Controlled Trial of Propranolol for the Prevention of Recurrent Variceal Hemorrhage in Patients with Cirrhosis

Burroughs, Andrew K.; Jenkins, W. J.; Sherlock, Sheila; Dunk, Arthur A.; Walt, R P; Osuafor, T. O. K.; Mackie, Steven C.; Dick, Robert

doi:10.1056/nejm198312223092502

Cited by 295 publications

(62 citation statements)

References 12 publications

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“…Similar facts have been observed in the initial trials comparing PR to placebo. 22,23 From the coefficients of Cox' s regression analysis one can also estimate that risks of rebleeding or death were lower in patients older than 50 years old. The influence of age is usually not mentioned in trials assessing the treatment of portal hypertension.…”

Section: Discussionmentioning

confidence: 99%

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding

et al. 2000

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The aim of this study was to test the effectiveness of isosorbide-5-mononitrate (IM) as an adjunct to propranolol (PR) in the prevention of variceal rebleeding. Ninety-five cirrhotic patients with variceal bleeding were randomly assigned to treatment with PR ؉ IM (46 patients) or PR alone (49 patients). Eighteen patients in the PR ؉ IM group and 28 in the PR group had rebleeding during the 2 years after randomization. The actuarial probability of rebleeding 2 years after randomization was lower in the PR ؉ IM group (40.4% vs. 57.4%) but the difference was not significant (P ‫؍‬ .09). However, the decrease in the risk of rebleeding reached statistical significance after stratification according to age, i.e. less than 50 versus H50 years old, (P ‫؍‬ After the initial control of a hemorrhage due to rupture of gastric or esophageal varices, patients are at high risk of experiencing further bleeding and death. 1-3 Therapy to prevent rebleeding from esophageal varices in patients with cirrhosis is essential. Propranolol (PR), a nonselective betaadrenergic blocker, is widely used for this purpose. PR decreases portal pressure. This portal-hypotensive effect is mediated by a reduction of blood inflow into the portocollateral circulation. 4,5 Meta-analyses of data from controlled trials have confirmed that rates of rebleeding are decreased by approximately 40% and overall survival is improved by approximately 20% by PR. 6,7 However, on the basis of the hemodynamic response observed in patients, 2 problems related to PR administration still persist: first, the existence of a group of nonresponders, regardless of the administered dose; and second, the variable reduction of portal pressure seen in responders. 8,9 One possible reason for inefficacy of beta-blockers is a concomitant increase in portocollateral resistance that counteracts the hypotensive effects of decreasing blood flow through the portocollateral circulation. 10

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Section: Discussionmentioning

confidence: 99%

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding

et al. 2000

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“…Various therapeutic approaches have been tried to control acute and recurrent bleeding. The use of propranolol is of questionable long-term benefit (2)(3)(4)(5). Endoscopic sclerotherapy helps to control acute variceal hemorrhage (4, 6-8), but does not prevent subsequent bleeding (9).…”

Section: Introductionmentioning

confidence: 99%

Hepatic and renal metabolism before and after portasystemic shunts in patients with cirrhosis.

Owen¹,

Mozzoli²,

Reichle³

et al. 1985

J. Clin. Invest.

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Hepatic cirrhosis with portal hypertension and gastroesophageal hemorrhage is a disease complex that continues to be treated by surgical portasystemic shunts. Whether or not a reduction or diversion of portal blood flow to the liver adversely affects the ability of the liver to maintain fuel homeostasis via gluconeogenesis, glycogenolysis, and ketogenesis is unknown.11 patients with biopsy-proven severe hepatic cirrhosis were studied before and after distal splenorenal or mesocaval shunts. Hepatic, portal, and renal blood flow rates and glucose, lactate, pyruvate, glycerol, amino acids, ketone bodies, free fatty acids, and triglyceride arteriovenous concentration differences were determined to calculate net precursor-product exchange rates across the liver, gut, and kidney. The study showed that hepatic contribution of glucose and ketone bodies and the caloric equivalents of these fuels delivered to the blood was not adversely affected by either a distal splenorenal or mesocaval shunt. In addition to these general observations, isolated findings emerged. Mesocaval shunts reversed portal venous blood and functionally converted this venous avenue into hepatic venous blood. The ability of the kidney to make a substantial net contribution of ketone bodies to the blood was also observed.

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“…Most clinical experience in cirrhotic patients with portal hypertension has been obtained with the nonselective beta-blocker propranolol. Lebrec's [41,43] report of a significant decrease of gastrointestinal rebleeding events after continuous oral administration of propranolol was not confirmed by Burroughs et al [9]. Explanations for these discrepant results might be differences in etiology or severity of cirrhosis, selection or randomization bias or possibly a reduced hemodynamic response to propranolol due to down regulation of beta-adrenoceptors in decompensated cirrhotics who were included in the British, but not in the French study [11,26,50].…”

Section: Beta-blockers For Prophylaxis Of First Variceal Hemorrhagementioning

confidence: 88%

Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis

et al. 1986

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Summary. Prophylaxis of bleeding from esophageal varices is a very tempting concept at first glance, especially under the assumption of a high mortality associated with first variceal hemorrhage. Up to now four different measures have been tried for prophylaxis: portacaval shunt operation, devascularization procedures, sclerotherapy, and drugs. With the exception of portacaval shunts, ongoing controlled trials show a weak trend toward reduction of variceal bleeding and prolongation of survival in selected patients with compensated cirrhosis and large varices. However, prophylaxis of first variceal bleeding must still be regarded as experimental and should be restricted to controlled clinical studies.

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Controlled Trial of Propranolol for the Prevention of Recurrent Variceal Hemorrhage in Patients with Cirrhosis

Cited by 295 publications

References 12 publications

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding

Hepatic and renal metabolism before and after portasystemic shunts in patients with cirrhosis.

Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis

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