Carvedilol Improves Portal Pressure in Patients with Advanced Cirrhosis
SAN FRANCISCO, CA—Response rates among patients with advanced liver cirrhosis who were administered carvedilol to reduce portal pressure were superior to those achieved with propranolol, according to authors of the randomized, open-label, long-term CARPE study. Findings were reported at The Liver Meeting® 2015.
At a dose of 12.5mg/day, however, carvedilol was not superior to propranolol at achieving a target reduction in hepatitis venous pressure gradient (HVPG), reported lead study author Sang Gyune Kim, MD, of the Soonchunhyang University Hospital, in Bucheon Si, Korea, and coauthors.
"Propranolol has been used in the primary prophylaxis of variceal bleeding in patients with cirrhosis,” Dr. Kim explained. However, "more recent data suggest that carvedilol may be more effective in reducing HVPG than propranolol."
To evaluate and compare hemodynamic response rates of carvedilol and propranolol, 110 patients with Grade 2 or 3 esophageal varices and HVPG of ≥12mmHg at baseline were randomly assigned to receive daily carvedilol (n=55) or propranolol (n=55).
At baseline, patients in the carvedilol and propranolol groups exhibited no significant differences in age, sex, cirrhosis etiology, Child-Pugh Score class, MELD score, or average HVPG (17.2±4.1 vs. 18.0±4.9mmHg), Dr. Kim noted.
HVPG was re-measured in 6 weeks. Responders were defined as those patients whose HVPG fell ≥20% or fell to values <12mmHg, compared to baseline. “All data were analyzed by both intention-to-treat (ITT) and per-protocol (PP),” Dr. Kim noted.
The proportion of responders did not differ significantly between the carvedilol and propranolol groups (ITT analysis, 49.1% vs. 30.9%; P=0.08; PP analysis, 57.4% vs. 39.5%; P=0.137), the study found, nor did differences between the groups' average reductions in HVPG, heart rate, or blood pressure.
“However, the patients with MELD scores of ≥15 taking carvedilol had a significantly higher response rate than those taking propranolol (ITT: 58.3% vs. 0; P=0.005),” Dr. Kim reported. No responder in the propranolol group had a MELD score of ≥15. “Similarly, the presence of ascites also had a significant influence on response rate (ITT: 51.5% vs. 24.2%; P=0.042).”
The incidence of drug-associated adverse events did not differ between carvedilol and propranolol, 12.7% vs. 23.6%: P=0.152, with study medication compliance also comparable between the two groups (85.5% vs. 78.2%; P=0.322).