Gastrointestinal bleeding is most common cause of hospitalization in the United States among patients with digestive diseases [1]. Peptic ulcer disease, the most common cause of gastrointestinal bleeding, accounts for over $800 million annual expenditures in the United States [1]. Prior to the 1960s, peptic ulcer disease bleeding was primarily managed surgically. Since then, angiography, injection treatment, electrothermal coagulation, endoscopic clips, Helicobacter pylori testing, proton pump inhibitors, hemostatic sprays, and potassium-competitive acid blockers have expanded the therapeutic armamentarium used in the management of bleeding peptic ulcer disease (Fig. 1). Guidelines support the use of endoscopic clips or thermal therapy for actively bleeding ulcers or ulcers with nonbleeding visible vessels, reserving angiography and surgery for instances of rebleeding or failure of endoscopic hemostasis [2]. Nevertheless, access to endoscopic therapies for gastrointestinal bleeding is subject to disparities, with lower rates of endoscopy among rural or minority populations. Furthermore, real-world utilization and hemostasis success rates of endoscopy, angiography, and surgical techniques remain unknown [3].

Fig. 1
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Timeline of innovations in gastrointestinal bleeding

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In this issue of Digestive Diseases and Sciences, Mujadzic et al. [4] analyzed 136,425 hospitalizations in the 2018 National Inpatient Sample (NIS) to characterize mortality, hemostasis success rate, and resource utilization (charges, costs, and length of hospitalization) for peptic ulcer bleeding hospitalizations. Endoscopic therapy was used in 33.6% of admissions, with repeat endoscopy performed in 27.2% of hospitalizations. Radiologic and surgical therapies were less commonly used, at 1.4% and 0.1%, respectively. Endoscopy had the highest rates of hemostasis (95.1%), followed by radiologic (89.1%) and surgical interventions (66.7%). Endoscopic hemostasis was defined as surviving the hospitalization and not undergoing additional endoscopic, radiologic-guided embolization, or surgical therapy. Overall, in-hospital mortality was 1.9%, increasing to 11.1% after failed endoscopic hemostasis. Though duodenal ulcers were associated with lower rates of successful endoscopic hemostasis, they were associated with higher odds of multiple endoscopies, radiology-guided embolization, and longer hospitalizations, compared with gastric ulcers.

There are several limitations to this study, including the inability to account for Helicobacter pylori status, coagulopathy, and use of anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), or antiplatelet agents, all of which may affect the success of hemostasis. Furthermore, data on stigmata of recent bleeding (i.e., active bleeding, nonbleeding visible vessel, adherent clot, pigmented spot, or clean ulcer base) or choice of endoscopic therapy (i.e., clips, thermal therapy, epinephrine injection, or hemostatic powders) are lacking. The inability to assess these variables hampers any attempt to draw firm conclusions on the appropriate use of endoscopic therapy for peptic ulcers, since suboptimal adherence to guidelines, including failure to perform endoscopic hemostasis when indicated, was reported in a national cohort study of nonvariceal upper gastrointestinal bleeding [5]. Of note, 27.2% of hospitalizations included more than one upper endoscopy. Unfortunately, the purpose of multiple endoscopic evaluations is unclear since repeat endoscopy may have been performed due to inadequate visualization during the index endoscopy, rebleeding, or a routine second-look endoscopy, the latter of which is no longer recommended by international guidelines [6]. Although the study used the NIS to obtain a national perspective, the NIS does not encompass all hospitalizations. Since most hospitalizations in the study were located in urban teaching hospitals, these may not represent practice or outcomes at rural or non-teaching hospitals. Furthermore, this study does not apply to in-hospital bleeding, since the study population was limited to individuals with peptic ulcer bleeding as their primary diagnosis.

Despite the plethora of effective interventions for peptic ulcer hemostasis, rebleeding rates continue to vary, and gaps in care persist. Notably, only 64.8% of hospitalizations in this study included an endoscopy within 24 h of admission, a metric supported by guidelines [2]. This finding is in line with a Canadian audit of upper gastrointestinal bleeding hospitalizations, which noted a 65.6% rate of endoscopy within 24 h, though lower than a Danish national study which noted an 82% rate of endoscopy within 24 h of suspected peptic ulcer bleeding [5, 7]. The authors noted superior endoscopic hemostasis success rates and lower mortality rates for peptic ulcer bleeding, which may be related to advances in endoscopic hemostasis, including the recent addition of over-the-scope clips or their newer definition of hemostasis that ignores recurrent signs of overt bleeding (i.e., hematemesis, melena, hematochezia), hemodynamic changes, or hemoglobin decline, factors that have traditionally characterized rebleeding and inadequacy of hemostasis [8]. This study noted inferior outcomes in patients who underwent radiologic-guided embolization or surgery. Since guidelines recommend the use of angiography or surgery for refractory ulcer bleeding, the low rates of hemostasis from radiologic-guided embolization and surgery reported in this study may be related to selection of a specific population of patients who undergo these non-endoscopic interventions as salvage therapy for bleeding ulcers refractory to endoscopic therapy. This study also adds to the growing evidence of continued decline in peptic ulcer disease-related mortality rates, which was lower than previous mortality rates noted using the NIS [9].

In conclusion, this article presents an updated analysis of hemostatic therapies for peptic ulcer bleeding, providing essential data for clinicians to counsel patients regarding the efficacy and costs of endoscopy, surgery, or angiography to manage peptic ulcer bleeding. Since 2018, the year of data that were analyzed in this study, the Food and Drug Administration (FDA) approved several hemostatic powders and gels, and vonoprazan, a potassium-competitive acid blocker that provides more potent acid suppression compared with proton pump inhibitors. The impact of these new tools on ulcer hemostasis, mortality, and resource utilization is uncertain but worthy of further exploration. Treatment of peptic ulcer disease is constantly evolving, and with further advances in medicine, endoscopy, angiography, and surgery, the future of ulcer hemostasis is bright.