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Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial

  • Original Article—Alimentary Tract
  • Published:
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Abstract

Background

Patients using low-dose aspirin (LDA) have an increased risk of gastroduodenal mucosal lesions and upper gastrointestinal symptoms. We aimed to clarify the efficacy of rabeprazole for preventing peptic ulcer, esophagitis, and gastrointestinal symptoms associated with LDA.

Methods

Patients with a history of peptic ulcers who were receiving LDA for cardiovascular or cerebrovascular disease were randomly assigned to receive rabeprazole at 10 mg daily, rabeprazole at 20 mg daily, or gefarnate (a cytoprotective anti-ulcer agent) at 50 mg twice daily. The primary endpoint was the development of gastric and/or duodenal ulcer at 12 weeks. The modified Lanza score (MLS) and gastrointestinal symptoms were evaluated at baseline and at 12 weeks.

Results

The full analysis set comprised 261 patients (rabeprazole 10 mg: n = 87, rabeprazole 20 mg: n = 89, gefarnate 100 mg: n = 85). The cumulative incidences of gastroduodenal ulcers at 12 weeks in the 10 mg rabeprazole group, 20 mg rabeprazole group, and gefarnate group were 7.4, 3.7, and 26.7 %, respectively (rabeprazole group 5.5 % vs. gefarnate group 26.7 %, hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.082–0.394; p < 0.0001). The proportions of patients with an MLS of ≥1 and erosive esophagitis were significantly lower in the rabeprazole group than in the gefarnate group at 12 weeks (gastric lesions 33.5 vs. 62.4 %, p < 0.0001; duodenal lesions 5.7 vs. 24.7 %, p < 0.0001; erosive esophagitis 5.8 vs. 19.4 %, p < 0.0001). Rabeprazole was significantly more effective than gefarnate for the resolution and prevention of gastrointestinal symptoms (resolution 53.6 vs. 25.0 %, p = 0.017; occurrence 9.2 vs. 28.3 %, p = 0.0026).

Conclusions

Rabeprazole is more effective than gefarnate for reducing the risk of recurrence of peptic ulcer, esophagitis, and gastrointestinal symptoms in LDA users.

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Acknowledgments

This study was funded by a grant provided by the NPO-Corporation, Gastrointestinal Medical Care Research and Education Center. We are very grateful to Mr. Tagaji Ikami and Miss Yuko Osawa for their dedicated secretarial assistance. We also thank Mr. Koichi Yamashiro, Ms. Kyoko Murata, Ms. Kikuko Oshima, and Ms. Tomomi Sakabayashi for their assistance with the web system and statistical analysis. We thank Mr. Hiroshi Furuichi for his assistance in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Tsuyoshi Sanuki, Tsuyoshi Fujita, Hiromu Kutsumi, Takanobu Hayakumo, Manabu Murakami & Takeshi Azuma

  2. Tabata Gastrointestinal Hospital, 111-1 Morita, Okubo-cho, Akashi, 674-0061, Japan

    Shun-ichi Yoshida

  3. Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi, 673-8558, Japan

    Hideto Inokuchi

  4. Department of Data Management and Analyses, Translational Research Informatics Center, 1-5-4 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Yoshihiro Matsubara

  5. Center for Bioethics and Humanities, State University of New York, 618 Irving Avenue, Room 102, Syracuse, NY, 13210, USA

    Hajime Kuwayama

  6. Department of Gastroenterology, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya, 343-8555, Japan

    Hajime Kuwayama

  7. Endoscopy Center, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Takashi Kawai

  8. Miyaji Medical Clinic, 2-9-3 Kagetsu, Fukui, 910-0022, Japan

    Hideki Miyaji

  9. Department of Gastroenterology, Kakogawa West City Hospital, 384-1 Hiratsu, Yoneda-cho, Kakogawa, 675-8611, Japan

    Takashi Fujisawa

  10. Department of Gastroenterology, Kakogawa East City Hospital, 797-295 Isshiki, Hiraoka-cho, Kakogawa, 675-0115, Japan

    Shuichi Terao

  11. Department of Endoscopic Medicine, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan

    Yukinao Yamazaki

Authors
  1. Tsuyoshi Sanuki
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  2. Tsuyoshi Fujita
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  15. Takeshi Azuma
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Consortia

Care Study Group

Corresponding author

Correspondence to Takeshi Azuma.

Additional information

The members of the Care Study Group are listed in the "Appendix".

Appendix

Appendix

The Care Study Group consists of Akira Yamashina, Tokyo Medical University Hospital, Shinjuku, Tokyo; Takahisa Furuta, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka; Manabu Dojo, Fukui Red Cross Hospital, Fukui, Fukui; Tomoko Inagaki, Fukui Hospital Social Insurance, Katsuyama, Fukui; Shigeji Ito, Tannan Regional Medical Center, Sabae, Fukui; Takuo Kado, Nakamura Hospital, Echizen, Fukui; Yoshie Otaki, Otaki Hospital, Fukui, Fukui; Masamichi Hirai, Hirai Primary Care Clinic, Echizen, Fukui; Yusuke Okuyama, Kyoto First Red Cross Hospital, Kyoto, Kyoto; Yoshinobu Matsumori, Aijinkai Takatsuki Hospital Medical Corporation, Takatsuki, Osaka; Kiyoshi Ashida, Osaka Saiseikai Nakatsu Hospital, Osaka, Osaka; Seiji Shimizu, Osaka Railway Hospital, Osaka, Osaka; Kyota Ohno, Chibune General Hospital, Osaka, Osaka; Akira Nakamura, Sanda City Hospital, Sanda, Hyogo; Hiroshi Yoshida, Yoshida Ardent Hospital, Kobe, Hyogo; Hiroyuki Yamada, Rokko Island Hospital, Kobe, Hyogo; Ryo Chinzei, Ken-ichi Hirata, and Midori Hirai, Kobe University Hospital, Kobe, Hyogo; Tetsuro Inokuma, Kobe City Medical Center General Hospital, Kobe, Hyogo; Takao Shimada, Kobe Century Memorial Hospital, Kobe, Hyogo; Takatoshi Nakashima, Akashi Medical Center, Akashi, Hyogo; Seiichi Hirano, Miki City Hospital, Miki, Hyogo; Sachiko Ouchi, Steel Memorial Hirohata Hospital, Himeji, Hyogo; Isao Utaka, Kakogawa East City Hospital, Kakogawa, Hyogo; Takumi Takauchi, Yoka Hospital, Yabu, Hyogo; Akihiko Taira, Tsuyama Chuo Hospital, Tsuyama, Okayama; Koji Takeuchi, Kyoto Pharmaceutical University, Kyoto, Kyoto; Yoshiyuki Watanabe, Kyoto Prefectural University of Medicine, Kyoto, Kyoto; and Shigeto Mizuno, Kobe Pharmaceutical University, Kobe, Hyogo.

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Sanuki, T., Fujita, T., Kutsumi, H. et al. Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial. J Gastroenterol 47, 1186–1197 (2012). https://doi.org/10.1007/s00535-012-0588-x

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  • DOI: https://doi.org/10.1007/s00535-012-0588-x

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