title: Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites.
abstract: Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality.
  
  
  
  A single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1st of January 2009 to 31st August 2012 was carried out. The primary outcome was all-cause and liver-specific mortality in patients receiving or not receiving carvedilol as prophylaxis against variceal bleeding.
  
  
  
  The final cohort after propensity score matching comprised 264 patients. Baseline ascites severity and UK end-stage liver disease (UKELD) score between carvedilol (n=132) and non-carvedilol (n=132) treated patient groups were comparable. Median follow-up time was 2.3years. Survival at the end of the follow-up was 24% and 2% for the carvedilol and the non-carvedilol groups respectively (log-rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (log-rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 (95% confidence interval [CI]: 0.44, 0.80; p=0.001), suggesting a 41% reduction in mortality risk. When stratified by the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 (95% CI: 0.29, 0.77; p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk.
  
  
  
  Long-term carvedilol therapy is not harmful in patients with decompensated cirrhosis and ascites.
  
  
  
  The safety of carvedilol and other non-selective beta-blocker drugs in patients with liver cirrhosis and ascites is still debated. In this study, we have shown that carvedilol therapy in these patients was associated with reduced risk of mortality, particularly in those with mild ascites. We concluded that low dose, chronic treatment with carvedilol in patients with liver cirrhosis and ascites is not detrimental.
authors.affiliation: Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom. Electronic address: rohit.sinha@nhs.net.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Khalida A
authors.initials: KA
authors.lastname: Lockman
authors.affiliation: Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Nethmee
authors.initials: N
authors.lastname: Mallawaarachchi
authors.affiliation: Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Marcus
authors.initials: M
authors.lastname: Robertson
authors.affiliation: Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: John N
authors.initials: JN
authors.lastname: Plevris
authors.affiliation: Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D001201:Ascites / Q000188:drug therapy* / Q000401:mortality; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002423:Cause of Death; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: Ascites; Carvedilol; Decompensated liver disease; Non-selective beta-blockers