Why does Nonsteroidal Anti-Inflammatory Drug (NSAID) use cause variceal bleeding?

From the Guidelines

Non-selective beta-blockers (NSBBs) are the cornerstone of treatment for preventing variceal bleeding in patients with portal hypertension and esophageal varices, as they reduce portal pressure through decreasing cardiac output and causing splanchnic vasoconstriction, thereby reducing blood flow to the portal system. The primary NSBBs used are propranolol (starting at 20mg twice daily, titrated up to maximum tolerated dose) and nadolol (starting at 20-40mg once daily) 1. These medications are indicated for primary prevention in high-risk patients (those with medium/large varices or small varices with red signs or Child-Pugh C) and for secondary prevention in all patients who have previously bled.

• Key benefits of NSBBs include:
  • Reduced risk of variceal bleeding
  • Decreased portal pressure
  • Improved survival
• Key considerations for NSBB use include:
  • Dose titration to achieve a 25% reduction in resting heart rate or a target heart rate of 55-60 beats per minute, while maintaining systolic blood pressure above 90mmHg
  • Monitoring for common side effects such as fatigue, dizziness, and sexual dysfunction
  • Contraindications, including asthma, severe COPD, heart block, and hypotension
• Alternative treatments, such as endoscopic variceal ligation, may be considered for patients who cannot tolerate NSBBs, although the combination of NSBBs and ligation provides the best protection against rebleeding 1.

From the Research

NSBB Variceal Bleeding

• Non-selective beta-blockers (NSBB) are commonly used for primary prevention of esophageal variceal bleeding in patients with cirrhosis 2, 3, 4.
• Studies have shown that NSBB can decrease the risk of first variceal bleeding and all-cause mortality in patients with cirrhosis and large esophageal varices 2.
• However, the effectiveness of NSBB in preventing variceal bleeding in patients with small esophageal varices is still unclear, with some studies suggesting that NSBB may not be effective in preventing growth of small varices 5.
• The choice of treatment for primary prevention of variceal bleeding depends on various factors, including the size of the varices, the presence of other complications, and the patient's overall health status 6, 4.

Risk Factors for Variceal Bleeding

• Several factors can increase the risk of variceal bleeding in patients with cirrhosis, including:
  • Age: younger patients may be at higher risk of variceal bleeding 3
  • Presence of ascites: patients with ascites may be at higher risk of variceal bleeding 3
  • Medical comorbidity: patients with greater medical comorbidity may be at higher risk of variceal bleeding 3
  • MELD score: patients with higher MELD scores may be at higher risk of variceal bleeding 3, 6
  • Esophageal variceal diameter: patients with larger esophageal varices may be at higher risk of variceal bleeding 6

Comparison of Treatment Options

• NSBB and endoscopic variceal ligation (EVL) are two commonly used treatments for primary prevention of variceal bleeding 2, 6, 4.
• Studies have shown that EVL may not be significantly more effective than NSBB in preventing variceal bleeding in patients with cirrhosis and gastric varices 6.
• However, EVL may be associated with a higher risk of serious adverse events compared to NSBB 2.
• Carvedilol, a type of NSBB, may be more effective than traditional NSBB in preventing variceal bleeding in some patients 2, 4.