Beta‐blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation

Summary Background The safety of non‐selective β‐blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined. Aim To evaluate potential limits of the therapeutic window of non‐selective β‐blocker therapy in patients with cirrhosis and ascites Methods The impact of non‐selective β‐blockers on 28‐day transplant‐free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute‐on‐chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg. Results Treatment with non‐selective β‐blockers was associated with a higher 28‐day transplant‐free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute‐on‐chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non‐selective β‐blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non‐selective β‐blocker intake was consistently associated with superior transplant‐free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute‐on‐chronic liver failure (hazard ratio: 0.480 P = .034). Conclusions Ascites, acute‐on‐chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non‐selective β‐blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non‐selective β‐blocker treatment.

Section: Discussionsupporting

confidence: 85%

Systemic arterial blood pressure determines the therapeutic window of non‐selective beta blockers in decompensated cirrhosis

Tergast

Kimmann

Laser

et al. 2019

“…This describes the impact that severe ascites has on the day-to-day life of patients and also emphasises the unmet need for new therapies in this patient group. [28][29][30] Compared with repeated large volume paracentesis, HRQL in this group of patients was shown to be improved with interventions to control ascites, such as alfapump insertion [31][32][33] and transjugular intrahepatic portosystemic shunt (TIPSS) insertion. [34][35][36] Given the relatively low Our study showed that the quality of life of patients without oedema is marginally better, regardless of the severity of oedema.…”

Section: Discussionmentioning

confidence: 98%

Quality of life measures predict mortality in patients with cirrhosis and severe ascites

Macdonald

Jepsen

Alrubaiy

et al. 2018

Summary Background Severe ascites is associated with both a poor health‐related quality of life (HRQL) and a mortality in excess of that captured by current prognostic clinical scores. Aim To determine the association between HRQL and mortality in patients with severe ascites. Methods The HRQL data from previously published randomised controlled trials examining the efficacy of satavaptan in ascites were retrospectively evaluated. Results Of the 496 patients randomised who completed the SF‐36, 405 patients had complete datasets and were included in the analysis (difficult‐to‐treat ascites, n = 164 or refractory ascites, n = 241). Overall, patients reported poor HRQL, in particular the physical component score (PCS) of SF‐36. The physical component score (PCS) correlated with the mental component score (MCS) of SF‐36 (Spearman rank correlation = 0.68) but not with markers of severity of liver disease. The PCS, but not the MCS, was significantly lower in patients who died (P = 0.01 and P = 0.84, respectively). After confounder‐adjustment, the hazard ratio for a 10‐point increase in the physical component score was 0.83 (95% CI; 0.72‐0.97) for all‐cause mortality and 0.84 (95% CI; 0.71‐0.99) for cirrhosis‐related deaths only, indicating that patients with better physical HRQL live longer on average. Conclusions Poor physical component score (PCS) of SF‐36 is an independent predictor of 12‐month mortality in patients with severe ascites independent of current prognostic clinical scores. It holds promise not only in prognostic modelling but also as an endpoint in the evaluation of therapies targeting ascites.

“…Similar to previous studies, we found that higher Child‐Pugh score and the presence of severe/refractory ascites had a significant impact on rebleeding and mortality. Given the recent debate on the safety of NSBB therapy in patients with refractory ascites we assessed the effects of NSBB therapy in subgroups with compensated and decompensated cirrhosis separately. Interestingly, the considerable reduction of 6‐month mortality with NSBB + EBL combination vs EBL monotherapy was most pronounced in patients without severe/refractory ascites (HR: 0.37, P = 0.001), while in patients with severe/refractory ascites, NSBB addition to EBL did not have an independent beneficial effect on survival within the first 6 months (HR: 0.80, P = 0.567).…”

Section: Discussionmentioning

confidence: 98%

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding

Pfisterer

Dexheimer

Fuchs

et al. 2018

Summary Background Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non‐selective beta‐blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. Aim To assess (re‐)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. Methods (Re‐)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. Results Seven hundred and sixty‐six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log‐rank: P = 0.353) nor mortality (log‐rank: P = 0.497) as compared to EBL alone. In SP, similar re‐bleeding rates were documented in EBL + NSBB vs EBL alone (log‐rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log‐rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6‐months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). Conclusions EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.