Pharmacological Management of Peptic Ulcer Bleeding

Article information

Korean J Helicobacter Up Gastrointest Res. 2026;26(2):125-130

Publication date (electronic) : 2026 June 8

doi : https://doi.org/10.7704/kjhugr.2025.0075

Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon, Korea

Corresponding author Jun-Won Chung, MD, PhD Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, College of Medicine, Gachon University, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea E-mail: junwonchung@daum.net

Received 2025 October 31; Revised 2025 December 1; Accepted 2025 December 16.

Abstract

Peptic ulcer bleeding (PUB) is the most common cause of non-variceal upper gastrointestinal bleeding, although its incidence is decreasing worldwide. Current epidemiological evidence demonstrates the positive influence of Helicobacter pylori eradication on outcomes, owing to the widespread introduction of proton pump inhibitor (PPI) treatment. However, PUB is still commonly encountered in clinical settings given the increasing indications for nonsteroidal anti-inflammatory drugs, anticoagulants, and antiplatelet agents in the aging population. Regardless of advancements made in the endoscopic approach and pharmacological treatment, upper gastrointestinal bleeding has an inevitable mortality rate ranging from 7% to 11%. Endoscopic treatment is recommended for peptic ulcers with current bleeding, vessel exposure, or clotting. However, the development of effective high-dose PPIs has resulted in a decrease in rebleeding events after endoscopic treatment. Pharmacological management consisting of post-endoscopic treatment was more effective than pre-endoscopic treatment. As PPIs ensure that gastric acidity remains above pH 6, they are essential treatments for PUB. This review aimed to investigate the current strategies for PUB pharmacological management.

Keywords: Upper gastrointestinal tract; Peptic ulcer; Pharmacology

PEPTIC ULCER BLEEDING

Upper gastrointestinal bleeding (UGIB) is a commonly encountered clinical manifestation, with a global incidence of 47 per 100000 persons/year for non-variceal bleeding and a mortality rate ranging from 7% to 11% [1,2]. Moreover, UGIB is one of the most frequent causes of emergency hospital admission, with undeniable morbidity, mortality, and medical care costs [3,4]. Particularly, UGIB mortality incidence has remained unchanged despite endoscopic and pharmacologic advancements over the last decades.

Peptic ulcer bleeding (PUB) is the most common cause of UGIB, reaching an incidence of 43.6%, followed by gastritis and duodenitis (27.6%), esophageal variceal bleeding (8.0%), and esophagitis (5.6%) [5,6]. UGIB has a global incidence of 20 to 100 persons per 100000 each year, with a 30-day mortality rate between 5% and 10% [7-10].

The current overall decreasing trend demonstrates the influence of Helicobacter pylori eradication and widespread introduction of proton pump inhibitors (PPI). Nonetheless, PUB is still commonly encountered clinically, given the increasing indications for nonsteroidal anti-inflammatory drugs (NSAIDs), anticoagulation, and antiplatelet agent consumption associated with the aging population.

PUB clinical manifestations include hematemesis, melena, hematochezia, and occult blood, including clinical symptoms associated with blood deficits, such as dizziness, syncope, angina pectoris, and dyspnea.

The current management of bleeding includes fluid resuscitation, pharmacological therapy with acid inhibitors, endoscopic hemostatic treatment, and surgery. Overall, pharmacological treatment has focused on the inhibition of gastric acid secretion, facilitating clot formation, and stabilizing the clot, which has resulted in the successful outcomes of patients with PUB [11]. Antacids development has improved the symptomatic treatment of peptic ulcer disease, and the introduction of an H2 blocker has contributed to peptic ulcer therapy; however, these have limitations for the treatment of PUB. Effective suppression of gastric acid by PPI results in the improvement of peptic ulcers and PUB. PPI enables maintenance of gastric acid levels above pH 6 and prevents the aggregation of platelets and hemolysis caused by gastric acid and pepsin [12,13]. Therefore, suppressing gastric acid levels and elevating gastric pH results in a reduction of rebleeding risk, including effective hemostasis by platelet aggregation and inhibition of thrombolysis. This review aimed to investigate the current pharmacological management of PUB.

