Jae Hyun Kim1, Jung Min Kim1, Youn Zoo Cho1, Ji Hoon Na1, Hyun Sik Kim1, Hyoun A Kim1, Hye Won Kang1, Soon Koo Baik2, Sang Ok Kwon1, Seung Hwan Cha3, Young Ju Kim3, Moon Young Kim2. 1. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. 2. Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. ; Department of Cell Therapy and Tissue Engineering, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea. 3. Department of Radiology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Abstract
BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. METHODS:Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. RESULTS: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P = 0.674]. The response rate (55.6% vs. 61.5%, P = 0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. CONCLUSIONS: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
RCT Entities:
BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. METHODS: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. RESULTS: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P = 0.674]. The response rate (55.6% vs. 61.5%, P = 0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. CONCLUSIONS: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
Authors: Moon Young Kim; Ki Tae Suk; Soon Koo Baik; Hyoun A Kim; Young Ju Kim; Seung Hwan Cha; Hwa Ryun Kwak; Mee Yon Cho; Hong Jun Park; Hyo Keun Jeon; So Yeon Park; Bo Ra Kim; Jin Heon Hong; Ki Won Jo; Jae Woo Kim; Hyun Soo Kim; Sang Ok Kwon; Sei Jin Chang; Gwang Ho Baik; Dong Joon Kim Journal: Hepatology Date: 2012-07-12 Impact factor: 17.425
Authors: J González-Abraldes; A Albillos; R Bañares; L R Del Arbol; E Moitinho; C Rodríguez; M González; A Escorsell; J C García-Pagán; J Bosch Journal: Gastroenterology Date: 2001-08 Impact factor: 22.682
Authors: M Schepke; E Werner; E Biecker; P Schiedermaier; J Heller; M Neef; B Stoffel-Wagner; U Hofer; W H Caselmann; T Sauerbruch Journal: Gastroenterology Date: 2001-08 Impact factor: 22.682
Authors: Juan Turnes; Juan Carlos Garcia-Pagan; Juan G Abraldes; Manuel Hernandez-Guerra; Alessandra Dell'Era; Jaime Bosch Journal: Am J Gastroenterol Date: 2006-03 Impact factor: 10.864