Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy.
BACKGROUND
Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to beta-blockers +/- nitrates has not been clarified.


OBJECTIVE
To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation.


METHODS
Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy (n = 30) or nadolol + ligation (n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study.


RESULTS
Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN (P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group (P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group (P < 0.01), but not in the nadolol + ligation group (P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group (P = 0.05). The incidence of complications was similar.


CONCLUSIONS
In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders.
Villanueva
C
C
Gastrointestinal Bleeding Unit, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain. cvillanueva@santpau.es
Aracil
C
C
Colomo
A
A
Lopez-Balaguer
J M
JM
Piqueras
M
M
Gonzalez
B
B
Torras
X
X
Guarner
C
C
Balanzo
J
J
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D004932:Esophageal and Gastric Varices / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008026:Ligation / Q000379:methods*; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009248:Nadolol / Q000008:administration & dosage* / Q000009:adverse effects; D055502:Secondary Prevention; D014690:Venous Pressure / Q000187:drug effects
D000959:Antihypertensive Agents; D009248:Nadolol; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate