title: Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension.
abstract: OBJECTIVE
  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.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Youn Zoo
authors.initials: YZ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Na
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Hyun Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Hyoun A
authors.initials: HA
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Sang Ok
authors.initials: SO
authors.lastname: Kwon
authors.affiliation: Department of Radiology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Cha
authors.affiliation: Department of Radiology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy*; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D011446:Prospective Studies; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D011433:Propranolol; C081643:candesartan
keywords: Angiotensin receptor blocker; Cirrhosis; Hepatic venous pressure gradient; Non-selective beta blocker; Portal hypertension