PHARMACOKINETICS OF MEDICAL TREATMENT FOR PUB

In PUB, the hemostatic process involves vasoconstriction, platelet aggregation, and coagulation. Platelet aggregation and coagulation are physiological defense mechanisms against rebleeding. Gastric acid and pepsin inhibit platelet aggregation and accelerate the degradation of an already coagulated thrombus. In particular, when gastric acid is below pH 5.4, platelet aggregation and plasma coagulation are inhibited, and pepsin accelerates the degradation of the coagulated thrombus [14]. Therefore, pharmacological treatment for PUB aims to control the level of gastric acidity to ensure proteolysis and improve the environment of the bleeding area [11]. The inhibition of gastric acid and pepsin results in the stabilization of the thrombus and promotes hemostasis to prevent rebleeding. Therefore, the pharmacological treatment goal of PUB is to enhance gastric acid levels above pH 6 [12,13]. H2 blockers have the limitation of reaching acid levels above pH 6; however, PPI development has enabled an increase in pH to approximately 6, resulting in an improvement in rebleeding.

PHARMACOLOGICAL TREATMENT FOR PUB

The therapeutic approach to patients with UGIB depends on its location, range, and bleeding rate. The maintenance of hemodynamic stability and intravascular volume is an important factor in the management of patients with bleeding. In the last few decades, pharmacological treatment of non-variceal UGIB has focused on strong acid suppression with PPI. Gastric acid disrupts the coagulation pathway and stimulates platelet aggregation and fibrinolysis. Therefore, suppressing acid secretion, elevating the pH level above 6, and maintaining this level stabilizes the coagulation pathway and decreases the tendency for rebleeding [12,13]. H2 blockers alone for patients with PUB have not achieved significant treatment outcomes owing to early resistance to medication. In contrast, PPIs, strong acid blockers, do not induce drug resistance and result in successful treatment outcomes.

The most recent guidelines on UGIB management, including the 2021 American College of Gastroenterology (ACG), 2021 European Society of Gastrointestinal Endoscopy (ESGE), and 2018 Asia-Pacific guidelines, emphasize pre- and post-endoscopic PPI therapy and long-term prevention with different focuses and treatment intensities [5,15,16].

Pre-endoscopic PPI is recommended as an optional pharmacological treatment in all guidelines, although the 2021 ACG guidelines stress that there is no benefit in terms of mortality based on recent clinical study outcomes. Furthermore, post-endoscopic high-dose PPI therapy for 3 days has been introduced in all guidelines, although the 2021 ACG guidelines distinguish intermittent high-dose PPI from continuous infusion. As a long-term prevention strategy, H. pylori eradication is commonly proposed, and both 2021 ESGE and 2018 Asia-Pacific guidelines strongly emphasize evaluation, including eradication even after a negative result on retesting of the initial infection [5].

Pre-endoscopic PPI therapy

For the initial management of pre-endoscopic medical therapy, the application of PPI may be considered [16]. Intravenous PPI (80 mg bolus followed by 8 mg per hour) may decrease the proportion of patients with a higher risk of hemorrhagic stigmata during endoscopy with endoscopic treatment. However, PPIs do not improve the possibility of clinical course, including additional bleeding, surgical management, and death [16].

Lau et al. [17] reported accelerated the resolution of bleeding in ulcers and reduction in necessity for therapeutic endoscopic approach by infusion of high-dose omeprazole before endoscopy with no increased incidence of bleeding or mortality. Sixty of the 314 patients included in the analysis (19.1%) in omeprazole group versus 90 of 317 patients (28.4%) (p=0.007) in the placebo group presented need for endoscopic treatment [17]. Patients with PPI treatment had less active bleeding ulcers (6.4% vs. 14.7%; p=0.01) and a much higher percentage of clean-based ulcers (64.2% vs. 47.4%; p=0.001) [17]. In contrast, to our knowledge, no evidence supported benefit in prevention of further bleeding (11/314 [3.5%] vs. 8/317 [2.5%]; difference=1%, -2% to 4%) or mortality (8/314 [2.5%] vs. 7/317 [2.2%]; difference=0%, -2% to 3%).

A systematic review of evidence from randomized controlled trials (RCTs) of PPI treatment initiated before endoscopy for UGIB was based on a Cochrane meta-analysis of six randomized trials with 2223 cases. No significant differences in mortality, rebleeding, or surgical outcomes were observed between the PPI and control groups. No significant differences were observed between the PPI and control treatments. Specifically, no significant differences were observed between patients treated with PPI and controls in terms of incidence of mortality (6.1% vs. 5.5%; odds ratio [OR]=1.12, 0.72–1.73) [18]. Similar results were achieved in outcomes of rebleeding events (13.9% vs. 16.6%; OR=0.81, 0.61–1.09) and surgery need (9.9% vs. 10.2%, OR=0.96, 0.68–1.35) [18].

