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

Abstract

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.

Portal Hypertension and Related Complications: Diagnosis and Management

“…Although a mild reduction in portal pressure has been observed, inhibition of the RAAS results in a clinically significant decrease in systemic arterial pressure and higher rates of renal dysfunction. [21][22][23][24] Therefore, ARBs, either as monotherapy or combined with NSBB, is not recommended in the management of portal hypertension. Transient portal pressure reduction has also been observed with administration of octreotide, a somatostatin analogue with potent splanchnic vasoconstrictive effects.…”

Decreased potency of fimasartan in liver cirrhosis was quantified using mixed-effects analysis

“…Patients with cirrhosis had significantly higher predrug plasma ACE and renin activity than that in healthy controls. [16] There are a few reports regarding the higher activity of ACE and renin in patients with cirrhosis, [1,17] and all of our subjects with moderate hepatic dysfunction were diagnosed as having liver cirrhosis. Therefore, we speculate that augmented BP lowering effects are not likely to occur in patients A B Fimasartan potency in liver cirrhosis TCP Transl Clin Pharmacol with liver cirrhosis following 120 mg of fimasartan despite their higher exposure to the drug.…”

“…[1] Fimasartan is a nonpeptide angiotensin II receptor blocker with a selective type 1 receptor blocking effect. [2] It is rapidly absorbed after oral administration with a peak plasma concentration at 0.5-3.0 h, [3] and its exposure is dose proportional with a terminal elimination half-life ranging from 5 to 16 h in healthy subjects.…”

Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study

“…7 However, many patients do not reach the treatment target, since only 30% to 50% of patients achieve a hemodynamic response to NSBB therapy, which is an important limitation of NSBB. 5 , 8 , 9 …”