Ligation or Propranolol for Esophageal Varices?
Jeffrey T. Kirchner
Esophageal varices often spontaneously bleed; this condition is associated with mortality rates of 30 to 70 percent. Consequently, various therapies have been used to treat patients with bleeding from hepatic cirrhosis and large esophageal varices. The most effective medical therapy is use of a nonselective beta blocker, which has been shown to reduce the incidence of first bleeding episodes and bleeding-related mortality. However, side effects often limit the use of these drugs. More aggressive therapies include endoscopic sclerotherapy and variceal ligation. Because of conflicting results in some studies, sclerotherapy is no longer recommended. Sarin and colleagues performed a prospective randomized trial that compared the safety and efficacy of endoscopic ligation and propranolol therapy in the primary prevention of variceal bleeding.
Eligible patients included those with portal hypertension and grade 3 (3 to 6 mm) or grade 4 (greater than 6 mm) varices diagnosed by endoscopy. None of the patients had a prior history of variceal bleeding. After application of exclusion criteria, patients were randomly assigned at the time of the first endoscopic examination to undergo ligation or receive propranolol. Baseline electrocardiography and cardiac evaluation were performed after 15 minutes of rest. Propranolol was administered in a dose of 40 mg, with monitoring of the heart rate and blood pressure 12 hours and 24 hours after dosing. The dosage of the beta blocker was increased in increments of 20 to 40 mg per day until a 25 percent decrease in baseline heart rate was attained. Treatment was stopped if the heart rate dropped below 55 beats per minute or if the systolic blood pressure was less than 80 mm Hg. Patients assigned to the ligation group underwent ligation at the first endoscopy session or within 24 hours, with as many bands as possible placed in the distal 5 to 7 cm of all variceal columns (vertical veins). Endoscopic ligation was performed weekly until varices were obliterated or reduced to grade 1 size. After ligation was complete, patients underwent endoscopy monthly for three months, then once every three months until the 18-month end point. Any varices that recurred and became grade 2 or more were treated with repeat ligation.
The principle end point of the study, bleeding from the varices, was diagnosed by endoscopy. Serious bleeding was considered to be a volume greater than 1,500 mL, hemorrhage resulting in a heart rate greater than 100 beats per minute, a systolic blood pressure less than 100 mm Hg and the patient’s requiring more than 4 units of blood in six hours.
Ninety patients were enrolled in the study, with 46 assigned to receive ligation and 44 to propranolol therapy. The mean dose of propranolol was 70 mg per day. In patients receiving ligation, the mean number of endoscopy sessions was 3.2, which were performed over an average of 4.1 weeks. During the study period, four patients in the ligation group and 12 patients in the medication group experienced variceal bleeding. In three of the four patients from the ligation group, the bleeding occurred within the first six weeks, before all of the varices could be eradicated. After 18 months of follow-up, the cumulative risk of bleeding was 43 percent in the propanolol group and 15 percent in the ligation group. Each group had five deaths, all related to liver disorders. The number of deaths related to bleeding was similar between the two groups: three patients in the ligation group and four patients in the propranolol group. No serious complications occurred in the ligation group and, although 16 patients receiving a beta blocker experienced adverse effects, only two patients stopped this therapy.
The authors conclude that in patients with significant grade 3 or grade 4 esophageal varices, rubber band ligation is superior to propranolol therapy in preventing primary bleeding. They suggest further study to evaluate the combination of these two therapies in hopes of achieving even better results.
Sarin SK, et al. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med April 1, 1999;340:988-93.
COPYRIGHT 1999 American Academy of Family Physicians
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