Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers.
OBJECTIVE
Nonselective beta-blockers (beta-blockers) are very effective in preventing first variceal bleeding (FVB) in patients with cirrhosis. However, 15%-25% of patients have contraindications or develop severe side effects precluding its use. The present study evaluates whether isosorbide-5-mononitrate (Is-MN) effectively prevents variceal bleeding in patients with contraindications or who could not tolerate beta-blockers.


METHODS
One hundred thirty-three consecutive cirrhotic patients with gastro-esophageal varices and contraindications or intolerance to beta-blockers were included in a multicenter, prospective, double-blind randomized controlled trial. Sixty-seven were randomized to receive Is-MN, and 66 to receive placebo.


RESULTS
There were no significant differences in the 1- and 2-year actuarial probability of experiencing a FVB between the 2 treatment groups. Presence of variceal red signs at endoscopy was the only variable independently associated with an increased risk of variceal bleeding on follow-up (relative risk 3.4; P < 0.01). Survival and adverse events were similar in the 2 groups. There were no significant differences in the incidence of ascites or changes in renal function.


CONCLUSIONS
Is-MN does not reduce the incidence of FVB in patients with cirrhosis and esophageal varices who cannot be treated with beta-blockers because contraindications or intolerance to these drugs, suggesting that Is-MN has no place in the primary prophylaxis of variceal bleeding.
García-Pagán
J C
JC
Hepatic Hemodynamic Laboratory, Liver Unit, IMD, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain. jcgarcia@clinic.ub.es
Villanueva
C
C
Vila
M C
MC
Albillos
A
A
Genescà
J
J
Ruiz-Del-Arbol
L
L
Planas
R
R
Rodriguez
M
M
Calleja
J L
JL
González
A
A
Solà
R
R
Balanzó
J
J
Bosch
J
J
D000319:Adrenergic beta-Antagonists; D001201:Ascites / Q000503:physiopathology; D000075202:Contraindications; D004311:Double-Blind Method; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008103:Liver Cirrhosis / Q000145:classification / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D011336:Probability; D011517:Prothrombin Time; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate