- Pre-endoscopic administration of PPIs in patients with nonvariceal upper GI bleeding is still of controversial efficacy. It downstages the severity of the endoscopic signs of recent bleeding and may reduce the requirement for endoscopic hemostatic therapy at index endoscopy. However, there is no evidence of an effect on mortality, rebleeding, or surgical intervention rates. In contrast, the efficacy of PPIs in endoscopically diagnosed peptic ulcer bleeding is supported by high-quality evidence from numerous RCTs and meta-analyses of RCTs. PPIs compared with H2RAs or placebo consistently reduce rebleeding rates regardless of dose, route of administration, application or not of endoscopic hemostatic treatment, and geographic location. Surgical intervention rates and the need for further endoscopic hemostatic treatment are also reduced by PPI treatment, although the results are not as robust as those for rebleeding. There is no evidence of an overall effect of PPI treatment on all-cause mortality. However, all-cause mortality is reduced among patients with high-risk endoscopic signs and among trials that had been conducted in Asia. The optimal dose and route of PPI administration has yet to be determined.