Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis

Abstract

Short-term carvedilol administration is more powerful than propranolol in decreasing hepatic venous pressure gradient (HVPG) in cirrhotic patients, but induces arterial hypotension that may prevent its long-term use in portal hypertensive patients. This study compared the HVPG reduction and safety of long-term carvedilol and propranolol. Fifty-one cirrhotic patients were randomly assigned to receive carvedilol (n = 26) and propranolol (n = 25). Hemodynamic measurements and renal function were assessed at baseline and after 11.1 +/- 4.1 weeks. Carvedilol caused a greater decrease in HVPG than popranolol (-19 +/- 2% vs. -12 +/- 2%; P <.001). The proportion of patients achieving an HVPG reduction >/=20% or </=12 mm Hg was greater after carvedilol (54% vs. 23%; P <.05). Carvedilol, but not propranolol caused a significant decrease in mean arterial pressure (MAP) (-11 +/- 1% vs. -5 +/- 3%; P =.05) and a significant increase in plasma volume (PV) and body weight (11 +/- 5% and 2 +/- 1%, respectively; P <.05). Glomerular filtration rate (GFR) was unchanged with either drug, but the dose of diuretics was increased more frequently after carvedilol (27% vs. 8%; P =.07). Adverse events requiring discontinuation of treatment occurred in 2 patients receiving carvedilol and in 3 receiving propranolol. In conclusion, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis. However, its clinical applicability may be limited by its systemic hypotensive effects. Further trials are needed to confirm the therapeutic potential of carvedilol.

Hemodynamic effects of one week of carvedilol administration on cirrhotic rats

“…Similar observations of a reduction of heart rate and cardiac index have been demonstrated in cirrhotic patients receiving either acute or chronic carvedilol. [21][22][23][24] However, we found that chronic carvedilol administration did not affect mean arterial pressure in cirrhotic rats. Similarly, previous studies have shown that chronic administration of carvedilol in patients with cirrhosis causes a smaller reduction or an insignificant change in mean arterial pressure than acute administration.…”

“…20 Hemodynamic studies in patients with cirrhosis have found that carvedilol effectively decreases portal pressure without compromising hepatic blood flow or renal function. [21][22][23][24][25] A recent study reported that carvedilol has a greater portal hypotensive effect than propranolol alone in patients with cirrhosis. 23 The current study was undertaken to evaluate the possible mechanism of carvedilol on hemodynamics in cirrhotic rats with portal hypertension.…”

Maintenance of hemodynamic response to treatment for portal hypertension and influence on complications of cirrhosis

“…Nevertheless, only around half the patients reach an appropriate hemodynamic response with this treatment. It has been suggested that carvedilol [31], or the combination of propranolol and prazosin [32], may significantly increase this rate of response. However, these medications also induce a higher proportion of side effects, mainly arterial hypotension and fluid retention [31,32].…”

“…It has been suggested that carvedilol [31], or the combination of propranolol and prazosin [32], may significantly increase this rate of response. However, these medications also induce a higher proportion of side effects, mainly arterial hypotension and fluid retention [31,32]. Obviously, other pharmacological options devoid of systemic effects should be evaluated to enhance the portal hypotensive effect achieved with the medications currently available [2,33].…”

Cardiovascular Risk Assessment of the Liver Transplant Candidate

“…It has been demonstrated to cause a reduction in portal pressure through decreased splanchnic blood flow and decreased portocollateral resistance (66,67). Carvedilol has also been shown to be superior to other beta-blocking agents in reducing the hepatic venous pressure gradient (66,68).…”