Carvedilol, a new nonselective beta-blocker with intrinsic anti-alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis

Bañares, Rafael; Moitinho, Eduardo; Piqueras, B.; Casado, Marta; García–Pagán, Juan–Carlos; Diego, Alejandro; Bosch, Jaume

doi:10.1002/hep.510300124

Cited by 167 publications

(175 citation statements)

References 36 publications

(51 reference statements)

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“…1 However, the vasodilating activity of carvedilol may enhance arterial hypotension and sodium retention, a risk which is especially relevant in patients with advanced, decompensated cirrhosis. 19,20,21 Drugs that inhibit cytochrome P450 2D6 activity (quinidine, paroxetine, fluoxetine, propafenone) may increase plasma concentrations of R-carvedilol (a stereoisomer with alpha-and beta-adrenergic blocking activity). In contrast, plasma concentrations of S-carvedilol (which has only beta-blocker activity) increase much less.…”

Section: Carvedilolmentioning

confidence: 99%

“…In contrast, plasma concentrations of S-carvedilol (which has only beta-blocker activity) increase much less. 19 Thus, these drugs increase the risk of hypotension during carvedilol administration. Patients Carvedilol is a potent nonselective beta-blocker, and as such, it decreases heart rate and cardiac index (blockade of beta-1 adrenergic receptors) and causes splanchnic vasoconstriction (blockade of beta-2 adrenergic receptors), which result in a reduced portal blood flow, and thereby in decreased portal pressure.…”

Section: Carvedilolmentioning

confidence: 99%

“…Patients older than 65 years have a delayed clearance of carvedilol, as do patients with chronic liver disease. 19,21 Therefore, it is advised that carvedilol should be started at low doses (6.25 mg/day). If tolerated, the dose is increased stepwise up to a maximum of 25 mg twice daily (50 mg in patients weighing >85 kg).…”

Section: Carvedilolmentioning

confidence: 99%

“…If tolerated, the dose is increased stepwise up to a maximum of 25 mg twice daily (50 mg in patients weighing >85 kg). 19,21 Titration should be done slowly, increasing the dose at intervals of 1-2 weeks. The drug should be taken with food to slow the speed of absorption and reduce the likelihood of side effects.…”

Section: Carvedilolmentioning

confidence: 99%

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Carvedilol for portal hypertension in patients with cirrhosis

Bosch

2010

Hepatology

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A 48-year-old male with hepatitis C-related cirrhosis is found on endoscopy to have large esophageal varices with red signs. He has never previously had variceal bleeding, and there is no evidence of hepatic encephalopathy. He does have mild ascites. Comorbidity includes diabetes which has been present for many years and is well-controlled on a stable dose of insulin. He has no cardiopulmonary disease. The hemoglobin is 12.4 g/dL, white blood cell count is 6800/mm 3 , and platelets are 112 Â 10 9 /L. Serum bilirubin is 1.8 mg/ dL, creatinine is 1.2 mg/dL, international normalized ratio is 1.3, and the serum albumin is 3.5 g/dL. The electrocardiogram and chest x-ray are normal. The ultrasound examination does not show portal vein thrombosis or hepatocellular carcinoma.What is the role of carvedilol in the prevention of variceal bleeding in this patient? How will the dose of carvedilol be adjusted and how is the patient to be monitored for adverse drug events? When would carvedilol be preferred over nadolol or propranolol? Would the approach be different if the patient was of Child-Pugh class C cirrhosis? The ProblemPortal hypertension is an almost unavoidable complication of cirrhosis, and provides the driving force for most of its complications, such as esophageal and gastric varices, variceal bleeding, portal hypertensive gastropathy, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, thrombopenia, leukopenia and anemia, and portal-systemic encephalopathy.1 Recent studies have shown that for these complications to develop, the portacaval pressure gradient-evaluated clinically by the hepatic venous pressure gradient (HVPG)-should increase above 10 mm Hg and should be above 12 mm Hg for variceal bleeding. 2,3The prevalence of varices is about 40% in asymptomatic compensated patients.2 Development of varices follows an incidence of approximately 6% per year. The incidence is nearly double in patients with a baseline HVPG >10 mm Hg, who therefore represent a high-risk group.2 These patients are also at higher risk of developing decompensation (ascites, bleeding, jaundice, encephalopathy) and hepatocellular carcinoma. 4,5 Because of this, there is a great interest in strategies to revert portal hypertension, since these would prevent portal hypertension-related complications, clinical decompensation, and death. The benefit of reduction of HVPG has actually been proven for patients exhibiting a ''good hemodynamic response'' to nonselective beta-adrenergic blockers; i.e., those who exhibit a decrease in HVPG > 20% of baseline or to values below 12 mm Hg during continued therapy, 6,7 or who show a decrease in HVPG >10% of baseline 20 minutes after an intravenous infusion of propranolol. 8,9 Besides the increased intravascular pressure, the risk of bleeding from varices is further influenced by other factors, such as the diameter of the varices and the thickness of the variceal wall.10 These factors are interrelated by Laplace's law in the concept of wall tension (t), according to which: t ¼ variceal tran...

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Section: Carvedilolmentioning

confidence: 99%

Section: Carvedilolmentioning

confidence: 99%

Section: Carvedilolmentioning

confidence: 99%

Section: Carvedilolmentioning

confidence: 99%

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Carvedilol for portal hypertension in patients with cirrhosis

Bosch

2010

Hepatology

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“…Also, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduced cardiac index and MAP resulting in worsened outcomes in patients with advanced cirrhosis and ascites [40][41][42][43] . Finally, other studies of newer-generation beta-blockers such as carvedilol showed that although carvedilol may be more potent than propranolol in terms of reducing portal hypertension, it was associated with more systemic hypotension, increase in plasma volume and body weight, and worsening of preexisting ascites [44][45][46][47] .…”

Section: Blood Pressure and Cirrhosismentioning

confidence: 99%

Non-Selective Beta-Blockers in Liver Cirrhosis: Friends or Foes? A Review of the Literature

Abboud

Tabet

2016

Journal of Gastroenterology and Hepatology Research

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in cirrhosis, and try to provide logical suggestions concerning the use of this class of medication in patients with cirrhosis. INTRODUCTIONCirrhosis is becoming a leading cause of mortality and morbidity worldwide [1,2] , and since 1981, beta-blockers were found to be highly efficacious in both, primary and secondary prevention of variceal bleeding [3] . Non-selective beta-blockers (NSBB) became the cornerstone of the medical treatment of patients with cirrhosis [3] , and this was demonstrated in several solid studies. However, recent evidence has questioned the use of beta-blockers in patients with end-stage liver disease and refractory ascites [3] . In this article, we are going to review almost all the previous studies about beta-blocker therapy in patients with cirrhosis, and find out the beneficial effects of this therapy, its potential complications and harms, and try to provide suggestions regarding its appropriate use in this specific category of patients. CIRRHOSISCirrhosis represents an advanced stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. It is normally considered to be irreversible in its late stages at which point the only therapeutic ABSTRACTCirrhosis has become a leading cause of death in the United States and worldwide owing the increased prevalence of alcoholic liver disease, hepatitis C, and more recently, non-alcoholic steatohepatitis and nonalcoholic fatty liver disease. Beta-blockers have been proven to be efficacious in primary, as long as secondary prophylaxis of variceal bleeding, more than 35 years ago. Nonetheless, recent data has cautioned the use of beta-blockers in patients with end-stage cirrhosis and refractory ascites suggesting increased mortality from betablockers in this group of patients. In this article, we will discuss this topic in details, and review the conflicting studies about beta-blockers REVIEW

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