Primary Prophylaxis for Non-Bleeding Esophageal Varices in Cirrhosis
For patients with medium or large esophageal varices who have not bled, either non-selective beta-blockers (propranolol, nadolol, or carvedilol) or endoscopic variceal ligation should be used for primary prophylaxis, with the choice based on patient characteristics and contraindications. 1
Treatment Options for Medium/Large Varices
The American Association for the Study of Liver Diseases establishes that any of the following therapies are appropriate first-line options 1:
Non-Selective Beta-Blockers (NSBBs)
NSBBs significantly reduce the risk of first variceal bleeding from 30% in untreated patients to 14% in treated patients, preventing one bleeding episode for every 10 patients treated. 1, 2
Specific dosing regimens 1:
Propranolol: Start 20-40 mg orally twice daily, adjust every 2-3 days
- Maximum: 320 mg/day in patients without ascites
- Maximum: 160 mg/day in patients with ascites
- Target: Resting heart rate 55-60 bpm, systolic BP ≥90 mmHg
Nadolol: Start 20-40 mg orally once daily, adjust every 2-3 days
- Maximum: 160 mg/day in patients without ascites
- Maximum: 80 mg/day in patients with ascites
- Target: Resting heart rate 55-60 bpm, systolic BP ≥90 mmHg
Carvedilol: Start 6.25 mg once daily
- After 3 days increase to 6.25 mg twice daily
- Maximum: 12.5 mg/day (except in persistent hypertension)
- Target: Systolic BP ≥90 mmHg
Endoscopic Variceal Ligation (EVL)
EVL is performed every 2-8 weeks until variceal eradication, with first surveillance endoscopy 3-6 months after eradication, then every 6-12 months thereafter. 1
Management of Small Varices
The approach differs based on bleeding risk stratification 1:
High-Risk Small Varices
NSBBs should be used in patients with small varices who have increased bleeding risk, defined as 1, 2:
- Child-Pugh class B or C cirrhosis, OR
- Presence of red wale marks on varices
Low-Risk Small Varices
For patients with small varices without high-risk features 1:
- NSBBs can be considered but long-term benefit is not established
- If NSBBs are not used, perform surveillance endoscopy every 2 years
- If hepatic decompensation occurs, perform endoscopy at that time and repeat annually
Patients on NSBBs for primary prophylaxis do not require serial surveillance endoscopy. 1
Important Clinical Considerations
Combination Therapy NOT Recommended
Combination therapy with NSBBs plus EVL is NOT recommended for primary prophylaxis, as one randomized trial showed no difference in bleeding or death between combination versus EVL alone, with expectedly higher side effects in the combination group. 1 This contrasts with secondary prophylaxis where combination therapy is standard. 2
Recent Evidence on Combination Therapy
A 2025 meta-analysis suggests combination therapy may reduce first bleeding episodes compared to monotherapy (9.4% vs 28.2% for NSBB alone, 9.4% vs 13.9% for EVL alone), but this contradicts current guideline recommendations and requires incorporation into future guidelines before clinical adoption. 3
Contraindications to Consider
TIPS placement is not recommended for prevention of first variceal hemorrhage, as surgical shunt trials showed significantly higher encephalopathy rates and tendency toward higher mortality. 1
Mechanism and Monitoring
NSBBs reduce portal pressure by decreasing cardiac output (β1-blockade) and producing splanchnic vasoconstriction (β2-blockade). 1 Hemodynamic responders (achieving HVPG ≤12 mmHg or ≥20% reduction from baseline) have significantly lower bleeding risk (relative risk 0.13) compared to non-responders. 4
Duration of Therapy
Prophylactic therapy with NSBBs should be continued indefinitely, as the risk of bleeding recurs when treatment is stopped. 1, 2
Special Population: Patients with Ascites
In patients with gross recurrent ascites and large varices, EVL as monotherapy may be preferred over NSBBs, with repeat EVL every 1-2 weeks until obliteration. 5 This represents a specific clinical scenario where endoscopic therapy takes precedence.