PPI versus H2RA for Both the Prevention of Bleeding and the Healing of Ulcer after ESD: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

ZHANG Jixiang ,  DONG Weiguo , YANG Zirong , QIU Shi , AI Minghua , WANG Jing

People’s Hospital of Wuhan University, Wuhan 430060, China;

Corresponding author：

DONG Weiguo, Email: dwg@edu.whu.cn

Keywords：

Proton pump inhibitor; H2 receptor antagonist; Endoscopic submucosal dissection; Ulcer; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20120231

Video：

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Objective 　To compare proton pump inhibitors (PPI) and H2 receptor antagonists (H2RA) for both the prevention of bleeding and the healing of ulcer after endoscopic submucosal dissection (ESD), so as to provide best evidence for treating ESD-induced ulcer in clinic.
Methods 　Databases including PubMed, CENTRAL, EMbase, ISI Web of Knowledge, VIP, CNKI, CBM and WanFang Data were searched from the date of their establishment to October 26, 2012 to collect the randomized controlled trials (RCTs) about comparison of PPI and H2RA on the prevention of bleeding and the healing of ulcer after ESD. Meanwhile the references of the included studies were also retrieved manually. According to the inclusion and exclusion criteria, literature selection, data extraction and quality assessment were performed by four reviewers independently, and meta-analysis was performed using RevMan 5.1 software.
Results 　A total of 6 studies involving 616 patients were included finally. The results of meta-analysis showed that: for the prevention of ulcer bleeding after ESD, PPI preceded H2RA apparently (OR=0.51, 95%CI 0.29 to 0.89, P=0.02), especially when the treatment course was 8-week (OR=0.43, 95%CI 0.22 to 0.82, P=0.01); but among the merged, 8-week and 4-week groups, there were no significant differences between PPI and H2RA in the healing of ESD-induced ulcer (OR=0.85, 95%CI 0.39 to 1.86, P=0.69; OR=1.33, 95%CI 0.28 to 6.27, P=0.72; OR=0.75, 95%CI 0.31 to 1.79, P=0.52).
Conclusion 　PPI is superior to H2RA for the prevention of ulcer bleeding induced by ESD, but there is no significant difference between them in the healing of ulcer, so PPI is recommended to prevent ESD-induced ulcer bleeding in clinic. Due to the limitation of quantity and quality of the included studies, the safety of PPI has to be further proved by conducting more high quality, large scale and multicenter RCTs.

Citation： ZHANG Jixiang,DONG Weiguo,YANG Zirong,QIU Shi,AI Minghua,WANG Jing. PPI versus H2RA for Both the Prevention of Bleeding and the Healing of Ulcer after ESD: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2012, 12(12): 1503-1509. doi: 10.7507/1672-2531.20120231 Copy

