Carvedilol vs. propranolol for the prevention of decompensation and mortality in patients with compensated and decompensated cirrhosis

Abstract

Background & aims: Data on the effectiveness of classical non-selective beta-blockers (cNSBBs, i.e., propranolol and nadolol) vs. carvedilol in patients with cirrhosis are scarce. In the present study, we aimed to compare their potential for preventing decompensation and mortality in patients with compensated and decompensated cirrhosis.

Methods: We performed a multicenter retrospective study including patients with compensated and decompensated cirrhosis with clinically significant portal hypertension, undergoing measurement of hepatic venous pressure gradient (HVPG) to assess acute hemodynamic response to intravenous propranolol (i.e., HVPG decrease ≥10% from baseline value) prior to primary prophylaxis for variceal bleeding. Outcomes were adjusted using inverse probability of treatment weighting in a competitive risk framework.

Results: A total of 540 patients were included, 256 with compensated (cNSBBs n = 111; carvedilol n = 145) and 284 with decompensated (cNSBBs n = 134; carvedilol n = 150) cirrhosis. Median follow-up was 36.3 (IQR 16.9-61.0) and 30.7 (IQR 13.1-52.2) months, respectively. After covariate balancing, compared to cNSBBs, carvedilol significantly reduced the risk of a first decompensation in compensated patients (subdistribution hazard ratio 0.61; 95% CI 0.41-0.92; p = 0.019) and a combined endpoint of further decompensation/death in decompensated patients (subdistribution hazard ratio 0.57; 95% CI 0.42-0.77; p <0.0001). A second HVPG was conducted on 176 (68.8%, compensated) and 177 (62.3%, decompensated) patients. Acute non-responders, both compensated (11.1% vs. 29.4%; p = 0.422) and decompensated (16.0% vs. 43.6%: p = 0.0247) patients, showed a higher likelihood of achieving a chronic hemodynamic response with carvedilol. The safety profile of each type of NSBB was comparable in both cohorts.

Conclusions: Our data endorse the current recommendation favoring the use of carvedilol for the prevention of a first decompensation of cirrhosis and suggest extending the recommendation to patients with decompensated cirrhosis without recurrent or refractory ascites.

Impact and implications: This study addresses a gap in the comparative effectiveness of classical non-selective beta-blockers (e.g., propranolol and nadolol) vs. carvedilol in managing cirrhosis in both compensated and decompensated stages. Our results support the preferential use of carvedilol in both settings due to its superior efficacy in reducing first and further decompensation. However, owing to the retrospective nature of the study and inherent selection biases, we advise against broadly applying these findings to patients with decompensated cirrhosis who exhibit signs of circulatory dysfunction or recurrent/refractory ascites.

Keywords: Liver Cirrhosis; Nadolol; Non-selective beta-blocker; Portal hypertension.