Do Nonselective Beta Blockers Increase Mortality in Patients With Cirrhosis and Ascites?
Nonselective beta blockers (NSBBs) do not significantly increase the risk of death in patients with cirrhosis and ascites or refractory ascites, researchers report in the August issue of Clinical Gastroenterology and Hepatology. The findings from this meta-analysis do not support the position that NSBBs be routinely withheld from patients with ascites.
Variceal hemorrhage, the most common lethal complication of cirrhosis, is caused by portal hypertension. NSBBs can lower a patient’s risk of first and recurrent variceal bleeding, so they are among the most widely used drugs for patients with cirrhosis.
However, NSBBs do not benefit, and are even detrimental to, patients with some complications of cirrhosis. The drugs have been proposed to increase risk of paracentesis-induced circulatory dysfunction in patients with refractory ascites. Moreover, β-blockers can cause systolic dysfunction and low cardiac output, which compromise renal perfusion. Some observational studies have found the drugs to be harmful in certain patients with cirrhosis, and randomized trials have been underpowered to detect significant differences in mortality (and did not study mortality in patients with cirrhosis and ascites as a primary end point).
Chirapongsathorn et al therefore performed a meta-analysis of data of studies of NSBBs to determine whether they are more likely to harm or help patients with cirrhosis (see Table). They analyzed data from 3 randomized control trials and 8 observational studies of propranolol, carvedilol, nadolol, or metoprolol, reporting 1206 deaths among 3145 patients with ascites. Control groups received other interventions to prevent variceal bleeding.
The authors found that use of NSBBs was not associated with increased all-cause mortality (relative risk, 0.95). Similar findings were made for patients with nonrefractory ascites (relative risk, 0.96) or refractory ascites (relative risk, 0.95).
Results were similar from the randomized controlled trials and the observational studies. Use of NSBBs was not associated with increased mortality at 6, 12, 18, or 24 months.
It important to note that most studies included in this analysis were not randomized, and there was significant heterogeneity among the observational studies.
Yet when the analysis was restricted to studies at low risk of bias, and in which there was no heterogeneity, use of NSBBs was not associated with increased all-cause mortality (relative risk, 1.02). Moreover, conclusions were the same from studies with medium to high risk of bias. No single study markedly affected the summary estimate or P values for heterogeneity.
There were not sufficient data available to perform stratified analyses based on type of NSBB agent (propranolol, nadolol, and carvedilol), dose and duration of NSBB treatment, etiology of cirrhosis (alcoholic liver disease, viral hepatitis, nonalcoholic steatohepatitis), ascitic fluid total protein, spontaneous bacterial peritonitis, age, or sex.
Chirapongsathorn et al point out that patients with ascites had a poor prognosis regardless of NSBB therapy. Mortality at 6 months was 52% in patients taking NSBBs compared with 42.5% in the control groups, but this was not statistically significant. This may be because patients who were included in the study had advanced-stage cirrhosis.
The authors state that randomized clinical trials are needed to evaluate the effects of NSBB therapy on patients with cirrhosis and ascites.
This article has accompanying CME activity.