Furthermore, Kanno et al. [19] updated the analysis with improved evidence grading and an extended search strategy of the previous study. Result has been similar with no reduction in mortality (OR 1.14, 95% confidence interval [CI] 0.76–1.70) and surgery (OR 0.91, 95% CI 0.65–1.26) [19].

Post-endoscopic PPI therapy

After reaching successful endoscopic hemostasis for ulcer bleeding, administration of ≥80 mg of daily as high-dose PPI therapy for ≥3 days continuously or intermittently achieves further reduction in bleeding events and mortality [16]. Continuous therapy is defined as an 80-mg bolus followed by an 8-mg/h infusion, whereas intermittent oral or intravenous therapy is suggested to be applied as an 80-mg bolus followed by 40 mg 2–4 times daily [16].

By analyzing seven RCTs with eight randomized comparisons of high-dose PPI therapy (≥80 mg daily for at least 3 days) and six RCTs with placebo (six RCTs) or no treatment (two comparisons in one RCT) after successful endoscopic hemostasis, PPI was shown to reduce further bleeding events (risk ratio [RR]=0.43, 0.33–0.56), mortality (RR=0.41, 0.22–0.79), and surgery (RR=0.42, 0.25–0.71) compared with placebo or no treatment [20-26]. No significant difference was observed in terms of treatment effects between continuous and intermittent PPI therapy on subgroup analysis, with the result (p≥0.90) [20-26].

A further analysis of nine RCTs comparing high-dose PPI therapy and histamine-2 receptor antagonist (H2RA) therapy after successful endoscopic hemostasis demonstrated significant improvement in further bleeding events in patients treated with PPI compared with those receiving H2RA therapy (RR=0.56, 0.41–0.77). However, no significant benefit has been made in the mortality rate or in the need for surgical management [26-34]. No significant difference in treatment effects was observed between continuous and intermittent PPI therapy in the subgroup analysis (p>0.90).

Further bleeding was significantly reduced by twice-daily PPI therapy until 2 weeks after the index endoscopy compared to once-daily PPI therapy in high-risk patients who underwent 3 days of high-dose PPI therapy post-endoscopy [26-34]. A single RCT enrolled 293 patients with PUB and high-risk Rockall scores ≥6, who had undergone endoscopic hemostasis to investigate whether oral esomeprazole at 40 mg twice daily following initial esomeprazole infusion reduced the incidence of recurrent PUB [35]. Evaluation at 14 days and the primary analysis at 28 days (10/93 [10.8%] vs. 27/94 [28.7%]; difference=-18%, -29% to -7%) presented improvements on further bleeding [35].

Currently, several PPIs with different features, pharmacokinetics, and clinical efficacies are available. One RCT comparing oral omeprazole and intravenous pantoprazole following endoscopic therapy in 106 patients with high-risk peptic ulcers did not demonstrate significant differences in the prevention of risk of rebleeding after endoscopic therapy (5/44 [11.4%] vs. 4/41 [9.8%], p=0.810) [28].

Long-term prevention

Regarding the long-term prevention of recurrent bleeding ulcers, patients with H. pylori-associated bleeding ulcers should undergo H. pylori eradication treatment [16]. According to a meta-analysis comparing the efficacy of eradication therapy versus antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer, it was concluded that H. pylori eradication therapy for the prevention of recurrent ulcer bleeding is significantly more effective than short-term antisecretory therapy alone [36]. Specifically, mean percentage of rebleeding in the eradication versus non-eradication therapy group presented result of 4.5% versus 23.7%; OR=0.18, 0.10–0.35 [36]. Furthermore, a comparison of the rebleeding rate between H. pylori eradication therapy group and long-term maintenance of non-eradication therapy group was 1.6% versus 5.6%; OR=0.24, 0.09–0.67 [36]. The rebleeding rate reached only 1% among patients with confined successful H. pylori eradication [36].

