pp 1–5 | Cite as

Risk of hemorrhage and stricture significantly increases in elderly patients with proton pump inhibitor (PPI)-resistant reflux esophagitis

  • Nana Takenouchi
  • Shintaro Hoshino
  • Yoshimasa Hoshikawa
  • Tomohide Tanabe
  • Mai Koeda
  • Eri Momma
  • Yumiko Ishikawa
  • Noriyuki Kawami
  • Mitsuru Kaise
  • Katsuhiko IwakiriEmail author
Original Article



To examine the clinical characteristics, including complications, of patients older than 75 years of age with proton pump inhibitor-resistant reflux esophagitis.


Patients who were resistant to standard-dose proton pump inhibitors were enrolled in the present study. Eligible patients (n = 26) were divided into those who were older (n = 11) and younger (n = 15) than 75 years of age. Clinical characteristics including complications (hemorrhage and stricture), body mass index, the severity of reflux esophagitis, Helicobactor pylori infection, gastric mucosal atrophy, hiatal hernia, kyphosis, and the use of antithrombotic agents were examined. The efficacy of 20 mg vonoprazan for proton pump inhibitor-resistant reflux esophagitis was also investigated.


The severity of reflux esophagitis was significantly higher in the elderly group than in the non-elderly group. No other significant differences were observed between the groups. The proportion of patients with hemorrhage was significantly larger in the elderly group than in the non-elderly group. Similarly, the proportion of patients with stricture was significantly larger in the elderly group than in the non-elderly group. Nine out of 10 patients in the elderly group and all patients in the non-elderly group achieved healing after the 4-week administration of 20 mg vonoprazan. No significant differences were observed in healing rates between the groups.


Among patients with proton pump inhibitor-resistant reflux esophagitis, the rates of severe reflux esophagitis and complications (hemorrhage and/or stricture) were significantly higher in elderly patients than in non-elderly patients. Regardless of age, 20 mg vonoprazan was effective for proton pump inhibitor-resistant reflux esophagitis.


PPI-resistant reflux esophagitis Complication Stricture Bleeding Vonoprazan 



The authors thank Ms. Satoko Nishimura for her administrative assistance.

Compliance with ethical standards

Ethical Statement

All procedures followed were in accordance with the approval of the Ethics Committee of Nippon Medical School Hospital and the guidelines set forth in the Declaration of Helsinki revised in 2000. Informed consent was obtained from all subjects included in the study.

Conflict of interest

Katsuhiko Iwakiri has received lecture fees from Takeda Pharmaceutical Co., Ltd. and Otsuka Pharmaceutical Co., Ltd.. The remaining authors declare that they have no conflicts of interest.


