Comparison Of Short-term Effect Of Carvedilol And Propranolol In The Reduction Of HVPG In Patients With Cirrhotic Portal Hypertension

Background and Objective:Nonselective β-blockers propranolol is the first choice of drugs to reduce portal hypertension clinically, but up to1/2-1/3of portal hypertension patients may not respond appropriately to propranolol. Carvedilol has both strong nonselective β receptors antagonist and a weak a (?)-receptor antagonist activity, and it is considered to be an effective drug with potential significance that can decrease portal vein pressure and prevent the hemorrhage of varices. Hepatic vein pressure gradient (HVPG) is the gold standard for the evaluation of treatment effects of portal hypertension, choice of treatments and judgments of prognosis in the international. At present, whether the effect of carvedilol reducing HVPG or its side effects are better than propranolol is still controversial. There are less domestic studies on direct comparisons of carvedilol and propranolol in reducing portal hypertension, as well as clinical evaluations of carvedilol. In addition, what are the influence factors for the effect of the nonselective β-blockers is still uncertain. The objective of our study is to discuss the problems above preliminarily by the comparison of short-term effect of carvedilol and propranolol in the reduction of HVPG in patients with cirrhotic portal hypertension.Methods:Sixty-four patients with liver cirrhosis were randomly divided into two groups, one group taking propranolol (n=33, starting dose of10mg, tid), another group taking carvedilol (n=31, starting dose is12.5mg, qd). All the patients were monitored of blood pressure and heart rate everyday. And then the dosage was adjusted according to the changes of blood pressure and heart rate, promising the heart rate decreased to20%-25%of the baseline but not less than55beats/min, and the blood pressure not less than90/60mmHg. HVPG and the index of renal function of the two groups of patients were all measured at the baseline before the drugs were administered orally, and again7days after carvedilol or propranolol administered, respectively."Responders" were defined as those with HVPG reduction at least20%from baseline or lowering HVPG to below12mmHg. Then we compared the HVPG reduction and safety of7-day use of carvedilol and propranolol, and observed whether there would be symptomatic hypotension, ascites, renal function damage, and so on.Results:Both carvedilol and propranolol could make great reduce of HVPG, but carvedilol caused a greater decrease in HVPG than propranolol (28.30+22.19%vs.12.38±24.09%; p=0.026). The proportion of patients achieving an HVPG reduction≥20%or≤12mmHg was greater after carvedilol (56.7%vs.41.9%, respectively), but not significantly (p=0.250). Carvedilol reduced mean arterial pressure (MAP) greater than propranolol (10.06±8.73%vs.6.46±12.56%; p=0.031), no obvious difference between the heart rate. Serum creatinine and urea nitrogen were unchanged with carvedilol, and patients also have no generation or worsen trend of ascites, which indicated that carvedilol has no significant damages to kidney. Patients of Child-Pugh class B/C had higher response rate than those of Child-Pugh class A (64.3%vs.31.3%, respectively, p=0.040) in the group with carvedilol treatment, indicating that patients who are most likely to respond to carvedilol therapy were those with more advanced liver disease. Patients with moderate or severe varices could be reduced HVPG significantly (19.15±27%vs.-4.44±41.4%, respectively, p=0.038), and had higher response rate than mild varices(56.0%vs.18.2%, respectively, p=0.023), so were patients with severe portal hypertension(the reduction of HVPG was20.22±23.46%and6.41±18.11%respectively, p=0.021), showing that the severity of varices and portal hypertension may influence the effect of nonselective β-blockers reducing the HVPG.Conclusions:1. Both of carvedilol and propranolol can reduce HVPG significantly, but carvedilol is much more apparent;2. Carvedilol reduces mean arterial pressure (MAP) greater than propranolol, but it has no significant hypotension and damages to kidney in short term use;3. Patients who are most likely to respond to carvedilol therapy were those with more advanced liver disease (Child-Pugh B and C);4. The severity of varices and baseline of HVPG may influence the effect of nonselective β-blockers reducing the hepatic vein pressure gradient.