Clinical and Molecular Hepatology (Dec 2014)

Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension

  • Jae Hyun Kim,
  • Jung Min Kim,
  • Youn Zoo Cho,
  • Ji Hoon Na,
  • Hyun Sik Kim,
  • Hyoun A Kim,
  • Hye Won Kang,
  • Soon Koo Baik,
  • Sang Ok Kwon,
  • Seung Hwan Cha,
  • Young Ju Kim,
  • Moon Young Kim

DOI
https://doi.org/10.3350/cmh.2014.20.4.376
Journal volume & issue
Vol. 20, no. 4
pp. 376 – 383

Abstract

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Background/AimsAngiotensin 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.MethodsBetween 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.ResultsThe 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.ConclusionsThe 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.

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