Portal pressure response to losartan compared with propranolol in patients with cirrhosis

De, Binay K; Bandyopadhyay, Kausik; Das, Tapas; Das, Debasish; Biswas, Pranab Kumar; Majumdar, Debabrata; Mandal, S. K.; Ray, Sujay; Dasgupta, Shyamal

doi:10.1016/s0002-9270(03)00277-6

Cited by 7 publications

(11 citation statements)

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“…Some studies showed benefit effect 14 , 15 but other papers showed that ARB was not appropriate to clinical use because of hazard effects such as hypotension and renal impairment with 26 or without portal pressure reduction. 14 , 15 , 26 , 27 As mentioned above, in the all previous study ARB was applied alone, and the effective dose was too high and resulted many complications such as renal impairment. Therefore in the present study we tried to compare ARB and NSBB combination therapy with NSBB monotherapy for the first time.…”

Section: Discussionmentioning

confidence: 99%

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

Kim

Cho

et al. 2014

Clin Mol Hepatol

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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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Section: Discussionmentioning

confidence: 99%

“… 13 However, AT1-R blockers alone did not show better effect than NSBB through many previous studies. 11 , 14 , 15 , 16 Therefore, this study aimed to identify the combination effect of ARB and NSBB comparing with NSBB monotherapy in reducing of PH.…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Cho

et al. 2014

Clin Mol Hepatol

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“…Encouraging results were also obtained with the AA spironolactone [ 83 , 84 ] and with ARB/ ACEi therapy, in which significant reductions in HVPG compared with a placebo were reported [ 75 , 76 , 79 , 85 ]. Although greater reductions in HVPG were achieved with NSBBs than with ARBs/ACEis, the difference according to the pooled individual patient data was not significant [ 77 , 80 ]. The HVPG of Child-Pugh class A patients treated with ARBs/ACEis or NSBBs decreased by 17% and 21%, respectively, whereas there was no significant change in the HVPG of Child-Pugh class B/C patients treated with ARBs/ACEis (3%) [ 61 ].…”

Section: Ras Antagonists For the Treatment Of Hepatic Fibrosis And Pomentioning

confidence: 99%

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

Shim

Eom

Kim

et al. 2018

Korean J Intern Med

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The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1–7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1–7)/Mas receptor and ACE2/Ang-(1–9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

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“…Accordingly, progression of liver fibrosis in hepatitis C virus positive patients is significantly decreased after treatment with angiotensin-converting enzyme inhibitors [ 137 ]. AT II is crucially involved in the manifestations of renal fibrosis by induction of pro-fibrotic effector molecules and EMT resulting in enhanced ECM production [ 138 ], and inhibition of AT II using angiotensin-converting enzyme (ACE) inhibitors or blocking agents towards the AT I receptor has emerged as a therapeutic approach to slow down renal disease progression [ 139 ] and revealed anti-fibrotic actions in the lung, heart and liver [ 140 - 143 ]. Interestingly, all components of the RAS have been detected in the human colonic mucosa [ 144 ] and AT II is increased in the mucosa of CD patients [ 145 ].…”

Section: Reviewmentioning

confidence: 99%

Medical therapy of stricturing Crohn’s disease: what the gut can learn from other organs - a systematic review

Bettenworth

Rieder

2014

Fibrogenesis Tissue Repair

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Crohn’s disease (CD) is a chronic remitting and relapsing disease. Fibrostenosing complications such as intestinal strictures, stenosis and ultimately obstruction are some of its most common long-term complications. Despite recent advances in the pathophysiological understanding of CD and a significant improvement of anti-inflammatory therapeutics, medical therapy for stricturing CD is still inadequate. No specific anti-fibrotic therapy exists and the incidence rate of strictures has essentially remained unchanged. Therefore, the current therapy of established fibrotic strictures comprises mainly endoscopic dilation as well as surgical approaches. However, these treatment options are associated with major complications as well as high recurrence rates. Thus, a specific anti-fibrotic therapy for CD is urgently needed. Importantly, there is now a growing body of evidence for prevention as well as effective medical treatment of fibrotic diseases of other organs such as the skin, lung, kidney and liver. In face of the similarity of molecular mechanisms of fibrogenesis across these organs, translation of therapeutic approaches from other fibrotic diseases to the intestine appears to be a promising treatment strategy. In particular transforming growth factor beta (TGF-β) neutralization, selective tyrosine kinase inhibitors, blockade of components of the renin-angiotensin system, IL-13 inhibitors and mammalian target of rapamycin (mTOR) inhibitors have emerged as potential drug candidates for anti-fibrotic therapy and may retard progression or even reverse established intestinal fibrosis. However, major challenges have to be overcome in the translation of novel anti-fibrotics into intestinal fibrosis therapy, such as the development of appropriate biomarkers that predict the development and accurately monitor therapeutic responses. Future clinical studies are a prerequisite to evaluate the optimal timing for anti-fibrotic treatment approaches, to elucidate the best routes of application, and to evaluate the potential of drug candidates to reach the ultimate goal: the prevention or reversal of established fibrosis and strictures in CD patients.

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Portal pressure response to losartan compared with propranolol in patients with cirrhosis

Cited by 7 publications

References 0 publications

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

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

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

Medical therapy of stricturing Crohn’s disease: what the gut can learn from other organs - a systematic review

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