Carvedilol Reduces Esophageal Bleeding in Cirrhosis Patients

Carvedilol Reduces Esophageal Bleeding in Cirrhosis Patients
By Chris Emery, Contributing Writer, MedPage Today
Published: August 20, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
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Action Points

* Explain to interested patients that carvedilol has been shown to prevent variceal bleeding in cirrhosis patients.


* Note that the researchers urged caution interpretation of the comparison to carvedilol, due to poor adherence to variceal band ligation in the study population.

The beta-blocker carvedilol was more effective at preventing esophageal bleeding in cirrhosis patients than variceal band ligation (VBL), without increasing mortality risk, a new study found.

Cirrhosis patients who received carvedilol had lower rates of initial bleeding from abnormally dilated submucosal veins in the lower esophagus, known as varices, compared with patients who received variceal banding ligation (RH 0.41; 95% CI 0.19 to 0.96; P<0.04), according to the report published online Aug. 19 in Hepatology.

Six patients who underwent banding ligation, an endoscopic procedure in which rubber bands are looped around the dilated veins in the esophagus, bled from ulcers that resulted from the banding.

"This study is the first randomized, controlled trial to assess the role of carvedilol in the prevention of the first variceal bleed in patients with high-risk varices," Peter C. Hayes, MD, PhD, FRCP, of the Royal Infirmary of Edinburgh, and colleagues wrote. "We have found carvedilol to have lower bleeding rates than VBL, with no difference in survival."

Variceal hemorrhages are the most most serious complication of high blood pressure in the portal vein (portal hypertension), which is often related to chronic liver disease. About 5% of cirrhosis patients will suffer from esophageal varices annually, with bleeding in about a third of those cases.

Two recent reviews of 16 previous trials comparing VB and beta-blockers for primary prevention of bleeding found that VBL was more effective, although the difference in effectiveness disappeared in one meta-analysis studies when potentially biased studies were excluded.

However, none of the trials on variceal hemorrhages investigated the effectiveness of carvedilol, a noncardioselective beta-blocker with weak vasodilating properties that is sold as a generic drug and under brand names such as Coreg, Dilatrend, Eucardic and Carloc.

In this study, Hayes and colleagues sought to compare carvedilol and VBL for the prevention of the first variceal bleed in a randomized, controlled multicenter trial.

They randomly assigned 152 cirrhosis patients (median age 54) from five different medical centers to receive either 12.5 milligrams of carvedilol once daily or VBL performed every two weeks using an endoscopic banding device until the serious (worse than grade 1) varices disappeared.

Of the patients in the study, 75% suffered from alcoholic cirrhosis and all had grade II or larger esophageal varices.

After randomization, the patients were followed for a median of 20 months. Among the patients who received carvedilol, 39 experienced side effects, most of which were minor and resolved with continued use.

However, 10 patients could not tolerate persistent side effects, including shortness of breath, impotence, nausea and vomiting, and symptomatic hypotension, and they discontinued the treatment. A total of 13 patients discontinued the banding treatment as well, often because they found the procedure uncomfortable.

Variceal bleeding occurred in eight patients (10%) in the carvedilol group and 17 patients (23%) in the banding group during the follow-up period. The researchers found no difference in overall mortality or bleeding-related mortality between the two treatments.

The researchers concluded that carvedilol was effective at preventing the first variceal bleed and is well tolerated but cautioned that difficulties in adherence to the banding protocol in their study may have effected the results.

"Further studies should aim to increase compliance with VBL protocols, with particular emphasis on variceal eradication," they wrote. "However, we believe that carvedilol can be considered a treatment option for primary prophylaxis of variceal bleeding."

The study was supported by the University of Edinburgh.

The researchers reported no financial conflicts of interest.

Primary source: Hepatology
Source reference:
Hayes P, et al "Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed" Hepatology 2009; DOI: 10.1002/hep.23045.