Conversion of Propranolol to Carvedilol Improves Renal Perfusion and Outcome in Patients With Cirrhosis and Ascites.

Abstract

In recent years, concerns have been raised on the potential adverse effects of nonselective beta-blockers, and particularly carvedilol, on renal perfusion and survival in decompensated cirrhosis with ascites. We investigated the long-term impact of converting propranolol to carvedilol on systemic hemodynamics and renal function, and on the outcome of patients with stable cirrhosis and grade II/III nonrefractory ascites. Ninety-six patients treated with propranolol for esophageal varices' bleeding prophylaxis were prospectively evaluated. These patients were randomized in a 2:1 ratio to switch to carvedilol at 12.5 mg/d (CARVE group; n=64) or continue propranolol (PROPRA group; n=32). Systemic vascular resistance, vasoactive factors, glomerular filtration rate, and renal blood flow were evaluated at baseline before switching to carvedilol and after 6 and 12 months. Further decompensation and survival were evaluated at 2 years. During a 12-month follow-up, carvedilol induced an ongoing improvement of systemic vascular resistance (1372±34 vs. 1254±33 dynes/c/cm5; P=0.02) along with significant decreases in plasma renin activity (4.05±0.66 vs. 6.57±0.98 ng/mL/h; P=0.01) and serum noradrenaline (76.7±8.2 vs. 101.9±10.5 pg/mL; P=0.03) and significant improvement of glomerular filtration rate (87.3±2.7 vs. 78.7±2.3 mL/min; P=0.03) and renal blood flow (703±17 vs. 631±12 mL/min; P=0.03); no significant effects were noted in the PROPRA group. The 2-year occurrence of further decompensation was significantly lower in the CARVE group than in the PROPRA group (10.5% vs. 35.9%; P=0.003); survival at 2 years was significantly higher in the CARVE group (86% vs. 64.1%; P=0.01, respectively). Carvedilol at the dose of 12.5 mg/d should be the nonselective beta-blocker treatment of choice in patients with cirrhosis and nonrefractory ascites, as it improves renal perfusion and outcome.