Variceal bleeding is a common and often severe complication in patients with cirrhosis and portal hypertension.
Once such bleeding occurs it is a high resource-consuming event that is associated with a high mortality rate, which in the most recent series has approached 25%.
β-blockers have been shown to effectively prevent first variceal bleeding (FVB) in cirrhotic patients. However, these drugs are not effective in the treatment of all patients.
The addition of isosorbide-mononitrate (Is-Mn) to non-selective β-blockers has therefore been suggested to improve the clinical efficacy of these drugs.
This combined therapy promotes a greater reduction in portal pressure, almost double that which can be achieved with the use of β-blockers alone.
Several studies have strongly suggested that this combined therapy is the treatment of choice for the secondary prevention of variceal bleeding.
In the treatment of primary variceal bleeding, however, the evidence supporting the use of β-blockers and Is-Mn in combination is controversial.
A combined analysis of 3 separate studies, involving 522 patients, found no significant differences in the prevention of first bleeding and mortality between patients administered the combination therapy, or those given β-blockers alone.
Furthermore, in some patients with ascites, the use of β-blockers can be precluded by the high rate of contraindications and side effects.
In this situation, Is-Mn alone, with its ability to reduce portal hypertension as a long-acting vasodilator, has been put forward as an alternative to β-blockers in the prevention of FVB.
Researchers in Italy have therefore compared the efficacy and applicability of nadolol and isosorbide-mononitrate in preventing FVB in a population of cirrhotic patients at high risk of variceal bleeding with ascites, who can be frequently intolerant to β-blockers.
A total of 80 consecutive cirrhotic patients with ascites and esophageal varices (25% average risk of bleeding at 1 year) were considered.
28 of these patients were excluded from taking further part in the study due to contraindications, and the remaining 52 were randomly assigned to receive either nadolol (n = 25) or Is-Mn (n = 27).
| Is-Mn - offers no protection against FVB in cirrhotic patients |
|Journal of Hepatology|
The researchers found the frequency of contraindications was greater for β-blockers than Is-Mn (35% versus 0%).
During 21.3 ±11.6 months of follow-up, side effects forced 6 patients taking nadolol and 4 taking Is-Mn to stop treatment.
Bleeding occurred in 2 patients taking nadolol and 10 taking Is-Mn.
The probability of bleeding was significantly lower in the nadolol group whereas overall survival was similar between both groups. A total of 7 patients on Is-Mn and 8 on nadolol died.
Dr Gianmario Borroni, one of the authors of the report, commented that, perversely, in patients with ascites, Is-Mn is tolerated but ineffective while nadolol is effective but less tolerated.
In an accompanying editorial on the alternatives to non-selective β-blockers in the treatment of FVB in the same issue of the journal, Dr Juan Carlos Garcia-Pagan said that the study by Borroni et al. "clearly showed that Is-Mn does not offer any protection against first variceal bleeding in patients with cirrhosis."