After Proper Optimization of Carvedilol dose, do Different Child Classes of Liver Disease Differ in Terms of dose Tolerance and Response on a Chronic Basis? (original) (raw)
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Acute and chronic haemodynamic and renal effects of carvedilol in patients with cirrhosis
Journal of Hepatology, 1999
Recent reports have suggested that the vasodilating beta-blocker carvedilol may have beneficial acute haemodynamic effects in cirrhotic portal hypertension. However, no data exist on chronic use or renal effects in this patient group. The aim of this study was to assess the acute and chronic haemodynamic and renal effects of carvedilol in cirrhotic patients. Seventeen cirrhotic patients (mean age 55.2+/-2.8, mean Child-Pugh score 7.4+/-0.5) were studied. Hepatic venous pressure gradient, cardiac output, systemic vascular resistance, mean arterial pressure, heart rate and hepatic blood flow were measured before and 1 h after 25 mg carvedilol. After 4 weeks of therapy with carvedilol 25 mg daily, these measurements were repeated before and after rechallenge with carvedilol. Urine volume, sodium excretion and creatinine clearance were also measured before and after 4 weeks of therapy. Seven patients did not complete the 4-week carvedilol therapy due to hypotension or poor compliance. Hepatic venous pressure gradient fell by 20.8% acutely (p<0.001) and by 16.3% after 4 weeks of therapy (p<0.002). Heart rate, mean arterial pressure and cardiac output fell after acute administration of carvedilol, but only heart rate fell significantly after 4 weeks of treatment. Hepatic blood flow, urine volume, sodium excretion and creatinine clearance remained unchanged after therapy. Carvedilol has beneficial effects on splanchnic haemodynamics following acute and chronic administration in cirrhosis, without compromising hepatic blood flow or renal function. However, a substantial number of patients cannot tolerate 25 mg daily.
Alimentary Pharmacology and Therapeutics, 2002
The haemodynamic effects of propranolol have been well studied. Lebrec et al. demonstrated a greater than 20% reduction in the hepatic venous pressure gradient (HVPG) following the acute administration of propranolol, 1 but up to one-third of patients do not exhibit a portal hypotensive response. 2 This may be explained by a portal hypertensive model demonstrating that a rise in the portocollateral resistance accompanies the reduc-tion in portal blood¯ow, thus reducing the overall portal hypotensive response to propranolol. 3 Current evidence suggests that the goal of pharmacotherapy in reducing the risk of variceal haemorrhage is to achieve a fall in the HVPG to £ 12 mmHg 4 or a 20% 5 reduction from baseline values. The role of non-selective b-blockers in the primary prevention of variceal haemorrhage has been extensively studied. 6±14 Meta-analysis of these trials has clearly shown the bene®t of these drugs when compared with placebo. 15 However, many patients are intolerant to drug side-effects. a 1 antagonism has been investigated in three haemodynamic studies. 16±18 Impressive reductions in the HVPG were achieved and these were comparable with SUMMARY Background: Carvedilol is a non-selective vasodilating b-blocker with weak a 1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent. Aim: To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low-dose carvedilol.
Hepatology, 2002
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 < 0.001). The proportion of patients achieving an HVPG reduction ⩾20% or ⩽ 20 mm Hg was greater after carvedilol (54% vs. 23%; P < 0.05). Carvedilol, but not propranolol caused a significant decrease in mean arterial pressure (MAP) (– 11 ± 1% vs. – 5 ± 3%; P = 0.05) and a significant increase in plasma volume (PV) and body weight (11 ± 5% and 2 ± 1%, respectively; P < 0.05). Glomerular filtration rate (GFR) was unchanged with either drug, but the dose of diuretics was increased more frequently after carvedilol (27% vs. 8% P = 0.07). 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. (HEPATOLOGY2002;36:1367–1373).
Carvedilol or propranolol in portal hypertension? A randomized comparison
Scandinavian Journal of Gastroenterology, 2012
Objectives. Carvedilol is a non-selective b-blocker with intrinsic anti-a 1 -adrenergic activity, potentially more effective than propranolol in reducing hepatic venous pressure gradient (HVPG). We compared the long-term effect of carvedilol and propranolol on HVPG and assessed whether the acute response to oral propranolol predicted the long-term HVPG response on either drug. Material and methods. HVPG was measured in 38 patients with cirrhosis and HVPG ‡ 12 mm Hg at baseline and then again 90 min after an oral dose of 80 mg propranolol. Patients were double-blinded randomized to either carvedilol (21 patients) or propranolol (17 patients) and after 90 days of treatment HVPG measurements were repeated. Results. HVPG decreased by 19.3 ± 16.1% (p < 0.01) and by 12.5 ± 16.7% (p < 0.01) in the carvedilol and propranolol groups, respectively, with no significant difference between treatment regimens (p = 0.21). Although insignificant, an acute decrease in HVPG of ‡12% was the best cut-off value to predict long-term HVPG response to propranolol when using ROC curve analysis.
