Non-selective beta-blockers (NSBBs) lower portal pressure and are key in the primary and secondary prevention of variceal bleeding and preventing the first episode of decompensation.

Key concepts

• Portal hypertension is the main abnormal mechanism that occurs in cirrhosis and the main cause of decompensation (e.g., ascites, varices)
• Non-selective beta-blockers such as carvedilol, propranolol, or nadolol* may be used to reduce portal pressure
• The use of NSBBs lowers the risk of first variceal bleed and also helps to prevent recurrent variceal hemorrhage
• In patients with compensated cirrhosis, NSBBs could prevent development of ascites
• Lowering portal pressure in patients with compensated cirrhosis decreases the risk of decompensation (e.g., ascites, hepatic encephalopathy, variceal bleeding) and death
• In patients with refractory ascites and low systolic blood pressure (<90 mmHg or mean arterial pressure <65 mmHg) NSBBs may increase the risk of hypotension, renal dysfunction and death

Key recommendations

• NSBBs (e.g., carvedilol, propranolol, nadolol*) are recommended for patients with compensated cirrhosis and Clinically Significant Portal Hypertension (CSPH)**
• If patients are unable or unwilling to take NSBBs and have large varices, endoscopic variceal ligation (EVL) to obliteration is recommended
• NSBB plus EVL is recommended for patients with a history of variceal hemorrhage
• Carvedilol should be avoided in patients with ascites, unless the patient has hypertension

NSBBs prevent first variceal hemorrhage

• Many randomized controlled trials (RCTs) have demonstrated that NSBBs prevent first variceal hemorrhage in patients with CSPH
• This benefit is independent of the presence or absence of ascites
• Many RCTs have demonstrated that NSBBs appear to be as effective as EVL in preventing first variceal hemorrhage
• Available data suggests that carvedilol is equally effective as EVL in preventing first variceal hemorrhage
• Carvedilol more potently lowers portal pressure than other NSBBs.

NSBBs prevent recurrent variceal hemorrhage

• Many RCTs have demonstrated that NSBB plus EVL is the most effective therapy in the prevention of recurrent variceal hemorrhage
• In Child-Turcotte-Pugh class B and C patients who have recovered from variceal hemorrhage, EVL alone is associated with a higher mortality rate compared with combination NSBBs plus EVL

NSBBs in patients with ascites or spontaneous bacterial peritonitis

• NSBB use in patients with cirrhosis with diuretic refractory ascites or spontaneous bacterial peritonitis has demonstrated worsening renal function and higher mortality if the systolic BP is <90 mmHg or mean arterial pressure is <65 mmHg.
• In those with ascites, nadolol* maximum dose should be reduced to 80 mg daily and propranolol maximum dose to 80 mg twice daily while carvedilol should be avoided

*Nadolol is not offered on the VA formulary but can be obtained with a nonformulary request

**CSPH Defined as:

• Liver Stiffness Measurement (LSM) >25kPa OR
• LSM >20 kPa <25kPa AND platelets <150K OR
• LSM >15 kPa AND platelets <110K
• Any size varices on EGD OR
• Imaging with porto-systemic collaterals