Propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: Long-term hemodynamic and renal effects

Abstract

The effect on kidney function, vasoactive systems and ascites outcome of long-term treatment with propranolol plus isosorbide-5-mononitrate, a combined therapy proven more effective than propranolol alone in decreasing portal pressure in the cirrhotic patient, is unknown. Thirty cirrhotic patients who survived acute variceal bleeding and were treated with propranolol plus isosorbide-5-mononitrate were studied. Portal and systemic hemodynamics (n = 15), inulin clearance, free water clearance, plasma renin activity, aldosterone concentration and prostaglandin E2 excretion (n = 20) were measured before and after 3 mo of treatment. In addition, data on ascites outcome in the entire series after a mean follow-up of 9.6 mo were compared with those of 30 patients undergoing elective sclerotherapy and with those of 30 patients treated with propranolol alone matched for age, sex, presence of ascites, Child-Pugh class and mean follow-up length included in other randomized controlled trials. Combined therapy significantly decreased the hepatic venous pressure gradient and azygos blood flow. In addition, no changes in inulin clearance, free water clearance, plasma renin activity, aldosterone concentration and prostaglandin E2 excretion occurred, despite a mild decrease in mean arterial pressure. Moreover, no differences among the three groups of patients studied in ascites outcome were found. These results suggest that long-term treatment with propranolol plus isosorbide-5-mononitrate does not impair kidney function, vasoactive systems or ascites outcome in cirrhotic patients.

Effect of Losartan, An Angiotensin Ii Receptor Antagonist, on Portal Pressure in Cirrhosis

“…6,7,[27][28][29] Preliminary results of a long-term follow-up including 26 patients of the present study show that the portal pressure-lowering effect of losartan is sustained at 6 months of continual treatment (Table 4). Feu et al demonstrated a relation between the portal hemodynamic response to pharmacotherapy and the decrease in the risk of variceal rebleeding in patients with cirrhosis.…”

“…3 However, the average reduction in portal pressure by 15% achieved with ␤-blockers is moderate, 4 and no relevant decrease is observed in more than 30% of patients despite adequate dosage. 5 To enhance the pressure-lowering effect on portal hypertension, ␤-blockers are combined with isosorbide-5 mononitrate, 6 an agent that reduces portal pressure in cirrhosis because of its vasodilator properties. 7 One study demonstrated a mean reduction in portal pressure of 19% during therapy with the combination of propranolol and isosorbide-5 mononitrate.…”

“…7 One study demonstrated a mean reduction in portal pressure of 19% during therapy with the combination of propranolol and isosorbide-5 mononitrate. 6 In patients with sodium retention and ascites, however, serious deterioration of renal function was observed with the combination of ␤-blockers and nitrates. 8 The limited effect on portal pressure, the incidence of adverse effects-15% for nonselective ␤-blockers alone, 9 16% for nadolol plus isosorbide-5 mononitrate 10 -and the timeconsuming dose-finding are a stimulant for the search for new antihypertensive substances.…”

Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis

“…Indeed, in a clinical trial comparing isosorbide mononitrate alone versus propranolol alone, Angelico et al 6 reported a shorter survival in patients treated with isosorbide mononitrate, when patients older than 50 years were considered, and conflicting reports are available on the long-term effects of the combination of ␤-blockers plus nitrates on the risk of ascites occurrence. [7][8][9] In two recent trials, currently published only as abstracts, a marginally significant decrease in the rate of bleeding was observed in one, 10 and no difference was seen in the other, 11 and a tendency to increase in ascites occurrence was observed in the former 10 but not in the latter. 11 Here, we report the long-term results of our trial after extending the observation period until 7 years.…”

Nonselective β–Blockers Plus Nitrates in Portal Hypertension: An Open Question

“…This confirms previous studies with shorter follow-up. 23,24 Both studies are also concordant on the lack of difference in mortality, but no conclusion can be drawn on this point, since the size of these studies, designed to assess the effect on bleeding rate, was definitely too small to assess possible differences in mortality rates.…”