A Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy of Carvedilol vs. Propranolol to Reduce Portal Pressure in Patients with Liver Cirrhosis

Sang G. Kim, Tae Y. Kim, Joo H. Sohn, Soon H. Um, Yeon S. Seo, Soonkoo Baik, Moonyoung Kim, Jae Y. Jang, Soung W. Jeong, Bora Lee, Young S. Kim, Ki T. Suk, Dong J. Kim

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES:Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis. More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient (HVPG) than propranolol. The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol.METHODS:A total of 110 patients with a baseline HVPG value >12 mm Hg were allocated randomly to receive either carvedilol or propranolol. The HVPG measurement was repeated after 6 weeks of daily medication. The primary end point was a ≥20% fall in HVPG compared with baseline or <12 mm Hg.RESULTS:The difference in the proportion of responders in the carvedilol (49.1%) vs. propranolol (30.9%) groups did not reach statistical significance in the intention-to-treat analysis (P=0.08). However, among patients with a model for end-stage liver disease (MELD) score ≥15, carvedilol resulted in a significantly greater response than that of propranolol (7/12, 58.3% vs. 0/10, 0%; P=0.005). Similarly, carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 (46.2 vs. 0%; P=0.046). The presence of ascites also had a significant influence on the response rate (51.5 vs. 24.2%; P=0.042). A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons (P=0.005). Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different.CONCLUSIONS:Overall, carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient. However, this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to understand the relative risk benefit.

Original languageEnglish
Pages (from-to)1582-1590
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume111
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1

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Portal Pressure
Propranolol
Liver Cirrhosis
Venous Pressure
End Stage Liver Disease
Liver
Intention to Treat Analysis
carvedilol
Drug-Related Side Effects and Adverse Reactions
Ascites
Fibrosis
Hemodynamics
Hemorrhage
Costs and Cost Analysis

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Kim, Sang G. ; Kim, Tae Y. ; Sohn, Joo H. ; Um, Soon H. ; Seo, Yeon S. ; Baik, Soonkoo ; Kim, Moonyoung ; Jang, Jae Y. ; Jeong, Soung W. ; Lee, Bora ; Kim, Young S. ; Suk, Ki T. ; Kim, Dong J. / A Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy of Carvedilol vs. Propranolol to Reduce Portal Pressure in Patients with Liver Cirrhosis. In: American Journal of Gastroenterology. 2016 ; Vol. 111, No. 11. pp. 1582-1590.
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abstract = "OBJECTIVES:Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis. More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient (HVPG) than propranolol. The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol.METHODS:A total of 110 patients with a baseline HVPG value >12 mm Hg were allocated randomly to receive either carvedilol or propranolol. The HVPG measurement was repeated after 6 weeks of daily medication. The primary end point was a ≥20{\%} fall in HVPG compared with baseline or <12 mm Hg.RESULTS:The difference in the proportion of responders in the carvedilol (49.1{\%}) vs. propranolol (30.9{\%}) groups did not reach statistical significance in the intention-to-treat analysis (P=0.08). However, among patients with a model for end-stage liver disease (MELD) score ≥15, carvedilol resulted in a significantly greater response than that of propranolol (7/12, 58.3{\%} vs. 0/10, 0{\%}; P=0.005). Similarly, carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 (46.2 vs. 0{\%}; P=0.046). The presence of ascites also had a significant influence on the response rate (51.5 vs. 24.2{\%}; P=0.042). A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons (P=0.005). Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different.CONCLUSIONS:Overall, carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient. However, this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to understand the relative risk benefit.",
author = "Kim, {Sang G.} and Kim, {Tae Y.} and Sohn, {Joo H.} and Um, {Soon H.} and Seo, {Yeon S.} and Soonkoo Baik and Moonyoung Kim and Jang, {Jae Y.} and Jeong, {Soung W.} and Bora Lee and Kim, {Young S.} and Suk, {Ki T.} and Kim, {Dong J.}",
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A Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy of Carvedilol vs. Propranolol to Reduce Portal Pressure in Patients with Liver Cirrhosis. / Kim, Sang G.; Kim, Tae Y.; Sohn, Joo H.; Um, Soon H.; Seo, Yeon S.; Baik, Soonkoo; Kim, Moonyoung; Jang, Jae Y.; Jeong, Soung W.; Lee, Bora; Kim, Young S.; Suk, Ki T.; Kim, Dong J.

