Patients who survive an episode of acute variceal hemorrhage are at high risk of recurrence. Overall, 60% of these individuals will rebleed within 2 years with a mortality rate of 33% [4
]. Therapy aimed at reducing this risk is essential and should be implemented as soon as the initial hemorrhage is controlled [9
]. Multiple modes of treatment have been investigated including monotherapy with nonselective beta
-blockers, combination medical therapy, EVBL with or without pharmacological adjunct, and TIPS.
-blockers have been shown to decrease rebleeding rates from 60% to 42-43% likely secondary to the decrease in portal pressure [4
]. Further portal pressure reduction can be achieved when they are combined with oral nitrates (ISMN) [38
]. Nitrate-induced venodilation decreases cardiac output and blood pressure, which can lead to a baroreceptor-mediated splanchnic vasoconstriction and fall in portal pressure [39
]. It may also have a direct vasodilatory effect on the portosystemic circulation; however, a randomized trial and a recent meta-analysis did not show any benefit in adding a nitrate. In addition, combined therapy is associated with more adverse effects leading to discontinuation of treatment [40
In terms of endoscopic therapy, EVBL is superior to sclerotherapy and is the method of choice [42
]. Meta-analysis of several randomized controlled trials (719 patients) comparing EVBL versus combination medical therapy, with nonselective beta
-blockers and nitrates, showed no difference in rebleeding rate and increased survival in the medically treated group [44
]. Also, two prospective trials suggest that the combination of EVBL with medical therapy (nadolol) may be superior to EVBL alone [48
]. The use of EVBL and a nonselective beta
-blocker is the current recommendation for secondary prophylaxis and should be instituted without delay following initial bleed [10
]. However, a recent randomized controlled trial looking at combination therapy (EVBL + nadolol + nitrate) versus medical therapy alone (nadolol + nitrate) found no difference in rebleeding rates, need for rescue therapy, or mortality while the combination therapy was associated with more adverse events [50
]. More studies will be needed to confirm these findings but future guidelines may move towards medical therapy alone.
Finally, TIPS in secondary prophylaxis has been shown to lower rebleeding rates when compared to the aforementioned medical/endoscopic therapy [51
]. However, no mortality benefit has been demonstrated with TIPS and its use is associated with higher costs and incidence of hepatic encephalopathy. Therefore, the use of TIPS in secondary prophylaxis is not recommended; however, its use may be considered following failure with conventional medical therapy [10
]. This may change with the advent of polytetrafluoroethylene- (PTFE-) covered prostheses, which substantially improves TIPS patency.
In summary, EVL in combination with nonselective beta-blockers is the method of choice in preventing recurrent variceal bleeding. The addition of nitrates can theoretically potentiate the portal pressure drop; however, it has not been shown to decrease mortality or rebleeding rates and is associated with greater side effects. TIPS is not recommended for secondary prophylaxis and should only be considered following failure with usual medical therapy. It decreases rebleeding rates without a mortality benefit while being associated with higher costs and incidence of hepatic encephalopathy. Whether the new PTFE covered stent will improve TIPS efficacy in secondary prophylaxis remains to be seen, but for the moment its use is restricted to those cases where other therapies have failed.