Non-selective β-blockers do not affect mortality in cirrhosis patients with ascites: Post hoc analysis of three RCTs with 1198 patients.
Hepatology. 2015 Nov 24;
Authors: Bossen L, Krag A, Vilstrup H, Watson H, Jepsen P
The safety of non-selective 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 or did not use NSBBs at randomisation, controlling for age, gender, MELD score, Child-Pugh score, serum sodium, previous variceal bleeding, cirrhosis aetiology, and ascites severity. Moreover, we identified clinical events predicting that a patient would stop NSBB treatment. At randomisation, the 559 NSBB users were more likely than the 629 non-users 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 non-user groups (23.2% vs. 25.3%, adjusted HR=0.92, 95% CI 0.72-1.18), and NSBBs also did not increase mortality in the subgroup of patients with refractory ascites (588 patients, adjusted HR=1.02, 95% CI 0.74-1.40) or in any other subgroup. Similarly, NSBBs did not increase cirrhosis-related mortality (adjusted HR=1.00, 95% CI 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 hospitalisation, variceal bleeding, bacterial infection, and/or development of the hepatorenal syndrome.
CONCLUSION: This large and detailed dataset on worldwide non-protocol use of NSBBs in cirrhosis patients with ascites shows that NSBBs did not increase the patients' mortality. The decision to stop NSBB treatment in relation to stressful events may have added to the safety. This article is protected by copyright. All rights reserved.
PMID: 26599983 [PubMed - as supplied by publisher]