Digestive and Liver Disease, 2014
Background and aims: Newer studies suggest that carvedilol, a beta-blocker with a moderate antialpha-1 activity, is superior to propranolol in reducing the portal pressure and risk of variceal bleeding. The effect on arterial blood pressure is a matter of concern especially in decompensated patients. Aims: to assess potential differential effects of beta-blockers and beta-blockers with moderate anti-alpha-1 activity on selected haemodynamic, humoral, and respiratory characteristics in cirrhosis. Methods: Patients with cirrhosis and portal hypertension were randomised to receive carvedilol (n = 16) or propranolol (n = 13). Cardiac, systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months. Results: Arterial blood pressure, heart rate, and cardiac output decreased equally, central circulation time and systemic vascular resistance increased significantly but similarly. Central blood volume, plasma volume and arterial compliance were unaltered. The QT c interval and renin levels decreased in the carvedilol group, however not significantly different from the propranolol group. Arterial oxygen saturation and alveolar arterial oxygen gradient remained constant in both groups. Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups (−17% and −20%, non significant). Conclusions: Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could not demonstrate any significant difference between the two treatments.
Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites
Journal of Hepatology, 2017
Background and aims: Carvedilol, a non-selective beta-blocker (NSBB) with additional antialpha 1 receptor activity, is a potent portal hypotensive agent. It has been used as prophylaxis against variceal bleed. However, its safety in decompensated liver cirrhosis with ascites is still disputed. In this study, we examined whether long-term use of carvedilol in the presence of ascites is a risk factor for mortality. Methods: This was a single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1 st of January 2009 to 31 st August 2012. The primary outcome was all-cause and liver-specific mortality in patients receiving or not receiving carvedilol as prophylaxis against variceal bleeding. Results: The final cohort after propensity score matching comprised 264 patients. Baseline ascites severity and UK End Stage Liver Disease (UKELD) score between carvedilol (n=132) and noncarvedilol (n=132) groups were comparable. Median follow-up time was 2.3 years. Survival at the end of the follow-up was 24% and 2% for carvedilol and non-carvedilol group respectively (Log Rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (Log Rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 [CI 0.44, 0.80] (p=0.001), suggesting 41% reduction in mortality risk. When stratified as per the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 [0.29, 0.77] (p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk. Conclusion: Long-term carvedilol therapy is not harmful in decompensated cirrhosis with ascites.
Annals of hepatology
Carvedilol appears to be more effective than propranolol in the treatment of portal hypertension in cirrhotic patients. Aim. To compare the effects of carvedilol vs. propranolol on systemic and splanchnic haemodynamics and to evaluate the adverse events associated with these treatments. We performed a systematic review following the Cochrane and PRISMA recommendations. Randomised controlled trials comparing carvedilol versus propranolol, in the treatment of portal hypertension in cirrhotic patients with oesophageal varices, with or without bleeding history were included. The primary outcome measure was the haemodynamic response to treatment. Four randomised trials and 153 patients were included; 79 patients received carvedilol (6.25-50 mg/d) and 74 patients received propranolol (10-320 mg/d). The hepatic vein pressure gradient (HVPG) decreased more with carvedilol than with propranolol (MD -2.21; 95% CI: -2.83 to -1.60, I(2) = 0%, P < 0.00001). Carvedilol was superior to proprano...
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2010
OBJECTIVE To assess the effect of Carvedilol in reducing portal pressure estimated non-invasively by studying Doppler ultrasound waveforms (DUS) and hepatic vein Damping Index (DI). STUDY DESIGN Quasi-experimental study. PLACE AND DURATION OF STUDY Department of Medical ICU in collaboration with Department of Radiology, JPMC, over a period of 6 months (June 1st to 30th November, 2008). METHODOLOGY Of the enrolled 65 patients, 47 patients (33 males and 14 females) completed the study. The mean age was 47.4 years. Cirrhotic patients of Hepatitis B, C, D (delta), B and C combined, B and D combined with varying degrees of portal hypertension were included in the study. Cirrhotic patients with bronchial asthma, congestive heart failure, Insulin dependent Diabetes, portal vein thrombosis and hepatorenal syndrome were excluded from the study. The patients were examined by color flow Doppler of the right hepatic vein before and after administration of Carvedilol. Their waveforms and Damping...