Non-Selective Beta-Blockers in Liver Cirrhosis: the Effect of the "Therapeutic Window" and Patient Survival

Objectives of the study: to analyze the survival rate of patients who received and did not receive various drugs of the class of non-selective beta-blockers (NSBB) while waiting for liver transplantation (LT) on the waiting list for liver transplantation (WLLT), depending on the presence or absence of a "therapeutic window" for the appointment of NSBB; to determine risk factors for death when prescribing various representatives of the NSBB class in patients with refractory ascites (RA). Material and methods. The retrospective case-control study was conducted. The "case" group included 278 adult patients with decompensated liver diseases of various etiologies included in the WLLT, who were treated with NSBB while waiting for LT. The "control" group consisted of 72 patients with decompensated liver diseases of various etiologies included in the WLLT, who did not receive NSBB therapy during the waiting period for LT. For the subsequent analysis, the group of patients receiving NSBB (n = 278) was divided into two subgroups: with the presence of a "therapeutic window" (n = 175), and without it (n = 103). The survival rate of patients was determined by the Kaplan - Mayer method. Predictors of mortality of patients receiving NSBB in the absence of a" therapeutic window "for NSBB were determined using the Cox proportional hazards model in the groups of patients with RA (n = 103) and non-RA (n = 175). Results. The survival rate of patients receiving NSBB in the presence of a" therapeutic window "for NSBB is significantly higher than in the group of patients receiving NSBB in WLLP while waiting for LT in the absence of a" therapeutic window " for NSBB (Log-Rank < 0.0001). The risk of death in patients with RA treated with NSBB was significantly higher than in patients with non-RA (HR = 2.285; CI 1.237 4.220; p = 0.008). The risk of death for patients treated with propranol was significantly different from carvedilol (HR = 2,152 and HR = 0.765; p = 0.042, respectively). Conclusion. The results of the study confirmed the hypothesis that there is a "therapeutic window" for NSBB when they are prescribed to patients with decompensated cirrhosis of the liver and included in the WLLP. The use of NSBB contributes to an increase in the mortality of patients with RA, regardless of the type of drug, in the case when the "closed therapeutic window" phase develops. In order to reduce the mortality of patients waiting for LT for several years due to acute organ deficiency, doctors who lead patients to WLLT should assess the risk and benefit of using NSBB