Treatment of Esophageal Varices With Carvedilol

Kurt J. Isselbacher


AccessMedicine from McGraw-Hill 

Nonselective beta blockers or endoscopic band ligation (EVL) are recommended for primary prophylaxis of variceal bleeding in patients with esophageal varices. However, it has been found that additional α-adrenergic blockade with carvedilol may increase the number of patients with hemodynamic responses resulting in a reduction in hepatic venous pressure gradient (HVPG) of >20% or to values of <12 mmHg.

The nonselective ß-adrenergic blockers (NSBBs) propranolol and nadolol have been the mainstay in the pharmacologic treatment of portal hypertension for the last 30 years. Their beneficial effects have been closely associated with their ability to decrease HVPG, achieving a good HVPG response in about 30–40% of patients with a reduction in bleeding of about 50%. In addition, the HVPG response to NSBBs may be enhanced by adding drugs that decrease the hepatic vascular tone with such agents as isosorbide mononitrate (ISMN). The use of ISMN plus NSBBs leads to response in an additional one-third of HVPGs nonresponders, with a corresponding decrease in their bleeding risk.

Carvedilol was introduced several years ago. This drug has intrinsic anti α-adrenergic activity, resulting in a greater decrease in HVPG than either propranalol or nadolol—and thus appears to be a promising agent in the treatment of portal hypertension.

A new report by Reiberger and colleagues (2013) provides data on the use of carvedilol for the prophylaxis of first variceal bleeding. They demonstrated that carvedilol is more powerful than propranolol in decreasing HVPG, and it achieves a good HVPG response with a reduction of >20% baseline or <12 mmHg in 56% of patients who failed to respond to propranolol. They also showed that a low dose of carvedilol (e.g., <25 mg per day) is as effective as higher doses (e.g., 25–50 mg per day) at decreasing HVPG, with a lower risk of causing arterial hypotension. Finally, their study showed that the use of this drug is successful in maintaining a lower risk of variceal bleeding and of clinical decompensation.

In an accompanying editorial, Dr. Jamie Bosch (2013) asks whether these data should be taken as evidence that carvedilol at present is the beta blocker of choice. He suggests that such a case can be made, at least in patients considered for primary prophylaxis who are not hypotensive and do not have refractory ascites. He also suggests that if the safety of carvedilol is confirmed in larger studies, it would be appropriate to start therapy directly with carvedilol instead of propranolol.