Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Propranolol decreased recurrent hemorrhage from portal hypertension gastropathy in liver cirrhosis

ACP J Club. 1991 Nov-Dec;115:72. doi:10.7326/ACPJC-1991-115-3-072


Source Citation

Pérez-Ayuso RM, Piqué JM, Bosch J, et al. Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis. Lancet. 1991 Jun 15;337:1431-4. [PubMed ID: 1675316]


Abstract

Objective

To assess the effectiveness of propranolol in preventing recurrence of bleeding from severe portal hypertensive gastropathy in patients with liver cirrhosis.

Design

Randomized controlled trial.

Setting

5 hospitals in Spain.

Patients

95 patients with liver cirrhosis met the inclusion criteria of acute upper gastrointestinal bleeding or of chronic anemia with occult blood loss in ≥ 3 samples and multiple gastric red spots on endoscopy either actively bleeding or without other possible sources of bleeding. 38 patients with hepatoma, contraindications to propranolol previous β-blocker therapy, massive portal hypertensive gastropathy hemorrhage, or who refused consent, were excluded.

Intervention

Patients received either propranolol, twice daily at a dose causing the resting heart rate to fall by 25% or to < 55 beats/min (n = 26) or to no treatment other than iron when necessary (n = 28). Follow-up visits were scheduled every 2 months after hospital discharge; liver and renal function tests, checks of iron requirements, and endoscopy by a physician blinded to the treatment assignment were done every 6 months.

Main outcome measures

Recurrence of hemorrhage from portal hypertensive gastropathy, as either acute upper gastrointestinal bleeding with a fall in hematocrit of > 5 points and endoscopically proven bleeding from gastric red spots, or chronic bleeding meeting predetermined criteria.

Main results

The mean dose of propranolol was 120 mg/d (SD 74; range, 40 to 320 mg/d). Mean follow-up was 21 and 18 months for the propranolol and control groups, respectively. More patients in the propranolol group were free of recurrent bleeding after 12 months (65% vs 38%, P < 0.05) and at 30 months of follow-up, (52% vs 7%, P < 0.05). Propranolol reduced recurrent bleeding independently of the initial acuteness of bleeding. More patients were free of acute bleeding in the propranolol group after 12 months (91% vs 70%, P < 0.05) and at 30 months of follow-up (85% vs 20%, P < 0.05), but there was no difference between the groups for chronic bleeding. Multivariate analysis showed that only absence of propranolol was predictive of recurrent bleeding. Differences in survival at 12 and 30 months favored the propranolol group, but were not significant (P = 0.14).

Conclusion

Propranolol, at an average dose of 120 mg/d, decreased the incidence of recurrent bleeding from severe portal hypertensive gastropathy in patients with liver cirrhosis.

Source of funding: Fondo de Investigacions Sanitarias de la Seguidad Social (Spain).

Address for article reprint: Dr. R.M. Pérez-Ayuso, Gastroenterology Department, Hospital Clínic i Provincial, Villaroel 170, 08036 Barcelona, Spain.


Commentary

This study confirms and extends the observations of Lebrec and colleagues in 1981 (1) that propranolol reduces the risk for recurrent bleeding from esophageal varices and gastritis in patients with cirrhosis (1). In contrast to other studies that included primarily patients with alcoholic cirrhosis, half of the patients in this study had nonalcoholic liver disease. Although most of the patients in Lebrec's trial had bled from esophageal varices, 24% had only gastritis. Propranolol was equally effective in preventing recurrent bleeding from gastritis and esophageal varices. Hence, it is not surprising that Pérez-Ayuso and colleagues found that propranolol lowered the likelihood of acute recurrent bleeding from gastric lesions. It is unclear why propranolol was less effective in preventing chronic gastrointestinal blood loss. Much has been learned since 1981 about the pathophysiology of gastritis in portal hypertension. The gastric lesion, now called portal hypertensive gastropathy, results from longstanding portal hypertension. The hyperemia noted on endoscopy is caused by dilated vessels in the mucosa (capillaries) and submucosa (veins) and not by inflammation. Patients are typically hypochlorhydric, which is why acid-lowering regimens often fail to prevent recurrence. Why some patients with portal hypertension develop primarily esophageal varices and others, hypertensive gastropathy, remains unclear. However, because both result from the same underlying problem, and because propranolol lowers portal blood flow and portal pressure, it makes sense that propranolol is effective in lessening recurrent bleeding in both disorders.

This study, therefore, provides further evidence to support the use of propranolol in patients who bleed from hypertensive gastropathy and suggests that efficacy is independent of the cause of the underlying liver disease.

Marshall M. Kaplan, MD
Tufts UniversityBoston, Massachusetts, USA


Reference

1. Lebrec D, Poynard T, Hillon P, Benhamou JP. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis. N Engl J Med. 1981;305:1371-4.