title: Nonselective β-blockers do not affect mortality in cirrhosis patients with ascites: Post Hoc analysis of three randomized controlled trials with 1198 patients.
abstract: The safety of nonselective β-blockers (NSBBs) in advanced cirrhosis has been questioned. We used data from three satavaptan trials to examine whether NSBBs increase mortality in cirrhosis patients with ascites. The trials were conducted in 2006-2008 and included 1198 cirrhosis patients with ascites followed for 1 year. We used Cox regression to compare all-cause mortality and cirrhosis-related mortality between patients who did and those who did not use NSBBs at randomization, controlling for age, gender, Model for End-Stage Liver Disease score, Child-Pugh score, serum sodium, previous variceal bleeding, cirrhosis etiology, and ascites severity. Moreover, we identified clinical events predicting that a patient would stop NSBB treatment. At randomization, the 559 NSBB users were more likely than the 629 nonusers to have a history of variceal bleeding but less likely to have Child-Pugh class C cirrhosis, hyponatremia, or refractory ascites. The 52-week cumulative all-cause mortality was similar in the NSBB user and nonuser groups (23.2% versus 25.3%, adjusted hazard ratio = 0.92, 95% confidence interval 0.72-1.18), and NSBBs also did not increase mortality in the subgroup of patients with refractory ascites (588 patients, adjusted hazard ratio = 1.02, 95% confidence interval 0.74-1.40) or in any other subgroup. Similarly, NSBBs did not increase cirrhosis-related mortality (adjusted hazard ratio = 1.00, 95% confidence interval 0.76-1.31). During follow-up, 29% of initial NSBB users stopped taking NSBBs, and the decision to stop NSBB treatment marked a sharp rise in mortality and coincided with hospitalization, variceal bleeding, bacterial infection, and/or development of hepatorenal syndrome.
  
  
  
  This large and detailed data set on worldwide nonprotocol use of NSBBs in cirrhosis patients with ascites shows that NSBBs did not increase mortality; the decision to stop NSBB treatment in relation to stressful events may have added to the safety. (Hepatology 2016;63:1968-1976).
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Bossen
authors.affiliation: Department of Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.affiliation: Sanofi Aventis R&D, Paris, France.
authors.forename: Hugh
authors.initials: H
authors.lastname: Watson
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Jepsen
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use; D001201:Ascites / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control; D008103:Liver Cirrhosis / Q000150:complications / Q000401:mortality; D009025:Morpholines / Q000627:therapeutic use; D013141:Spiro Compounds / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; C103281:satavaptan; D013141:Spiro Compounds