Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT.
Nonselective beta-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide-5-mononitrate (IS-MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double-blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS-MN (n = 175). There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS-MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache. There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding.
García-Pagán
Juan Carlos
JC
Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malaties Digestives, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. jcgarcia@medicina.ub.es
Morillas
Rosa
R
Bañares
Rafael
R
Albillos
Agustin
A
Villanueva
Candido
C
Vila
Carme
C
Genescà
Joan
J
Jimenez
Manuel
M
Rodriguez
Manuel
M
Calleja
Jose Luis
JL
Balanzó
Joaquin
J
García-Durán
Fernando
F
Planas
Ramón
R
Bosch
Jaume
J
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004932:Esophageal and Gastric Varices / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007548:Isosorbide Dinitrate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011433:Propranolol / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016019:Survival Analysis; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D010919:Placebos; D014665:Vasodilator Agents; D011433:Propranolol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate