A new study published in the Journal of Hepatology shows that carvedilol, a non-cardioselective beta-blocker, is more effective than traditional beta-blockers in preventing complications of cirrhosis, both in compensated patients and in those with already decompensated disease. This is the first large-scale, head-to-head comparison between carvedilol and traditional non-selective beta-blockers such as propranolol and nadolol in this setting, providing strong evidence for clinical practice.
The study included 540 patients treated at six European hospitals between 2008 and 2021, with an average follow-up of three years in compensated patients and just over two and a half years in decompensated ones. Results indicated that carvedilol reduced the risk of a first decompensation by 39% in compensated patients and reduced the combined risk of new complications or death by 43% in decompensated patients. Moreover, the safety profile of carvedilol was comparable to that of the classical drugs.
This study was the result of collaboration among several Spanish groups of the Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD). These included the teams led by Drs. Juan Carlos García-Pagán (Hospital Clínic-IDIBAPS), José Luis Calleja (Hospital Puerta de Hierro), Rafael Bañares (Hospital Gregorio Marañón), Agustín Albillos (Hospital Ramón y Cajal), and the CIBER Cirrhosis Complications group at Hospital de Sant Pau, led by Dr. Germán Soriano and coordinated at the Research Institute Sant Pau (IR Sant Pau) by Drs. Edilmar Alvarado and Cándido Villanueva. Other international centers, such as the University of Vienna, also participated, further reinforcing the robustness and international relevance of the findings.
Dr. Edilmar Alvarado highlighted the importance of the results: “Decompensation marks a turning point in the course of cirrhosis, with a direct impact on patients’ quality of life and survival. Demonstrating that carvedilol provides superior protection represents a highly significant step forward for the clinical management of patients with both compensated and decompensated cirrhosis.”
Liver cirrhosis is one of the leading causes of advanced liver disease and liver-related mortality worldwide. Its progression is usually silent until decompensation occurs—that is, when complications such as ascites (fluid accumulation in the abdomen), variceal bleeding, jaundice, or hepatic encephalopathy appear. From that point onward, the prognosis worsens considerably, and the risk of mortality and the need for liver transplantation increase.
The key factor behind these complications is the development of portal hypertension, an abnormal increase in pressure within the portal vein—the main blood vessel that carries blood from the intestines to the liver—caused by greater liver stiffness and increased blood flow within the portal circulation. This rise in pressure promotes the formation of varices in the esophagus and stomach, as well as ascites and other clinical events known as cirrhosis decompensations.
To control portal hypertension, non-selective beta-blockers (NSBBs), such as propranolol and nadolol, have been used for decades. These drugs reduce splanchnic blood flow—that is, blood from the digestive system flowing to the liver through the portal vein—and lower portal pressure, helping prevent complications. Carvedilol, in addition to blocking beta receptors, has an extra vasodilatory effect on alpha-1 receptors, leading to a greater reduction in portal pressure. This superior hemodynamic effect explains the higher potency of carvedilol as a beta-blocker and translates into the better clinical protection observed in the study.
This finding has direct implications for the management of patients with cirrhosis. Carvedilol is now established as the reference treatment for preventing complications, not only in the early stages of the disease (compensated) but also in more advanced stages (decompensated). This means its use can delay disease progression, reduce the occurrence of decompensations and hospitalizations, and improve both survival and quality of life for patients.
Based on these results, carvedilol stands out as the non-cardioselective beta-blocker of choice for treating portal hypertension in patients with liver cirrhosis. Furthermore, the data support its broader inclusion in international clinical guidelines. The evidence generated by this study could help harmonize medical practice across countries and reduce inequalities in access to more effective treatments.
Spain has a long tradition in the study of portal hypertension and its complications, and this work confirms the leadership of national research groups in this field. Collaboration among reference hospitals and the Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD) has made it possible to assemble one of the largest and most representative cohorts to date. This strengthens Spain’s role as a driving force in hepatology research.
Dr. Alvarado concluded, “The magnitude of the data and the diversity of participating centers allow us to state that carvedilol is not only more effective but may also transform how we prevent cirrhosis complications in routine clinical practice.”
Fortea JI, Alvarado-Tapias E, Simbrunner B, Ezcurra I, Hernández-Gea V, Aracil C, Llop E, Puente A, Roig C, Reiberger T, García-Pagan JC, Calleja JL, Ferrero-Gregori A, Mandorfer M, Villanueva C, Crespo J. Carvedilol vs. propranolol for the prevention of decompensation and mortality in patients with compensated and decompensated cirrhosis. J Hepatol 2025;83:70–80. https://doi.org/10.1016/j.jhep.2024.12.017