For patients with NSAID-associated bleeding ulcers, resuming NSAIDs should be carefully considered [16]. In patients who are not able to discontinue NSAIDs, a COX-2-selective NSAID at the lowest effective dose with daily PPI is recommended. According to a prospective randomized double-blind trial with 441 patients taking non-selective NSAIDs, recurrent ulcer bleeding was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI, 4.1–13.7; p=0.0004).

For patients with low-dose aspirin-associated bleeding ulcers, daily long-term PPI therapy is required [16]. Several randomized trials involving low-dose aspirin users have shown improvements in treatment outcomes with PPIs and standard-dose H2 blockers for peptic ulcers. Yeomans et al. [37] reported that 20 mg esomeprazole once daily reduced the risk of peptic ulcers. After a treatment duration of 26 weeks, 27 patients (5.4%) in the placebo group developed peptic ulcers, whereas in the PPI treatment group, only eight patients (1.6%) developed peptic ulcers; life-table estimates were 6.2% and 1.8%, respectively (p=0.0007) [37].

Potassium-competitive acid blockers and mucoprotective agents

Potassium-competitive acid blockers (P-CAB) are proton-pump antagonists that competitively bind to the K+-binding portion of activated H⁺/K⁺-ATPase parietal cells and interfere with the H+ exchange process. As the action of P-CAB is reversible and competitive, it rapidly suppresses acid secretion and maintains long-term activity. P-CAB has an effect similar to that of PPI in peptic ulcer treatment; however, to our knowledge, current studies lack evidence supporting its application in PUB treatment.

A pilot RCT of 44 patients comparing oral vonoprazan with continuous high-dose intravenous infusion of PPI as post-endoscopic management reported no significant difference in rebleeding at 3, 7, 30 days (e.g., 18.2% vs. 11.1% at 7 days, p=1.000) [38].

However, a recent retrospective study comparing oral P-CAB administration with intravenous infusion PPI before emergency endoscopy for patients with non-variceal UGIB presented evidence supporting pre-endoscopic treatment with oral PCAB tegoprazan was more effective than intravenous infusion of PPI and may have reduced mortality from ulcer bleeding [39]. The P-CAB treatment group had significantly fewer high-risk stigmata lesions (Forrest IIA or higher) and required fewer therapeutic endoscopic interventions (OR=0.272; p=0.004), and the rebleeding rate was significantly higher in the PPI group (OR=0.141; p=0.032) [39].

Another recent study outcome with P-CAB comparing the efficacy of vonoprazan and PPI for preventing high-risk peptic ulcer rebleeding after hemostasis demonstrated a result of noninferior 30-day rebleeding with P-CAB [40]. Specifically, in 194 patients, there was noninferiority (within a 10% margin) of vonoprazan compared to PPI (%risk difference, 3.3; 95% CI, 11.2–4.7; p<0.001) [40].

Mucoprotective agents, including misoprostol, rebamipide, and eupatilin, are useful for the prevention and improvement of UGIB clinical outcomes. Misoprostol is a synthetic prostaglandin E1 that effectively reduces gastric acid secretion and improves mucosal defense mechanisms. A significant reduction in NSAID-induced ulcer formation has been previously reported. Rostom et al. [41] reviewed 41 RCTs demonstrating the superiority of 800 μg/day misoprostol compared with 400 μg/day for the prevention of endoscopic gastric ulcers (RR=0.17 and RR=0.39, respectively; p=0.0055), including risk reduction for clinical ulcer complications. Furthermore, a 55% to 74% reduction was observed in the risk of peptic ulcer development by the combined administration of misoprostol with NSAIDs [41]. However, the presence of inevitable adverse events, including diarrhea, abdominal pain, and nausea, was a limitation of misoprostol treatment, which resulted in poor compliance [41].

Rebamipide is another mucoprotective agent that achieves a significant reduction in gastric bleeding risk among an Asian cohort of new users of NSAIDs (OR=0.65, 95% CI 0.44–0.96). Also, a multicenter RCT comparing rebamipide and misoprostol in long-term NSAID users demonstrated noninferiority of rebamipide for ulcer prevention [42].

Eupatilin has also shown promising results as a mucoprotective agent for the prevention of UGIB. Lee et al. [43] analyzed the data of 432 and 208 aspirin users from the Korean nationwide cohort database (NHIS) from 2013 to 2020. A significant improvement in UGIB prevention was observed following eupatilin administration combined with a PPI or H2RA (hazard ratio=0.85, p=0.016) compared with using only PPI or H2RA alone [43].

