Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy
We conducted a prospective randomized
compared to a control group, in the prevention included,
study to evaluate the effectwness
of patienls according to Child-Pugh
lol was given twice daily with a mean final dose of 54 t 26 + 7%.
mean follow up of 19 f rebleeding 45-82);
f’nd paints were rebleeding or death. During
92% (95% Cl: 76-98);
the% differences were not statistically sigmficant.
patients, war an independent
and C, 38%. Proprano-
percentages of patients free of sclerotherapy,
these differences did not reach statistical significance.
ages of patients alive at 1 year were: propranolol, 81% (95%
classification was: A. 22%; 8.40%;
weekly using 1% polidocanol.
54% (95% CI: 36-71);
16 mglday, this resulted in a mean reduction in resting heart rate of
16 months, 43 patients bled and 22 patients died. The cumulative
at 1 year were: propranolol,
of variceal rebleeding in alcoholic cirrhotic patients. Among the 19 patients
The cumulative percent-
79% (95% Cl: 58-91):
which occurred in 66% of
predictive factor associated with a decreased risk of rehleeding or death. In conclusion, a life
table analysis of patients free of rebleeding.
as well as of patients surviving. revealed a tendency in favoor of propr;molol.
The lack of a statistical support for these two favorable
effects could he due to poor statistical power. Tbis latter might be
ascribed to a low level of bleeding and death rates due to study monitoring
in drinking habits was an in-
dependent significant predictive factor for bleeding and death
bleeding from esophageal vari-
ces is the main life threatening The prevention
consequence of cirrhosis.
of variceal rebleeding can be euiar
cal and include various procedures
the portal vein, or medical usingfi-blockers
Patients All adult alcoholic patients with arrhosis
unit for upper gastrointestinal
due to rup-
At the beginning of I98ds, the ef-
tured esophageal varices were considered for inclusian in
the study. Hemorrhage
bleeding or lowering the risk resub,
we began a prospective
study in 1983 to evaluate sclerotherapy
the effects of propranolol
on the rebleeding
pared to a control group.
ws defined as an hematemesia or
meiena which required
at least two units of blood.
tients were inc!uded if cirrhosis was confirmed tally or suggested by biochemical tients were younger
and clinical data, if pa-
than 75 years, if bleeding
crihed to esophageal vatices when varices bled actively.
and when there were recent signs of bleeding such 8s ad-
months in the first year and every 6 months thereafter.
hercnt clot or platelet aggregate or when esophageal vati-
each visit the patient‘s clinical condition was assessed and
ccs were the only lesion in the upper gastrointestinal with concomitant
presence of blood.
cludcd if they pre,rntcd or concomit.mt
o: a life
congestive gastropathy. bleeding
They were also excluded
if there ws nnother cause of upper gastrointestinal ing, gastric or duodenal
Patients were CX-
It hns been suggested that the
risk of these two lesion: might have been in-
creased by aclerotbcmpy.
if there was a contraindication
a blood sample was taken to perform a laboratory and alcohol level. Current In the propronolol
resting heart rate.
to the treatmenl
endoscopy and recurrem writes
the trial took place and did not known
or if +L
been given. Recruitment
of more then 6 units of blood
within the first 24 h to restore the haematocrit than 25% defining a severe bleeding).
Patients were also
(~.e., patients lo:1 to follow up) oc-
In patiens who rehled,
endoscopy was performed,
date ot !mtil
was defined in the s.une way as bleed-
ing prior to inclusion. gastrointestinal
bleeding or withdrawal
gave oral informed
31, 1988, i.e.,
year after the last patient started treatment.
1983. The cen-
excluded if they were expected to have a poor level of
The study protocol was approved by the local ethics
began in Janwy
soring date for the study was March
compliance or refused to participate.
assessing the outcome did not hclong 10 the center where
or any trratment
End points were either death or bk:eding. The person
been a previous course of sclsrotherapy to alter portal
was adrate by at
was assessed by
mediately treated by additional
patients were excluded to @blockers,
grouP, the dose of propranolol
drinking habtts were recoraed
justed, if necessary. in order to decrcnso hart
had been treated
of the hemorrhage:.
if pasaihle, to Patier.&
group had their trial medictltion
necessary. index vnriceal hleedittg was treated by conser-
patients received identical standard emergency treatment
It should be noted that, in 1982, our pol-
Glypressin or hal-
icy was not in favour of emergency endoscopic sclerother-
pending open the patient’s
assigned to treatment
series of sealed individual
using a consecutively opaque envelopes.
Patiects u’ere not blioded since the two treatment
dures were dlfferent,
was not given placebo. also not blinded.
Twice a day a conventional
dose of propranolol
was given and was titrated
caval shunt wa!: considered condition.
All bleeders were
up for 2 weeks following
the episode of rebleed-
the date of introduction
of the treatment
to prevent further rehleeding).
formulated until a 20
of sample size was based on a 1 year sponta-
to 25% reduction in resting heart rate occurred 6 h follow-
risk by 50%
ing drug administration
0.05 for n error,
or until the maximal
was used for active bleeding.
apy. As soon as bleeding stopped and systemic haemodybecame stable.
rate of 80% (2) and a reduction
selected a level of
and a level of 0.1 for @ error in a one-
dose had been dispessed. The daily starting dose of pro-
tailed test. 24 subjects would need to he included in each
40 mg and this was increased. as required,
16J mg. Sclerotherapy or GIF-IT
with either GlF-G
Olympus endoscopes. Patents
dared wth 5 to 10 ma diazepam. was paformed
were mildly se-
at the last 5 cm of the esophagus,
above the gastro-esophageal
rate, we would
group and a total of 75 patients. choosen for sample we armed trial (3).
Five ml of 1% poli-
the results should he cautiously
docanol were used for each injection,
and a total of 30 to
variables were compared
to a two-
Since a and ,r9 risks are underestimated,
45 ml was inlectcd per sessmn. Sclerotherapy
due to an estimated
need 26 patients
using 2 test, while Student’s
test or variance analysis were used for quantitative
ed at 5 to 7 day intervals unnl varices were no longer visi-
ables which were expressed as mean f
The method of life table analysis as described by
into the varix was usually avoided
presence of large ulcerations AI1 patients were submitted to follow up visits of every 3
and to the time unttl
one standard de-
to the patient’s
285 cuwes were compared using the log rank test. Data were analysed according to the intentionm-treat principle, that is. all randomized Pabents were analyrad. All p values are two tailed. In addition, a prognostic analysis was performed to account for Possslbleeffects of other variables on both rebleeding and death rae. In n first step, the predictive value of variables was evaluated in univariate analysis using log rank test for qualitative vatiables and likelihood raGa rest for quantitative variables. Then, variables with a p value