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

doi:10.1016/0168-8278(91)90828-Y

Journal of Hepatology

Volume 12, Issue 3, May 1991, Pages 283-289

https://doi.org/10.1016/0168-8278(91)90828-Y Get rights and content

Abstract

We conducted a prospective randomized controlled study to evaluate the effectiveness of propranolol and sclerotherapy, compared to a control group, in the prevention of variceal rebleeding in alcoholic cirrhotic patients. Among the 79 patients included, the distribution of patients according to Child-Pugh classification was: A, 22%; B, 40%; and C, 38%. Propranolol was given twice daily with a mean final dose of 54 ± 16 mg/day, this resulted in a mean reduction in resting heart rate of 26 ± 7%. Sclerotherapy was performed weekly using 1% polidocanol. End points were rebleeding or death. During the mean follow up of 19 ± 16 months, 43 patients bled and 22 patients died. The cumulative percentages of patients free of rebleeding at 1 year were: propranolol, 81% (95% confidence interval (CI): 63–92); sclerotherapy, 64% (95% CI: 45–82); control, 54% (95% CI: 36–71); these differences did not reach statistical significance. The cumulative percentages of patients alive at 1 year were: propranolol, 92% (95% CI: 76–98); sclerotherapy, 79% (95% CI: 58–91); control, 81% (95% CI: 60–93); these differences were not statistically significant. Alcohol withdrawal, which occurred in 66% of patients, was an independent predictive factor associated with a decreased risk of rebleeding or death. In conclusion, a life table analysis of patients free of rebleeding, as well as of patients surviving, revealed a tendency in favour of propranolol. The lack of a statistical support for these two favorable effects could be due to poor statistical power. This latter might be ascribed to a low level of bleeding and death rates due to study monitoring since improvement in drinking habits was an independent significant predictive factor for bleeding and death.

References (30)

TB Reynolds et al.
Results of a 12 year randomized trial of portocaval shunt in patients with alcoholic liver disease and bleeding varices
Gastroenterology
(1981)
J Terblanche et al.
Failure of repeated injection sclerotherapy to improve long-term survival after oesophageal variceal bleeding. A five year prospective controlled clinical trial
Lancet
(1983)
PT Alexandrino et al.
Propranolol or endoscopic sclerotherapy in the prevention of recurrence of variceal bleeding
J Hepatol
(1988)
KW O'Connor et al.
Comparison of three nonsurgical treatments for bleeding esophageal varices
Gastroenterology
(1989)
TT Schubert et al.
Bleeding from varices in the gastric fundus complicating sclerotherapy
Gastrointest Endosc
(1989)
RNH Pugh et al.
Transection of the oesophagus for bleeding oesophageal varices
Br J Surg
(1973)
JT Casagrande et al.
An improved approximate formula for calculating sample sizes for comparing two binomial distributions
Biometrics
(1978)
E Christensen
Multivariate survival analysis using Cox's regression model
Hepatology
(1987)
AK Burroughs et al.
Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis
N Engl J Med
(1983)
D Lebrec et al.
A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a final report
Hepatology
(1984)

AM Queuniet et al.

Etude contrôlée du propranolol dans la prévention des récidives hémorragiques chez les patients cirrhotiques

Gastroentérol Clin Biol

(1987)

JP Villeneuve et al.

Propranolol for the prevention of recurrent variceal hemorrhage: a controlled trial

Hepatology

(1986)

D Westaby et al.

Improved survival following injection sclerotherapy for esophageal varices: final analysis of a controlled trial

Hepatology

(1985)

WE Fleig et al.

Prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage: prospective, randomized comparison of propranolol and sclerotherapy

Hepatology

(1987)

JM Dollet et al.

Sclérothérapie endoscopique contre propranolol après hémorragie par rupture de varices oesophagiennes chez le cirrhotique. Résultats à 4 ans d'une étude randomisée

Gastroentérol Clin Biol

(1988)

Cited by (69)

