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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Impact of an acute hemodynamic response-guided protocol for primary prophylaxis of variceal bleeding
José Ignacio Fortea, Ángela Puente, Patricia Ruiz, Iranzu Ezcurra, Javier Vaquero, Antonio Cuadrado, María Teresa Arias-Loste, Joaquín Cabezas, Susana Llerena, Paula Iruzubieta, Carlos Rodríguez-Lope, Patricia Huelin, Fernando Casafont, Emilio Fábrega, Javier Crespo
José Ignacio Fortea, Ángela Puente, Patricia Ruiz, Iranzu Ezcurra, Antonio Cuadrado, María Teresa Arias-Loste, Joaquín Cabezas, Susana Llerena, Paula Iruzubieta, Carlos Rodríguez-Lope, Patricia Huelin, Fernando Casafont, Emilio Fábrega, Javier Crespo, Servicio de Aparato Digestivo, Hospital Universitario Marqués de Valdecilla, Santander 39008, Cantabria, Spain
José Ignacio Fortea, Ángela Puente, Antonio Cuadrado, María Teresa Arias-Loste, Joaquín Cabezas, Susana Llerena, Paula Iruzubieta, Carlos Rodríguez-Lope, Patricia Huelin, Fernando Casafont, Emilio Fábrega, Javier Crespo, Instituto de Investigación Sanitaria Marqués de Valdecilla, Santander 39011, Cantabria, Spain
José Ignacio Fortea, Ángela Puente, Javier Vaquero, Antonio Cuadrado, María Teresa Arias-Loste, Joaquín Cabezas, Susana Llerena, Paula Iruzubieta, Carlos Rodríguez-Lope, Patricia Huelin, Fernando Casafont, Emilio Fábrega, Javier Crespo, Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas, Madrid 28029, Madrid, Spain
Javier Vaquero, Laboratorio de Investigación en Hepatología y Gastroenterología, Hospital General Universitario Gregorio Marañón-Instituto de Investigación Sanitaria Gregorio Marañón, Madrid 28007, Madrid, Spain
Author contributions: Fortea JI, Puente A and Crespo J designed the research; Fortea JI, Puente A, Ruiz P, Ezcurra I, Cuadrado A, Arias-Loste MT, Cabezas J, Llerena S, Iruzubieta P, Rodríguez-Lope C, Huelin P, Casafont F, and Fábrega E performed the research; Fortea JI analyzed the data; Fortea JI and Vaquero J wrote the paper; Fortea JI, Puente A, Crespo J, Vaquero J, Cuadrado A, Fábrega E and Casafont F critically revised the manuscript for important intellectual content.
Supported by Instituto de Investigación Sanitaria Marqués de Valdecilla, No. NVAL17/07 (to Fortea JI); Instituto Carlos III, No. PI15/01083 (to Vaquero J).
Institutional review board statement: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki (6th revision, 2008) as reflected in a priori approval by the Clinical Research Ethics Committee of Cantabria.
Informed consent statement: A waiver of informed consent was provided since the study was considered a retrospective review both by the Clinical Research Ethics Committee of Cantabria and the Spanish Agency of Medicines and Health Products (AEMPS).
Conflict-of-interest statement: Crespo J reports grant support and/or consultancy and lecture fees from AbbVie, Gilead Sciences, Bristol-Myers Squibb, Janssen, and MSD. The remaining authors declare no conflicts of interest.
Open-Access: This is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: José Ignacio Fortea, MD, PhD, Attending Doctor, Research Scientist, Servicio de Aparato Digestivo, Hospital Universitario Marques de Valdecilla, Av. Valdecilla s/n, Santander 39008, Cantabria, Spain. jifortea@gmail.com
Telephone: +34-94-2202520 Fax: +34-94-2202520
Received: July 23, 2018
Peer-review started: July 23, 2018
First decision: August 25, 2018
Revised: September 3, 2018
Accepted: October 9, 2018
Article in press: October 9, 2018
Published online: November 6, 2018
AIM
To evaluate the long-term outcome of an acute hemodynamic response-guided protocol in which acute responders to intravenous propranolol received traditional nonselective beta-blockers (NSBBs) and acute nonresponders received carvedilol.
METHODS
Retrospective review of a protocol for primary prophylaxis of variceal bleeding guided by the acute hemodynamic response to intravenous propranolol. Fifty-two acute responders treated with traditional NSBB (i.e. propranolol or nadolol) were compared with 24 acute nonresponders receiving carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. The primary endpoint was development of first or further decompensation. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic response.
RESULTS
Acute responders and acute nonresponders presented similar 1, 2, and 3-year probabilities of first decompensation (NSBB: 0%, 13.7%, 26.1% vs carvedilol: 0%, 20%, 20%, P = 0.968) or further decompensation (21.2%, 26.1%, 40.9% vs 21.2%, 50.0%, 50.0%, P = 0.525). A previous episode of hepatic encephalopathy was the only independent predictor of decompensation [hazard ratio (95% confidence interval): 8.03 (2.76-23.37)]. Mortality rates were similar in acute responders and acute nonresponders with compensated (P = 0.428) or decompensated cirrhosis (P = 0.429). No clinical, laboratory, endoscopic or hemodynamic parameter predicted the acute hemodynamic response. In patients receiving traditional NSBB, the acute and chronic changes of hepatic venous pressure gradient were correlated (r = 0.59, P = 0.001). Up to 69.2% of acute nonresponders gained chronic response with carvedilol.
CONCLUSION
Early identification and treatment with carvedilol of acute nonresponders to intravenous propranolol improves the clinical outcome of this high-risk group of patients, probably due to its greater effects for reducing portal pressure.
Core tip: In patients with cirrhosis treated with traditional nonselective beta-blockers (NSBBs) (i.e. propranolol and nadolol), the lack of acute hemodynamic response to intravenous propranolol has been consistently associated with a higher risk of decompensation and death. Moreover, carvedilol is more effective than traditional NSBB in reducing portal pressure. In the present study, we evaluated for the first time the clinical impact of an acute hemodynamic response-guided protocol for the primary prophylaxis of variceal bleeding in which acute hemodynamic responders were treated with traditional NSBB and acute nonresponders with carvedilol. Importantly, the risk of decompensation and survival were similar in both groups, strongly suggesting that carvedilol improved the long-term outcome of acute nonresponders.
