Beta-Adrenergic–Antagonist Drugs in the Prevention of Gastrointestinal Bleeding in Patients with Cirrhosis and Esophageal Varices

Poynard, Thierry; Calès, Paul; Pasta, Linda; Idéo, G.; Pascal, Jean‐Pierre; Pagliaro, Luigi; Lebrec, Didier

doi:10.1056/nejm199105303242202

Cited by 451 publications

(97 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…That this subgroup contributes to increased mortality in the former propranolol group is consistent with conclusions from a combined analysis of 589 patients, which showd a statistically significant reduction in EVH-related mortality resulting from ␤ blockers. 22 Increased mortality in the former propranolol group, if it is related to propranolol withdrawal, indirectly strengthens the argument that propranolol administration improves mortality compared with placebo in patients with gastroesophageal varices, a conclusion that few studies have been able to determine prospectively, likely secondary to type II error.…”

Section: Discussionmentioning

confidence: 82%

Propranolol for the prevention of first esophageal variceal hemorrhage: A lifetime commitment?

Abraczinskas

2001

Hepatology

117

View full text Add to dashboard Cite

Although ␤ blockers have had significant impact in the treatment of portal hypertension, the question of how long they should be continued for prevention of variceal hemorrhage remains unknown. Prospective studies on ␤ blockers to prevent variceal hemorrhage lack long-term follow-up, and indefinite administration of ␤ blockers for primary prevention of variceal bleeding has become standard practice. The aim of this study was to determine the outcomes of patients in whom ␤ blocker therapy was discontinued. Patients completing a prospective, randomized, double-blind, placebo-controlled trial of propranolol for the primary prevention of variceal hemorrhage were tapered off of propranolol and placebo and followed prospectively for subsequent events. Of the 49 patients in the follow-up study (25 former propranolol, 24 former placebo), 9 experienced variceal hemorrhage (6 former propranolol, 3 former placebo). Following withdrawal of propranolol, the freedom from variceal bleeding was not significantly different between these 2 groups of patients, suggesting that the protective effect of propranolol against variceal hemorrhage, noted previously, was no longer present. Seventeen patients died (12 former propranolol, 5 former placebo) during the follow-up study. Cumulative survival was longer in the placebo group. These trends for EVH and survival were opposite to those observed in the original study population while patients were taking medication. When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population. Patients who discontinue ␤ blockers experience increased mortality compared with an untreated population. These observations support the current practice of indefinite prophylactic therapy. (HEPATOLOGY 2001;34:1096-1102.)

show abstract

Section: Discussionmentioning

confidence: 82%

Propranolol for the prevention of first esophageal variceal hemorrhage: A lifetime commitment?

Abraczinskas

2001

Hepatology

117

View full text Add to dashboard Cite

show abstract

“…1 Recently, it was also shown that the efficacy of beta-blockers may be enhanced by the addition of long-acting nitrates. 2 These treatments, however, do not abolish the risk of bleeding but decrease it by half or by three quarters, respectively.…”

mentioning

confidence: 99%

The Hemodynamic Response to Medical Treatment of Portal Hypertension As A Predictor of Clinical Effectiveness in the Primary Prophylaxis of Variceal Bleeding in Cirrhosis

et al. 2000

View full text Add to dashboard Cite

In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by >20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta-blockers or beta-blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was <12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow-up was significantly higher in poor responders (41%) than in good responders (7%; P ‫؍‬ .0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow-up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (␤ ‫؍‬ 1.91; SE(␤) ‫؍‬ 0.80; P ‫؍‬ .01). During follow-up 11 patients died of hepatic causes. Survival was related to Child-Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta-blockers or beta-blockers plus nitrates. (HEPATOLOGY 2000;32:930-934.)It is clearly established that prophylaxis with beta-blockers decreases the risk of first variceal bleeding in cirrhotic patients with portal hypertension and esophageal varices at risk of bleeding. 1 Recently, it was also shown that the efficacy of beta-blockers may be enhanced by the addition of long-acting nitrates. 2 These treatments, however, do not abolish the risk of bleeding but decrease it by half or by three quarters, respectively. For these reasons, it may be useful to know factors predicting clinical response or nonresponse to treatment to allow treatment of nonresponders with alternative methodologies.In patients treated with beta-blockers 3-5 or beta-blockers plus nitrates 6 for prevention of rebleeding, it was observed that a decrease in portal pressure under chronic treatment, expressed as a decrease in hepatic venous pressure gradient (HVPG), is a strong predictor of clinical effectiveness. Indeed, decreases of HVPG to 12 mm Hg or less, or decreases by at least 20% from baseline values were associated with a negligible risk of rebleeding, whereas risk of rebleeding was confined to patients not meeting these hemodynamic end points. A single report was unable to confirm the clinical value of these hemodynamic end points. 7 In the clinical setting of prophylaxi...