SUMMARY

The goal of the pharmacological treatment of PUB is to maintain gastric acidity above pH 6, suppress thrombolysis, and prevent rebleeding events. Table 1 summarizes the key factors in the current pharmacological management of ulcer bleeding. Currently, PPI is the primary initial management strategy. Pre-endoscopic therapy application with PPI may be considered, followed by high-dose PPI therapy for ≥3 days continuously or intermittently to achieve an improvement in further bleeding events and mortality. P-CAB is a superior strategy but lacks data on clinical outcomes, and future follow-up studies are required to provide further supporting evidence. Mucoprotective agents provide clinical evidence for the prevention and treatment of UGIB.

Table 1.

Summary of pharmacological management for patients with peptic ulcer bleeding

Notes

Authors’ Contribution

Conceptualization: Jun-Won Chung. Data curation: Jun-Won Chung, Hannah Lee. Investigation: all authors. Supervision: Jun-Won Chung. Writing—original draft: Jun-Won Chung, Hannah Lee. Writing—review & editing: all authors. Approval of final manuscript: all authors.

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Acknowledgements

None

References

1. Stanley AJ, Laine L. Management of acute upper gastrointestinal bleeding. BMJ 2019;364:l536.

2. Rockall TA, Logan RF, Devlin HB, Northfield TC, ; Steering Committee and Members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJ 1995;311:222–226.

3. Gilbert DA. Epidemiology of upper gastrointestinal bleeding. Gastrointest Endosc 1990;36(5 Suppl):S8–S13.

4. Longstreth GF. Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study. Am J Gastroenterol 1997;92:419–424.

5. Sung JJ, Chiu PW, Chan FKL, et al. Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018. Gut 2018;67:1757–1768.

6. Saydam ŞS, Molnar M, Vora P. The global epidemiology of upper and lower gastrointestinal bleeding in general population: a systematic review. World J Gastrointest Surg 2023;15:723–739.

7. Button LA, Roberts SE, Evans PA, et al. Hospitalized incidence and case fatality for upper gastrointestinal bleeding from 1999 to 2007: a record linkage study. Aliment Pharmacol Ther 2011;33:64–76.

8. Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol 2009;104:1633–1641.

9. Lau JY, Sung J, Hill C, Henderson C, Howden CW, Metz DC. Systematic review of the epidemiology of complicated peptic ulcer disease: incidence, recurrence, risk factors and mortality. Digestion 2011;84:102–113.

10. Sung JJ, Tsoi KK, Ma TK, Yung MY, Lau JY, Chiu PW. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases. Am J Gastroenterol 2010;105:84–89.

11. Ali Khan M, Howden CW. The role of proton pump inhibitors in the management of upper gastrointestinal disorders. Gastroenterol Hepatol (N Y) 2018;14:169–175.

12. Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978;74:38–43.

13. Low J, Dodds AJ, Biggs JC. Fibrinolytic activity of gastroduodenal secretions--a possible role in upper gastrointestinal haemorrhage. Thromb Res 1980;17:819–830.

14. Kolkman JJ, Meuwissen SG. A review on treatment of bleeding peptic ulcer: a collaborative task of gastroenterologist and surgeon. Scand J Gastroenterol Suppl 1996;218:16–25.

15. Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) guideline - update 2021. Endoscopy 2021;53:300–332.

16. Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG clinical guideline: upper gastrointestinal and ulcer bleeding. Am J Gastroenterol 2021;116:899–917.

17. Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007;356:1631–1640.

18. Sreedharan A, Martin J, Leontiadis GI, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev 2010;2010:CD005415.

19. Kanno T, Yuan Y, Tse F, Howden CW, Moayyedi P, Leontiadis GI. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev 2022;2022:CD005415.

20. Sung JJ, Barkun A, Kuipers EJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med 2009;150:455–464.

21. Lau JY, Sung JJ, Lee KK, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med 2000;343:310–316.

22. Javid G, Masoodi I, Zargar SA, et al. Omeprazole as adjuvant therapy to endoscopic combination injection sclerotherapy for treating bleeding peptic ulcer. Am J Med 2001;111:280–284.

23. Kaviani MJ, Hashemi MR, Kazemifar AR, et al. Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: a prospective, double-blind, randomized, clinical trial. Aliment Pharmacol Ther 2003;17:211–216.