Comparison of Therapies for Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhosis: A Network Meta-analysis of Randomized Controlled Trials
2020, Clinical Therapeutics
The decision regarding the optimal secondary prophylactic treatment for esophageal variceal bleeding (EVB) in hepatic cirrhosis is controversial. A network meta-analysis was conducted to assess the benefits of various treatments for the secondary prophylaxis of EVB in patients with cirrhosis.
A thorough examination of databases, including EMBASE, PubMed, and Cochrane Database of Controlled Trials, was conducted to identify relevant randomized controlled trials up to December 2019. Key primary outcomes included mortality and rebleeding. Within the identified databases, a network meta-analysis was performed. Results were expressed by using a 95% credible interval (CrI) and odds ratios (ORs). The quality of results was assessed by using the Grading of Recommendations, Assessment, Development and Evaluation approach.
Forty-eight trials with 4415 participants with cirrhosis and portal hypertension who had a history of recent variceal bleeding were included. Carvedilol ranked first (surface under the cumulative ranking curve [SUCRA], 87.4%) in overall survival, and some advantage was suggested; however, the findings were not statistically significant, compared with endoscopic variceal ligation + nonselective beta-blockers (NSBB) (OR, 0.59; CrI, 0.28, 1.3), NSBB + isosorbide mononitrate (OR, 0.67; CrI, 0.33, 1.4), and transjugular intrahepatic portosystemic shunt (TIPS) (OR, 0.52; CrI, 0.24, 1.1). NSBB + isosorbide mononitrate (SUCRA, 63.9%) ranked higher than NSBB + endoscopic variceal ligation (SUCRA, 49.6%) in reducing mortality. TIPS (SUCRA, 98.8%) ranked higher than other treatments in reducing rebleeding but did not confer any survival benefit.
TIPS ranks first in preventing rebleeding of secondary prophylaxis of EVB and carvedilol shows outstanding efficacy in improving survival. International Prospective Register of Systematic Reviews: identifier CRD42019131814.
Pharmacotherapy plus endoscopic intervention is more effective than pharmacotherapy or endoscopy alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized, controlled trials
2009, Gastrointestinal Endoscopy
Citation Excerpt :
Romero et al38 assessed the RR by comparing the combination of sclerotherapy ligation to pharmacotherapy. All-cause mortality was lower with endoscopy in 6 studies13-18 and with pharmacotherapy in 4 studies,18,31,32,34 but the risk reduction was not statistically significant with the pooled RR ratio of 0.997 (95% CI, 0.827-1.202; P = .98). Although the risk of death caused by bleeding was lower with endoscopy in 5 studies,11,14,15,19,38 only 1 study14 found a statistically significant risk reduction (P = .035) of death caused by bleeding.
Previous clinical trials on the treatment of esophageal variceal bleeding yielded mixed results regarding the efficacy of endoscopic procedures compared with pharmacotherapy only.
To compare the efficacy of endoscopic procedures with that of pharmacotherapy in the prevention of mortality and rebleeding.
A systematic literature review was performed to identify randomized, controlled trials of the efficacy of pharmacotherapy and endoscopic therapy. A meta-analysis was performed by using the Comprehensive MetaAnalysis software package. A 2-sided α error <.05 was considered statistically significant (P < .05).
Twenty-five clinical trials with a total of 2159 patients were eligible for meta-analysis.
Relative risk (RR) with 95% confidence interval (CI) was computed for all-cause mortality, mortality from rebleeding, all-cause rebleeding, and rebleeding caused by varices.
Pharmacotherapy was as effective as endoscopic procedures in preventing rebleeding (RR 1.067; 95% CI, 0.865-1.316; P = .546), variceal rebleeding (RR 1.143; 95% CI, 0.791-1.651; P = .476), all-cause mortality (RR 0.997; 95% CI, 0.827-1.202, P = .978), and mortality from rebleeding (RR 1.171; 95% CI, 0.816-1.679; P = .39). Pharmacotherapy combined with endoscopic procedures did not reduce all-cause mortality (RR 0.787; 95% CI, 0.587-1.054; P = .108) or mortality caused by rebleeding (RR 0.786; 95% CI, 0.445-1.387; P = .405) compared with endoscopic procedures. However, combination therapy (endoscopic procedure plus pharmacotherapy) significantly reduced the incidence of all rebleeding (RR 0.623; 95% CI, 0.523-0.741; P < .001) and variceal rebleeding (RR 0.601; 95% CI, 0.440-0.820; P < .001).
Heterogeneity of patient population and different treatment protocols may have affected our meta-analysis.
Pharmacotherapy may be as effective as endoscopic therapy in reducing rebleeding rates and all-cause mortality. Pharmacotherapy plus endoscopic intervention is more effective than endoscopic intervention alone.
Acute variceal bleeding: Pharmacological treatment and primary/secondary prophylaxis
2008, Best Practice and Research: Clinical Gastroenterology
Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.
Injection therapies for variceal bleeding disorders of the GI tract
2008, Gastrointestinal Endoscopy
Variceal Hemorrhage
2006, Therapy of Digestive Disorders
Variceal hemorrhage
2005, Therapy of Digestive Disorders, Second Edition

View all citing articles on Scopus

View full text

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

Abstract

Gastroenterology

Lancet

J Hepatol

Gastroenterology

Gastrointest Endosc

Transection of the oesophagus for bleeding oesophageal varices

Br J Surg

An improved approximate formula for calculating sample sizes for comparing two binomial distributions

Biometrics

Multivariate survival analysis using Cox's regression model

Hepatology

Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis

N Engl J Med

A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a final report

Hepatology

Etude contrôlée du propranolol dans la prévention des récidives hémorragiques chez les patients cirrhotiques

Gastroentérol Clin Biol

Propranolol for the prevention of recurrent variceal hemorrhage: a controlled trial

Hepatology

Improved survival following injection sclerotherapy for esophageal varices: final analysis of a controlled trial

Hepatology

Prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage: prospective, randomized comparison of propranolol and sclerotherapy

Hepatology

Sclérothérapie endoscopique contre propranolol après hémorragie par rupture de varices oesophagiennes chez le cirrhotique. Résultats à 4 ans d'une étude randomisée

Gastroentérol Clin Biol

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