Why is propranolol (beta-blocker) used in the management of esophageal varices?

Why Propranolol is Used in Esophageal Varices

Propranolol is used in esophageal varices because it reduces portal pressure through dual mechanisms—decreasing cardiac output (β1 blockade) and producing splanchnic vasoconstriction (β2 blockade)—which significantly reduces the risk of first variceal bleeding from 30% to 14%, preventing one bleeding episode for every 10 patients treated. 1, 2

Mechanism of Portal Pressure Reduction

Nonselective beta-blockers like propranolol work through two complementary pathways that directly address the pathophysiology of portal hypertension:

• β1 blockade decreases cardiac output, reducing blood flow into the portal system 1
• β2 blockade produces splanchnic vasoconstriction, which is the more important mechanism, reducing portal blood flow 1
• The therapeutic goal is achieving a hepatic venous pressure gradient (HVPG) reduction to <12 mmHg or a ≥20% reduction from baseline, which essentially eliminates hemorrhage risk and improves survival 1, 2

Important caveat: Selective beta-blockers (atenolol, metoprolol) are less effective and suboptimal for variceal prophylaxis because they lack the critical β2-mediated splanchnic vasoconstriction. 1, 2

Clinical Efficacy in Primary Prophylaxis

The evidence for propranolol's effectiveness is robust and guideline-supported:

• Meta-analysis of 11 trials (1,189 patients) demonstrated that nonselective beta-blockers reduce first variceal bleeding from 30% in controls to 14% in treated patients 1
• Mortality is also significantly lower in the beta-blocker group compared to controls 1
• Cost-effectiveness analysis shows beta-blockers are the only cost-effective form of prophylactic therapy compared to sclerotherapy and shunt surgery 1

Specific Indications for Primary Prophylaxis

Propranolol should be initiated in:

• Patients with medium/large varices who have never bled 1, 2
• Patients with small varices at high risk (Child B/C cirrhosis or red wale marks on varices) 2
• Nonselective beta-blockers can slow progression from small to large varices, reducing progression from 37% to 11% at 3 years 2

Dosing Strategy

The dosing approach has evolved based on evidence showing heart rate reduction doesn't correlate with HVPG reduction:

• Starting dose: 40 mg once daily 1, 3
• Titration: Increase to maximal tolerated dose rather than targeting a specific heart rate reduction 1, 2
• Long-acting propranolol can be used at 80-160 mg daily to improve compliance 2, 3
• Special consideration: In patients with ascites, maximum dose should be reduced to 160 mg daily (versus 320 mg in those without ascites) 3

Comparison with Endoscopic Variceal Ligation (EVL)

While propranolol is highly effective, the evidence comparing it to EVL shows equipoise:

• Multiple large randomized trials demonstrate that EVL is equivalent to propranolol in preventing first variceal hemorrhage 1, 4, 5
• One trial showed EVL superiority (15% bleeding vs 43% with propranolol at 18 months), but this was not consistently replicated 6
• Expert consensus: Both nonselective beta-blockers and EVL are effective; the decision should be based on patient characteristics, preferences, local resources, and expertise 1
• Propranolol should be offered when EVL is not feasible or when patients prefer medical therapy 5

Secondary Prophylaxis

For patients who have already bled:

• Combination therapy of nonselective beta-blockers plus EVL is the best option for secondary prophylaxis 2
• Beta-blockers should be continued indefinitely once started, as discontinuation increases bleeding and mortality risk 2, 3

Contraindications and Monitoring

Absolute contraindications include:

• Asthma or severe COPD 2, 3
• Heart block 2, 3
• Significant bradycardia 2, 3
• Hypotension 2, 3
• Decompensated heart failure 2, 3

Monitoring requirements:

• Regular assessment of heart rate, blood pressure, and renal function, particularly in end-stage liver disease 2, 3
• In patients with refractory ascites or spontaneous bacterial peritonitis, close monitoring is essential 3

Common Pitfall to Avoid

Do not use combination therapy with isosorbide mononitrate (ISMN) for primary prophylaxis. While one non-blinded trial showed benefit, two larger double-blind placebo-controlled trials failed to confirm efficacy and showed greater side effects. 1 Similarly, adding spironolactone to nadolol does not increase efficacy in primary prophylaxis. 1