24. Wei KL, Tung SY, Sheen CH, Chang TS, Lee IL, Wu CS. Effect of oral esomeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. J Gastroenterol Hepatol 2007;22:43–46.

25. Zargar SA, Javid G, Khan BA, et al. Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial. J Gastroenterol Hepatol 2006;21:716–721.

26. Hung WK, Li VK, Chung CK, et al. Randomized trial comparing pantoprazole infusion, bolus and no treatment on gastric pH and recurrent bleeding in peptic ulcers. ANZ J Surg 2007;77:677–681.

27. Jensen DM, Pace SC, Soffer E, Comer GM; 315 Study Group. Continuous infusion of pantoprazole versus ranitidine for prevention of ulcer rebleeding: a U.S. multicenter randomized, double-blind study. Am J Gastroenterol 2006;101:1991–1999. ; quiz 2170.

28. Mostaghni AA, Hashemi SA, Heydari ST. Comparison of oral and intravenous proton pump inhibitor on patients with high risk bleeding peptic ulcers: a prospective, randomized, controlled clinical trial. Iran Red Crescent Med J 2011;13:458–463.

29. Këlliçi I, Kraja B, Mone I, Prifti S. Role of intravenous omeprazole on non-variceal upper gastrointestinal bleeding after endoscopic treatment: a comparative study. Med Arh 2010;64:324–327.

30. van Rensburg C, Barkun AN, Racz I, et al. Clinical trial: intravenous pantoprazole vs. ranitidine for the prevention of peptic ulcer rebleeding: a multicentre, multinational, randomized trial. Aliment Pharmacol Ther 2009;29:497–507.

31. Lin HJ, Lo WC, Lee FY, Perng CL, Tseng GY. A prospective randomized comparative trial showing that omeprazole prevents rebleeding in patients with bleeding peptic ulcer after successful endoscopic therapy. Arch Intern Med 1998;158:54–58.

32. Gashi Z, Joksimovic N, Dragusha G, Bakalli A. The efficacy of PPI after endoscopic hemostasis in patients with bleeding peptic ulcer and role of Helicobacter pylori. Med Arch 2012;66:236–239.

33. Demetrashvili ZM, Lashkhi IM, Ekaladze EN, Kamkamidze GK. Comparison of intravenous pantoprazole with intravenous ranitidine in peptic ulcer bleeding. Georgian Med News 2013;(223):7–11.

34. Villanueva C, Balanzó J, Torras X, et al. Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study. Endoscopy 1995;27:308–312.

35. Cheng HC, Wu CT, Chang WL, Cheng WC, Chen WY, Sheu BS. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut 2014;63:1864–1872.

36. Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Muñoz E. Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. Aliment Pharmacol Ther 2004;19:617–629.

37. Yeomans N, Lanas A, Labenz J, et al. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol 2008;103:2465–2473.

38. Pattarapuntakul T, Wong T, Wetwittayakhlang P, et al. Efficacy of vonoprazan vs. intravenous proton pump inhibitor in prevention of re-bleeding of high-risk peptic ulcers: a randomized controlled pilot study. J Clin Med 2024;13:3606.

39. Lim NR, Chung WC. Intravenous proton pump inhibitors vs oral potassium competitive acid blockers before endoscopic treatment of bleeding peptic ulcers. World J Gastrointest Endosc 2025;17:104234.

40. Geeratragool T, Kaosombatwattana U, Boonchote A, et al. Comparison of vonoprazan versus intravenous proton pump inhibitor for prevention of high-risk peptic ulcers rebleeding after successful endoscopic hemostasis: a multicenter randomized noninferiority trial. Gastroenterology 2024;167:778–787. e3.

41. Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002;2002:CD002296.

42. Park SH, Cho CS, Lee OY, et al. Comparison of prevention of NSAID-induced gastrointestinal complications by rebamipide and misoprostol: a randomized, multicenter, controlled trial-STORM STUDY. J Clin Biochem Nutr 2007;40:148–155.

43. Lee HS, Nam JH, Oh DJ, Moon YR, Lim YJ. Reduced risk of gastrointestinal bleeding associated with eupatilin in aspirin plus acid suppressant users: nationwide population-based study. Korean J Intern Med 2024;39:261–271.

Article information Continued

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.