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

Abstract

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 When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population.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.)

Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis

“…Nadolol is is usually started at a dose of 40 mg once a day (QD). Because a randomized trial showed that the risk of bleeding recurs when treatment with ␤-blockers is stopped, 59 prophylactic therapy should be continued indefinitely.…”

Primary prevention of bleeding from esophageal varices in patients with liver cirrhosis

“…The efficacy of b-blockers in the prevention of bleeding or bleedingrelated mortality was the same, independently of the cause and severity of cirrhosis, ascites and size of varices. However, when propranolol is discontinued, the risk of variceal hemorrhage returns to what would be expected in an untreated population [24] . The hemodynamic response to treatment with b-blockers is considered appropriate when HVPG is decreased below 12 mmHg or by ≥ 20% of baseline values, 1-3 mo after initiation of treatment.…”

Management of variceal haemorrhage

“…Dawka powinna być tak dobrana, aby uzyskać 25-procentowe obniżenie często-ści akcji serca (nie wolniej jednak niż 55/min), przy ciśnieniu skurczowym krwi nie niższym niż 90 mm Hg [162]. Leczenie propranololem powinno trwać całe życie i każdy pacjent powinien zostać pouczony, że nagłe odstawienie leku wiąże się z ryzykiem wystąpienia krwawienia [166].…”