A Cochrane review included 19 studies with a total of 2 033 subjects. 11 studies used a second injected agent, five used a mechanical method (haemoclips) and three employed thermal methods.
The risk of further bleeding after initial haemostasis was lower in the combination therapy groups than in the epinephrine alone group, regardless of which second procedure was applied (RR 0.53, 95% CI 0.35 to 0.81). Adding any second procedure significantly reduced the overall bleeding rate (persistent and recurrent bleeding) (RR 0.57, 95% CI 0.43 to 0.76) and the need for emergency surgery (RR 0.68, 95% CI 0.50 to 0.93). Mortality rates were not significantly different when either method was applied.
Adding a second procedure reduced further bleeding rate from 18.5% to 10% (RR 0.55, 95% CI 0.42 to 0.73), and emergency surgery from 10.8% to 6.7% (RR 0.69, 95% CI 0.51 to 0.95). Mortality fell from 4.7% to 2.5% (RR 0.52, 95% CI 0.38 to 1.05), without statistical significance. Subanalysis showed that the risk of further bleeding decreased regardless of which second procedure was applied. In addition, the risk was reduced in all subgroups.