Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate in the treatment of portal hypertension

Albillos, Agustı́n; García–Pagán, Juan–Carlos; Iborra, Jerónimo; Bandi, Juan Carlos; Cacho, Guillermo; Pérez–Paramo§, María; Escorsell, Àngels; Calleja, José Luís; Escartín, P; Bosch, Jaime

doi:10.1016/s0016-5085(98)70372-5

Cited by 101 publications

(74 citation statements)

References 19 publications

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“…The second situation is the patient who fails to exhibit an adequate decrease of HVPG during treatment with propranolol or nadolol. Available pharmacological options in this setting are the association of a second drug (isosorbide mononitrate, 1,30 prazosin, 31 or simvastatin 32 ) or to shift to carvedilol (if there are no contraindications and the patient is not hypotensive). 21 All the mentioned alternatives, except the association of simvastatin, carry the risk of causing hypotension, and the only one with which there is a large experience is with isosorbide mononitrate that can ''rescue'' about one-third of propranolol nonresponders.…”

Section: Recommendationsmentioning

confidence: 99%

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: Recommendationsmentioning

confidence: 99%

Carvedilol for Portal Hypertension in Patients With Cirrhosis

Bosch

2010

Hepatology

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“…The combination of beta-blockers with prazosin caused a greater decrease in portal pressure than betablockers alone [17,18], increasing the proportion of hemodynamic responders to over 80%. According to these relevant hemodynamic finding a recent trial has examined the usefulness of a HVPG guided therapy with betablockers plus prazosin [19].…”

Section: Potential Clinical Utility Of Risk Stratificationmentioning

confidence: 99%

Prognostic Markers in Patients Who Have Recovered from an Acute Variceal Bleeding: Role of HVPG Measurement

et al. 2011

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“…16 Combined treatment with b-blockers and prazosin induces a greater reduction in HVPG than achieved with b-blockers and ISMN, increasing the rate of response to 85%, one of the highest reported to date. 17 Concerns have been raised about the safety of prazosin because this drug enhances peripheral arterial vasodilation and induces hypotension favouring sodium and water retention, 18,19 although these effects are attenuated by the addition of b-blockers. 17 It has not been assessed whether a careful titration of prazosin in patients already treated with b-blockers may be effective to rescue nonresponders to b-blockers and ISMN, while simultaneously avoiding adverse effects.…”

Section: Introductionmentioning

confidence: 99%

“…17 Concerns have been raised about the safety of prazosin because this drug enhances peripheral arterial vasodilation and induces hypotension favouring sodium and water retention, 18,19 although these effects are attenuated by the addition of b-blockers. 17 It has not been assessed whether a careful titration of prazosin in patients already treated with b-blockers may be effective to rescue nonresponders to b-blockers and ISMN, while simultaneously avoiding adverse effects. 16 This randomized study aimed to investigate whether the association of b-blockers and prazosin may rescue nonresponders to b-blockers and ISMN and to assess the value of this HVPG-guided therapy for preventing variceal rebleeding compared to a control group treated with the current recommended therapy combining b-blockers and endoscopic variceal ligation (EVL).…”

Section: Introductionmentioning

confidence: 99%