From the Guidelines
Beta blockers are recommended for patients with variceal bleeding to reduce the risk of rebleeding and improve survival. Specifically, non-selective beta blockers like propranolol or nadolol should be started as soon as variceal bleeding is controlled, typically at an initial dose of 20-40 mg twice daily for propranolol or 20-40 mg once daily for nadolol, as supported by the study 1. The dose is then gradually increased to achieve a 25% reduction in resting heart rate or a heart rate of 55-60 beats per minute. These medications work by decreasing portal pressure through two mechanisms:
- Reducing cardiac output (beta-1 effect)
- Causing splanchnic vasoconstriction (beta-2 effect) By lowering portal pressure, beta blockers reduce the risk of variceal rupture and subsequent bleeding. The most recent and highest quality study 1 suggests that the combination of endoscopic variceal ligation (EVL) plus a non-selective beta blocker (NSBB) is the primary treatment for preventing esophageal variceal rebleeding, as it has been shown to decrease the rebleeding rate and tend to decrease the mortality rate during follow-up. In patients with contraindications to beta blockers (e.g., severe asthma, heart failure), endoscopic band ligation can be considered as an alternative for preventing rebleeding. Regular follow-up is necessary to monitor for side effects and ensure optimal dosing, with the goal of reducing the hepatic venous pressure gradient (HVPG) by at least 20% or to 12 mmHg or less, as this has been shown to significantly reduce the risk of variceal rebleeding 1.
From the Research
Mechanism of Action
- Beta blockers work by blocking beta1 receptors, reducing cardiac output, and blocking beta2 receptors, producing splanchnic vasoconstriction and reducing portal flow, consequently reducing portal pressure 2
- The reduction in portal pressure is achieved by decreasing the hepatic venous pressure gradient (HVPG) to less than 12 mmHg or by more than 20% from baseline 2, 3
Efficacy in Primary Prophylaxis
- Non-selective beta blockers reduce the bleeding risk from 30 to 15% in primary prophylaxis 2
- Beta blockers reduce the risk of first variceal bleeding by 50% compared to no treatment 4
- The acute hemodynamic response to beta-blockers can be used to predict the long-term risk of first bleeding, with an HVPG reduction of more than 10% from baseline being the best target to define response in primary prophylaxis 3
Comparison with Other Therapies
- Variceal band ligation (VBL) is very effective in preventing the initial bleed when compared to no treatment, but it is not superior to beta-blockers 4
- Combined therapies, including beta-blockers and other treatments, do not demonstrate significant improvements in variceal bleeding, total upper gastrointestinal bleeding, and mortality compared to monotherapies 5
- The combination of isosorbide-mononitrate or spironolactone with non-selective beta-blockers tends to decrease the risk of variceal bleeding when compared with the use of non-selective beta-blockers alone 5