283

Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy

We conducted a prospective randomized

controlled

compared to a control group, in the prevention included,

the distribution

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%.

Sclerotherapy

was performed

mean follow up of 19 f rebleeding 45-82);

81%

(95%

Cl: 60-93);

f’nd paints were rebleeding or death. During

confidence

imerval

92% (95% Cl: 76-98);

the% differences were not statistically sigmficant.

patients, war an independent

and C, 38%. Proprano-

(Ct):

63-92);

sclerotherapy, Alcohol

the

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);

and sclerotherapy.

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,

control,

of propranolol

of variceal rebleeding in alcoholic cirrhotic patients. Among the 19 patients

64%

(95%

withdrawal,

Cl:

The cumulative percent-

79% (95% Cl: 58-91):

control,

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

since improvement

in drinking habits was an in-

dependent significant predictive factor for bleeding and death

Upper

gastrointestinal

bleeding from esophageal vari-

ces is the main life threatening The prevention

Patientsand Methods

consequence of cirrhosis.

of variceal rebleeding can be euiar

cal and include various procedures

surge-

of decompression

the portal vein, or medical usingfi-blockers

Patients All adult alcoholic patients with arrhosis

of

or endoscopic

ou

unit for upper gastrointestinal

admitled

hemorrhap

to

due to rup-

variceal sclerothempy.

At the beginning of I98ds, the ef-

tured esophageal varices were considered for inclusian in

ficacy

and sclerotherapy

the study. Hemorrhage

of propranolol

bleeding or lowering the risk resub,

of death

we began a prospective

study in 1983 to evaluate sclerotherapy

was debated.

randomized

and death

As a

controlled

the effects of propranolol

on the rebleeding

pared to a control group.

in preventing

and

rates com-

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

Pa-

bisroiogi-

and clinical data, if pa-

than 75 years, if bleeding

was ar-

crihed to esophageal vatices when varices bled actively.

2x3

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

wtb

hepatic rsrcinoma

1?enr (t.c.,Child-Pugh

expectancy under

scvcrc diwaw).

o: a life

Score >I3

congestive gastropathy. bleeding

(1)

They were also excluded

if there ws nnother cause of upper gastrointestinal ing, gastric or duodenal

tract

Patients were CX-

ulcer. gartrk

wices

hleed-

or severe

It hns been suggested that the

risk of these two lesion: might have been in-

creased by aclerotbcmpy.

Finally.

if there was a contraindication

a blood sample was taken to perform a laboratory and alcohol level. Current In the propronolol

Compliance

monitoring

resting heart rate.

there had

to the treatmenl

endoscopy and recurrem writes

the trial took place and did not known

or if +L

been given. Recruitment

had required

a transfusion

of more then 6 units of blood

within the first 24 h to restore the haematocrit than 25% defining a severe bleeding).

level (more

Patients were also

either death,

the censoring

If

identify

(~.e., patients lo:1 to follow up) oc-

In patiens who rehled,

endoscopy was performed,

the location

propranolol

date ot !mtil

was defined in the s.une way as bleed-

ing prior to inclusion. gastrointestinal

consem.

one

Patients were

until

bleeding or withdrawal

gave oral informed

31, 1988, i.e.,

year after the last patient started treatment.

curred. Rebleeding

Ail patients

had

1983. The cen-

followed

excluded if they were expected to have a poor level of

The study protocol was approved by the local ethics

hicb treatment

began in Janwy

soring date for the study was March

compliance or refused to participate.

committee.

were im-

assessing the outcome did not hclong 10 the center where

known

patient

who upper

injectlwtr.

or any trratment

haemodynamics,

patients

underwent

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

In addition,

with nclerotherap!

mediately treated by additional

patients were excluded to @blockers,

grouP, the dose of propranolol

least 20%.

gastrointestinal

profile

drinking habtts were recoraed

justed, if necessary. in order to decrcnso hart

had been treated

At

of the hemorrhage:.

an upper

if pasaihle, to Patier.&

group had their trial medictltion

in the

stopped.

All

necessary. index vnriceal hleedittg was treated by conser-

patients received identical standard emergency treatment

vative treatment

including intravenous

for

loon tamponade.

It should be noted that, in 1982, our pol-

Glypressin or hal-

icy was not in favour of emergency endoscopic sclerother-

rehleeding.

bleeding.

For

variceal

intravenous

oon tamponade

Clypressin

persisted,

namic conditions

pending open the patient’s

eligible

randomly

assigned to treatment

numbered

series of sealed individual

patients

were

using a consecutively opaque envelopes.

Patiects u’ere not blioded since the two treatment

proce-

dures were dlfferent,

group

and therefore,

was not given placebo. also not blinded.

ihe cornto,

Consequently,

physicians

Twice a day a conventional

dose of propranolol

was given and was titrated

a mesenteric

inactive

was administered.

Ball-

If hleeding

caval shunt wa!: considered condition.

de-

All bleeders were

followed

up for 2 weeks following

the episode of rebleed-

ing (i.e..

the date of introduction

of the treatment

aimed

to prevent further rehleeding).

were

formulated until a 20

Calculation

of sample size was based on a 1 year sponta-

neons rehleeding

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

and

was used for active bleeding.

apy. As soon as bleeding stopped and systemic haemodybecame stable.

hemorrhage

permitted

rate of 80% (2) and a reduction

with treatment.

Having

of that

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

pranololw86

group.

40 mg and this was increased. as required,

16J mg. Sclerotherapy or GIF-IT

was performed

with either GlF-G

Olympus endoscopes. Patents

dared wth 5 to 10 ma diazepam. was paformed

were mildly se-

Intravascular

sclerosine

at the last 5 cm of the esophagus,

above the gastro-esophageal

to

just

We further

10% drop-out

estimated

that,

rate, we would

group and a total of 75 patients. choosen for sample we armed trial (3).

in each

the formula

calculat~~~~ pertained

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

was repeat-

However,

to a two-

Since a and ,r9 risks are underestimated,

junction.

45 ml was inlectcd per sessmn. Sclerotherapy

due to an estimated

need 26 patients

interpreted.

Qualitative

using 2 test, while Student’s

test or variance analysis were used for quantitative

t

vari-

ed at 5 to 7 day intervals unnl varices were no longer visi-

ables which were expressed as mean f

ble. Injection

viation.

The method of life table analysis as described by

Kaplan

and Meier

into the varix was usually avoided

in the

presence of large ulcerations AI1 patients were submitted to follow up visits of every 3

time

was applied

and to the time unttl

one standard de-

to the patient’s

patients

mhled.

w&al Resulting

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

Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy.

We conducted a prospective randomized controlled study to evaluate the effectiveness of propranolol and sclerotherapy, compared to a control group, in...
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