1.	Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut, 2001, 48(2): 225-229.
2.	Chung IK, Lee JH, Lee SH, et al. Therapeutic outcomes in 1000 cases of endoscopic submucosal dissection for early gastric neoplasms: Korean ESD Study Group multicenter study. Gastrointest Endosc, 2009, 69(7): 1228-1235.
3.	Watanabe K, Ogata S, Kawazoe S, et al. Clinical outcomes of EMR for gastric tumors: Historical pilot evaluation between endoscopic submucosal dissection and conventional mucosal resection. Gastrointest Endosc, 2006, 63(6): 776-782.
4.	Shin WG, Kim SJ, Choi MH, et al. Can rebamipide and proton pump inhibitor combination therapy promote the healing of endoscopic submucosal dissection-induced ulcers? A randomized, prospective, multicenter study. Gastrointest Endosc, 2012, 75(4): 739-747.
5.	Lee SY, Kim JJ, Lee JH, et al. Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole. Gastrointest Endosc, 2004, 60(2): 213-217.
6.	Oh TH, Jung HY, Choi KD, et al. Degree of healing and healing-associated factors of endoscopic submucosal dissection-induced ulcers after pantoprazole therapy for 4 weeks. Dig Dis Sci, 2009, 54(7): 1494-1499.
7.	Kim YG, Jang BI, Kim TN. A matched case-control study of a novel acid-pump antagonist and proton-pump inhibitor for the treatment of iatrogenic ulcers caused by endoscopic submucosal dissection. Gut Liver, 2010, 4(1): 25-30.
8.	Kato T, Araki H, Onogi F, et al. Clinical trial: rebamipide promotes gastric ulcer healing by proton pump inhibitor after endoscopic submucosal dissection—a randomized controlled study. J Gastroenterol, 2010, 45(3): 285-290.
9.	Jeong HK, Park CH, Jun CH, et al. A prospective randomized trial of either famotidine or pantoprazole for the prevention of bleeding after endoscopic submucosal dissection. J Korean Med Sci, 2007, 22: 1055-1059.
10.	Uedo N, Takeuchi Y, Yamada T, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol, 2007, 102(8): 1610-1616.
11.	Ohya TR, Endo H, Kawagoe K, et al. A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers. World J Gastrointest Endosc, 2010, 2(1): 36-40.
12.	Imaeda H, Hosoe N, Suzuki H, et al. Effect of lansoprazole versus roxatidine on prevention of bleeding and promotion of ulcer healing after endoscopic submucosal dissection for superficial gastric neoplasia. J Gastroenterol, 2011, 46(11): 1267-1272.
13.	Takeuchi N, Umegaki E, Takeuchi T, et al. Half-Dose Rabeprazole Has an Equal Efficacy to Standard-Dose Rabeprazole on Endoscopic Submucosal Dissection-Induced Ulcer. J Clin Biochem Nutr, 2011, 49(3): 216–221.
14.	Tomita T, Kim Y, Yamasaki T, et al. A prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection. J Gastroenterol Hepatol, 2012, doi: 10.1111/j.1440-1746.
15.	Bañares R, Albillos A, Rincón D, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology, 2002, 35(3): 609-615.
16.	Oh JH, Choi MG, Dong MS, et al. Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients. J Gastroenterol Hepatol, 2007, 22(9): 1429-1434.
17.	Ono S, Kato M, Ono Y, et al. Effects of preoperative administration of omeprazole on bleeding after endoscopic submucosal dissection: a prospective randomized controlled trial. Endoscopy, 2009, 41(4): 299-303.
18.	Green FW Jr, Kaplan MM, Curtis LE, et al. Effect of acid and pepsin on blood coagulation and platelet aggregation. Gastroenterology, 1978, 74(1): 38-43.
19.	Lee SY, Kim JJ, Lee JH, et al. Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole. Gastrointest Endosc, 2004, 60(2): 213–217.
20.	Villanueva C, Blanzo J, Sainz S, et al. Omeprazole versus ranitidine as adjuct therapy to endoscopic injection in actively bleeding ulcer: a prospective and randomized study. Endoscopy, 1995, 27(4): 308-312.
21.	Yacyshyn BR, Thomason ABR. Critical review of acid suppression in nonvariceal, acute, upper gastrointestinal bleeding. Dig Dis, 2000, 18(3): 117-128.
22.	Stedman CA, Barclay ML. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther, 2000, 14(8): 963-978.
23.	Soetikno RM, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection. Gastrointest Endosc, 2003, 57(4): 567-579.
24.	Lin HJ, Lo WC, Lee FY, et al. 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(1): 54-58.
25.	Lau JY, Sung JJ, Lee KK, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding ulcers. N Engl J Med, 2000, 343(5): 310-316.

1. Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of early gastric cancer. Gut, 2001, 48(2): 225-229.
2. Chung IK, Lee JH, Lee SH, et al. Therapeutic outcomes in 1000 cases of endoscopic submucosal dissection for early gastric neoplasms: Korean ESD Study Group multicenter study. Gastrointest Endosc, 2009, 69(7): 1228-1235.
3. Watanabe K, Ogata S, Kawazoe S, et al. Clinical outcomes of EMR for gastric tumors: Historical pilot evaluation between endoscopic submucosal dissection and conventional mucosal resection. Gastrointest Endosc, 2006, 63(6): 776-782.
4. Shin WG, Kim SJ, Choi MH, et al. Can rebamipide and proton pump inhibitor combination therapy promote the healing of endoscopic submucosal dissection-induced ulcers? A randomized, prospective, multicenter study. Gastrointest Endosc, 2012, 75(4): 739-747.
5. Lee SY, Kim JJ, Lee JH, et al. Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole. Gastrointest Endosc, 2004, 60(2): 213-217.
6. Oh TH, Jung HY, Choi KD, et al. Degree of healing and healing-associated factors of endoscopic submucosal dissection-induced ulcers after pantoprazole therapy for 4 weeks. Dig Dis Sci, 2009, 54(7): 1494-1499.
7. Kim YG, Jang BI, Kim TN. A matched case-control study of a novel acid-pump antagonist and proton-pump inhibitor for the treatment of iatrogenic ulcers caused by endoscopic submucosal dissection. Gut Liver, 2010, 4(1): 25-30.
8. Kato T, Araki H, Onogi F, et al. Clinical trial: rebamipide promotes gastric ulcer healing by proton pump inhibitor after endoscopic submucosal dissection—a randomized controlled study. J Gastroenterol, 2010, 45(3): 285-290.
9. Jeong HK, Park CH, Jun CH, et al. A prospective randomized trial of either famotidine or pantoprazole for the prevention of bleeding after endoscopic submucosal dissection. J Korean Med Sci, 2007, 22: 1055-1059.
10. Uedo N, Takeuchi Y, Yamada T, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol, 2007, 102(8): 1610-1616.
11. Ohya TR, Endo H, Kawagoe K, et al. A prospective randomized trial of lafutidine vs rabeprazole on post-ESD gastric ulcers. World J Gastrointest Endosc, 2010, 2(1): 36-40.
12. Imaeda H, Hosoe N, Suzuki H, et al. Effect of lansoprazole versus roxatidine on prevention of bleeding and promotion of ulcer healing after endoscopic submucosal dissection for superficial gastric neoplasia. J Gastroenterol, 2011, 46(11): 1267-1272.
13. Takeuchi N, Umegaki E, Takeuchi T, et al. Half-Dose Rabeprazole Has an Equal Efficacy to Standard-Dose Rabeprazole on Endoscopic Submucosal Dissection-Induced Ulcer. J Clin Biochem Nutr, 2011, 49(3): 216–221.
14. Tomita T, Kim Y, Yamasaki T, et al. A prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection. J Gastroenterol Hepatol, 2012, doi: 10.1111/j.1440-1746.
15. Bañares R, Albillos A, Rincón D, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology, 2002, 35(3): 609-615.
16. Oh JH, Choi MG, Dong MS, et al. Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients. J Gastroenterol Hepatol, 2007, 22(9): 1429-1434.
17. Ono S, Kato M, Ono Y, et al. Effects of preoperative administration of omeprazole on bleeding after endoscopic submucosal dissection: a prospective randomized controlled trial. Endoscopy, 2009, 41(4): 299-303.
18. Green FW Jr, Kaplan MM, Curtis LE, et al. Effect of acid and pepsin on blood coagulation and platelet aggregation. Gastroenterology, 1978, 74(1): 38-43.
19. Lee SY, Kim JJ, Lee JH, et al. Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole. Gastrointest Endosc, 2004, 60(2): 213–217.
20. Villanueva C, Blanzo J, Sainz S, et al. Omeprazole versus ranitidine as adjuct therapy to endoscopic injection in actively bleeding ulcer: a prospective and randomized study. Endoscopy, 1995, 27(4): 308-312.
21. Yacyshyn BR, Thomason ABR. Critical review of acid suppression in nonvariceal, acute, upper gastrointestinal bleeding. Dig Dis, 2000, 18(3): 117-128.
22. Stedman CA, Barclay ML. Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther, 2000, 14(8): 963-978.
23. Soetikno RM, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection. Gastrointest Endosc, 2003, 57(4): 567-579.
24. Lin HJ, Lo WC, Lee FY, et al. 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(1): 54-58.
25. Lau JY, Sung JJ, Lee KK, et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding ulcers. N Engl J Med, 2000, 343(5): 310-316.

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PPI versus H2RA for Both the Prevention of Bleeding and the Healing of Ulcer after ESD: A Meta-Analysis

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