  1. 1.
    Haruma K, Kamada T, Kawaguchi H, et al. Effect of age and Helicobacter pylori infection on gastric acid secretion. J Gastroenterol Hepatol. 2000;15:277–83.CrossRefGoogle Scholar
  2. 2.
    Lee J, Anggiansah A, Anggiansah R, et al. Effects of age on the gastroesophageal junction, esophageal motility, and reflux disease. Clin Gastroenterol Hepatol. 2007;5:1392–8.CrossRefGoogle Scholar
  3. 3.
    Kawami N, Iwakiri K, Sano H, et al. Effects of aging and acid reflux on esophageal motility. Digestion. 2015;91:181–6.CrossRefGoogle Scholar
  4. 4.
    Iwakiri K, Kinoshita Y, Habu Y, et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015. J Gastroenterol. 2016;51:751–67.CrossRefGoogle Scholar
  5. 5.
    Fujimoto K, Hongo M. Risk factors for relapse of erosive GERD during long-term maintenance treatment with proton pump inhibitor: a prospective multicenter study in Japan. J Gastroenterol. 2010;45:1193–200.CrossRefGoogle Scholar
  6. 6.
    Furuta T, Shimatani T, Sugimoto M, et al. Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant patients with gastroesophageal reflux disease and the dose escalation challenge of PPIs-TORNADO study: a multicenter prospective study by the Acid-Related Symptom Research Group in Japan. J Gastroenterol. 2011;46:1273–83.CrossRefGoogle Scholar
  7. 7.
    Watanabe A, Iwakiri R, Yamaguchi D, et al. Risk factors for resistance to proton pump inhibitor maintenance therapy for reflux esophagitis in Japanese women over 60 years. Digestion. 2012;86:323–8.CrossRefGoogle Scholar
  8. 8.
    Mizuno H, Matsuhashi N, Sakaguchi M, et al. Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan. J Clin Biochem Nutr. 2015;57:233–8.CrossRefGoogle Scholar
  9. 9.
    Jenkins H, Sakurai Y, Nishimura A, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015;41:636–48.CrossRefGoogle Scholar
  10. 10.
    Sakurai Y, Mori Y, Okamoto H, et al. Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects–a randomised open-label cross-over study. Aliment Pharmacol Ther. 2015;42:719–30.CrossRefGoogle Scholar
  11. 11.
    Ashida K, Sakurai Y, Nishimura A, et al. Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis. Aliment Pharmacol Ther. 2015;42:685–95.CrossRefGoogle Scholar
  12. 12.
    Pisegna J, Holtmann G, Howden CW, et al. Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2004;20(Suppl 9):47–56.CrossRefGoogle Scholar
  13. 13.
    Belhocine K, Galmiche JP. Epidemiology of the complications of gastroesophageal reflux disease. Dig Dis. 2009;27:7–13.CrossRefGoogle Scholar
  14. 14.
    Sakaguchi M, Manabe N, Ueki N, et al. Factors associated with complicated erosive esophagitis: A Japanese multicenter, prospective, cross-sectional study. World J Gastroenterol. 2017;23:318–27.CrossRefGoogle Scholar
  15. 15.
    Kawami N, Takenouchi N, Umezawa M, et al. Pathogenesis of double-dose proton pump inhibitor-resistant non-erosive reflux disease, and mechanism of reflux symptoms and gastric acid secretion-suppressive effect in the presence or absence of helicobacter pylori infection. Digestion. 2017;95:140–5.CrossRefGoogle Scholar
  16. 16.
    Sugiura T, Iwakiri K, Kotoyori M, et al. Relationship between severity of reflux esophagitis according to the Los Angeles classification and esophageal motility. J Gastroenterol. 2001;36:226–30.CrossRefGoogle Scholar
  17. 17.
    Iwakiri K, Hoshino S, Kawami N. Mechanisms underlying excessive esophageal acid exposure in patients with gastroesophageal reflux disease. Esophagus. 2017;14:221–8.CrossRefGoogle Scholar
  18. 18.
    Iwakiri K. Treatment strategy for standard dose proton pump inhibitor-resistant reflux esophagitis. J Nippon Med Sch. 2017;84:209–14.CrossRefGoogle Scholar
  19. 19.
    Jenkins H, SakuraiY Nishimura A, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015;41:636–48.CrossRefGoogle Scholar
  20. 20.
    Bell NJ, Burget D, Howden CW, et al. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion. 1992;51(Suppl 1):59–67.CrossRefGoogle Scholar
  21. 21.
    Hoshino S, Kawami N, Takenouchi N, et al. Efficacy of vonoprazan for proton pump inhibitor-resistant reflux esophagitis. Digestion. 2017;95:156–61.CrossRefGoogle Scholar
  22. 22.
    Tanabe T, Hoshino S, Kawami N, et al. Efficacy of long term maintenance therapy with 10-mg vonoprazan for proton-pump inhibitor-resistant reflux esophagitis. Esophagus. 2019;16:377–81.CrossRefGoogle Scholar
  23. 23.
    Yamasaki H, Kawaguchi N, Nonaka M, et al. In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2016;14:1–8.Google Scholar
  24. 24.
    Furuta T, Shirai N, Watanabe F, et al. Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther. 2002;72:453–60.CrossRefGoogle Scholar

Copyright information

© The Japan Esophageal Society 2019

Authors and Affiliations

  • Nana Takenouchi
    • 1
  • Shintaro Hoshino
    • 1
  • Yoshimasa Hoshikawa
    • 1
  • Tomohide Tanabe
    • 1
  • Mai Koeda
    • 1
  • Eri Momma
    • 1
  • Yumiko Ishikawa
    • 1
  • Noriyuki Kawami
    • 1
  • Mitsuru Kaise
    • 1
  • Katsuhiko Iwakiri
    • 1
    Email author
  1. 1.Department of Gastroenterology, Nippon Medical SchoolGraduate School of MedicineBunkyo-kuJapan

Personalised recommendations