In: American Journal of Gastroenterology, Vol. 111, No. 11, 01.11.2016, p. 1582-1590.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy of Carvedilol vs. Propranolol to Reduce Portal Pressure in Patients with Liver Cirrhosis

AU - Kim, Sang G.

AU - Kim, Tae Y.

AU - Sohn, Joo H.

AU - Um, Soon H.

AU - Seo, Yeon S.

AU - Baik, Soonkoo

AU - Kim, Moonyoung

AU - Jang, Jae Y.

AU - Jeong, Soung W.

AU - Lee, Bora

AU - Kim, Young S.

AU - Suk, Ki T.

AU - Kim, Dong J.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - OBJECTIVES:Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis. More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient (HVPG) than propranolol. The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol.METHODS:A total of 110 patients with a baseline HVPG value >12 mm Hg were allocated randomly to receive either carvedilol or propranolol. The HVPG measurement was repeated after 6 weeks of daily medication. The primary end point was a ≥20% fall in HVPG compared with baseline or <12 mm Hg.RESULTS:The difference in the proportion of responders in the carvedilol (49.1%) vs. propranolol (30.9%) groups did not reach statistical significance in the intention-to-treat analysis (P=0.08). However, among patients with a model for end-stage liver disease (MELD) score ≥15, carvedilol resulted in a significantly greater response than that of propranolol (7/12, 58.3% vs. 0/10, 0%; P=0.005). Similarly, carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 (46.2 vs. 0%; P=0.046). The presence of ascites also had a significant influence on the response rate (51.5 vs. 24.2%; P=0.042). A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons (P=0.005). Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different.CONCLUSIONS:Overall, carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient. However, this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to understand the relative risk benefit.

AB - OBJECTIVES:Propranolol has been used as prophylaxis for variceal bleeding in patients with cirrhosis. More recent data suggest that carvedilol may be more effective for reducing the hepatic venous pressure gradient (HVPG) than propranolol. The primary aim of this study was to evaluate the hemodynamic response to carvedilol compared with propranolol.METHODS:A total of 110 patients with a baseline HVPG value >12 mm Hg were allocated randomly to receive either carvedilol or propranolol. The HVPG measurement was repeated after 6 weeks of daily medication. The primary end point was a ≥20% fall in HVPG compared with baseline or <12 mm Hg.RESULTS:The difference in the proportion of responders in the carvedilol (49.1%) vs. propranolol (30.9%) groups did not reach statistical significance in the intention-to-treat analysis (P=0.08). However, among patients with a model for end-stage liver disease (MELD) score ≥15, carvedilol resulted in a significantly greater response than that of propranolol (7/12, 58.3% vs. 0/10, 0%; P=0.005). Similarly, carvedilol was superior to propranolol in patients with Child-Pugh score ≥9 (46.2 vs. 0%; P=0.046). The presence of ascites also had a significant influence on the response rate (51.5 vs. 24.2%; P=0.042). A MELD score ≥15 was the only significant predictor of response among these post hoc groups after adjusting for multiple comparisons (P=0.005). Severe adverse events were higher in the carvedilol group although drug-associated adverse events were not different.CONCLUSIONS:Overall, carvedilol offered no clear advantage over propranolol but it may be more effective in advanced cirrhotic patients with a MELD score≥15 in reducing the portal pressure gradient. However, this potential benefit may come with a cost of increased risk of side-effects and outcome data over a longer term is needed to understand the relative risk benefit.

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DO - 10.1038/ajg.2016.327

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EP - 1590

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 11

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