show abstract

“…Propranolol ca. 80-120 mg/Tag als Dauertherapie) (23). Bei Propranolol-Unverträglichkeit kann heute die endoskopische Ligatur bereits als Zweitlinientherapie zur Primärpro-phylaxe empfohlen werden (14), jedoch nicht die endoskopische Sklerosierungstherapie oder Shuntverfahren.…”

Section: Primäre Blutungsprophylaxeunclassified

Liver cirrhosis - Complications and treatment

Schepke

Reichel²,

Ziske³

et al. 2001

Dtsch med Wochenschr

View full text Add to dashboard Cite

Die Behandlung der Leberzirrhose zielt darauf, das Fortschreiten der Erkrankung zu verhindern, Komplikationen zu behandeln, eine vollwertige Ernährung sicherzustellen sowie eine Lebertransplantation rechtzeitig zu evaluieren. Letztere sollte -gerade in Anbetracht der langen Wartezeiten in Deutschland -frühzeitig erwogen werden, und zwar immer dann, wenn die Überlebenswahrscheinlichkeit des Patienten für das kommende Jahr unter 80% liegt. Hier helfen statistische Prognose-Modelle. Bei kompensierter Zirrhose (Child-Pugh A) steht die Verhinderung des Fortschreitens zur Dekompensation und zu Komplikationen im Vordergrund (antivirale Therapie mit α-Interferon oder Nukleosidanaloga bei chronischer Virushepatitis, Alkoholkarenz bei äthylischer Zirrhose, Aderlass bei der Hämochromatose, Beeinflussung der Kupferaufnahme und -ausscheidung bei M. Wilson, Immunsuppression bei der autoimmunen Hepatitis, Behandlung mit Ursodesoxycholsäure bei der primär biliären Zirrhose, Verhinderung der ersten Varizenblutung durch Propranolol). Gelingt dies, so haben die Patienten eine Lebenserwartung von vielen Jahren. Gelingt dies nicht, so münden chronische Lebererkrankungen ganz unterschiedlicher Ätiologien in ähnliche Krankheitsverläufe der Dekompensation. Gastrointestinale Blutung bei LeberzirrhoseDie häufigsten gastrointestinalen Blutungsquellen bei Leberzirrhose sind Ösophagus-und Magenfundusvarizen. Bei etwa 30% aller Patienten mit Leberzirrhose ist eine obere gastrointestinale Blutung, meist aus Ösophagusvarizen, die primäre Todesursache. Neben der Notfallbehandlung der akuten Varizenblutung werden die primäre Blutungsprophylaxe und die Rezidivblutungsprophylaxe unterschieden.

show abstract

Beta-Adrenergic–Antagonist Drugs in the Prevention of Gastrointestinal Bleeding in Patients with Cirrhosis and Esophageal Varices

Abstract: Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.

Cited by 451 publications

References 11 publications

Propranolol for the prevention of first esophageal variceal hemorrhage: A lifetime commitment?

Propranolol for the prevention of first esophageal variceal hemorrhage: A lifetime commitment?

The Hemodynamic Response to Medical Treatment of Portal Hypertension As A Predictor of Clinical Effectiveness in the Primary Prophylaxis of Variceal Bleeding in Cirrhosis

Liver cirrhosis - Complications and treatment

Contact Info

Product

Resources

About