hemorrhage: a randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate.
OBJECTIVE
This randomized controlled trial compared variceal band ligation (VBL), propranolol (PPL), and isosorbide-5-mononitrate (ISMN) in the prevention of first esophageal variceal bleed.


METHODS
Over a 6-year period, 172 patients with cirrhosis, grade II or III esophageal varices that had never bled, were recruited; 44 into VBL, 66 into PPL, and 62 into ISMN. Baseline patient characteristics: age, 55 +/- 11 years; Child-Pugh score, 8 +/- 2; 65% alcohol-induced cirrhosis; follow-up period, 19.7 +/- 17.6 months (range, 0.13-72.1 months), were comparable in the 3 groups.


RESULTS
On intention-to-treat analysis, variceal bleeding occurred in 7% of patients randomized to VBL, 14% to PPL, and 23% to ISMN. The 2-year actuarial risks for first variceal bleed were 6.2% (95% confidence interval [CI], 0.0%-15.0%) for VBL, 19.4% (95% CI, 0.1%-32.4%) for PPL, and 27.7% (95% CI, 14.2%-41.2%) for ISMN. A significant number of patients reported side effects with drug treatment (45% PPL and 42% ISMN vs. 2% VBL; P = 0.00), resulting in withdrawal from treatment in 30% of PPL and 21% of ISMN patients. There were no statistically significant differences in mortality rates in the 3 groups. In as-treated analysis, there was a statistically significant difference in actuarial risk for bleeding at 2 years between VBL and ISMN (7.5%, 95% CI, 2.5%-10.6% vs. 33.0%, 95% CI, 15%-49%, respectively, log rank test P = 0.03) but not between VBL and PPL.


CONCLUSIONS
VBL was equivalent to PPL and superior to ISMN in preventing first variceal bleed. The side-effect profile for pharmacotherapy was considerable.
Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh, Scotland.
Hock F
HF
Lui
Adrian J
AJ
Stanley
Ewan H
EH
Forrest
Rajiv
R
Jalan
W Stuart
WS
Hislop
Peter R
PR
Mills
Niall D C
ND
Finlayson
Alastair J
AJ
Macgilchrist
Peter C
PC
Hayes
D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004932:Esophageal and Gastric Varices / Q000628:therapy*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D008026:Ligation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D011433:Propranolol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate