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Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

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Abstract

Purpose

We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT).

Methods

This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure.

Results

The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan–Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82–1.86)]; there were no significant differences in secondary endpoints.

Conclusion

Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT.

Trial Registration

Clinicaltrials.gov number: NCT00212017

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Acknowledgements

We thank Satomi Ihara for her excellent assistance with the data management and Yuri Takagaki, Chizuru Takayama, Yuka Miyawaki, and Kuniko Shishikura for the data monitoring.

Author information

Author notes

  1. Hiroshi Asanuma

    Present address: Cardiovascular Science and Technology, Kyoto Prefectural University of Medicine, Kyoto, Japan

  2. Toshimitsu Hamasaki

    Present address: Department of Data Science, National Cerebral and Cardiovascular Center, Osaka, Japan

  3. Tohru Kohno

    Present address: Department of Cardiology, Kasukabe Municipal Hospital, Saitama, Japan

  4. Tatsuya Nunohiro

    Present address: Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan

Authors and Affiliations

  1. Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center Suita, Osaka, 565-8565, Japan

    Masanori Asakura, Jiyoong Kim & Masafumi Kitakaze

  2. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan

    Masanori Asakura & Masafumi Kitakaze

  3. Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan

    Hiroshi Asanuma

  4. Department of Biomedical Statistics, Osaka University Graduate School of Medicine, Suita, Japan

    Toshimitsu Hamasaki

  5. Division of Cardiology, Yokohama City University Medical Center, Kanagawa, Japan

    Kengo Tsukahara

  6. Department of Cardiology, Higashi Takarazuka Satoh Hospital, Hyogo, Japan

    Yorihiko Higashino

  7. Department of Cardiology, Saitama Prefecture Cardiovascular and Respiratory Center, Saitama, Japan

    Tetsuya Ishikawa

  8. Department of Cardiology, Hiroshima City Hospital, Hiroshima, Japan

    Yasuharu Nakama

  9. Division of Cardiology, Department of Medicine, Showa University Hospital, Tokyo, Japan

    Shinji Koba

  10. Department of Cardiology, Iwatsuki-minami Hospital, Saitama, Japan

    Yasuyuki Maruyama

  11. Department of Cardiology, Cardiovascular Center, Veritas Hospital, Hyogo, Japan

    Mitsuru Tsujimoto

  12. Division of Cardiology, Fujisawa City Hospital, Kanagawa, Japan

    Hideo Himeno

  13. Department of Cardiology, Hokko Memorial Hospital, Hokkaido, Japan

    Takanori Ohkusa

  14. Department of Cardiology, Fukui Prefectural Hospital, Fukui, Japan

    Susumu Fujino

  15. Department of Cardiology, International Goodwill Hospital, Kanagawa, Japan

    Makoto Shimizu

  16. Department of Cardiology, Saiseikai Yokohama City Southern Hospital, Kanagawa, Japan

    Tsutomu Endo

  17. Division of Cardiology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

    Shunichi Yoda

  18. Department of Cardiology, National Hospital Organization Ureshino Medical Center, Saga, Japan

    Takahiro Muroya

  19. Department of Cardiology, Nagoya University Graduate School of Medicine, Aichi, Japan

    Toyoaki Murohara

  20. Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan

    Nobuyuki Ohte

  21. Division of Cardiology, Showa University Fujigaoka Hospital, Kanagawa, Japan

    Hiroshi Suzuki

  22. Department of Cardiology, Tokyo Rinkai Hospital, Tokyo, Japan

    Tohru Kohno

  23. Division of Cardiology, Kanagawa Cardiovascular Respiratory Center, Kanagawa, Japan

    Kazuki Fukui

  24. Department of Cardiology, Kitasato University Medical Center, Saitama, Japan

    Takaaki Shiono

  25. Department of Internal Medicine, Enshu Hospital, Shizuoka, Japan

    Hiroyuki Takase

  26. Department of Cardiology, Fukui University Hospital, Fukui, Japan

    Hiroyasu Uzui

  27. Department of Cardiology, Rinku General Medical Center, Osaka, Japan

    Yoshiyuki Nagai

  28. Department of Cardiology, Kameda Medical Center, Chiba, Japan

    Yuji Hashimoto

  29. Division of Cardiology, Uwajima City Hospital, Ehime, Japan

    Shuntaro Ikeda

  30. Department of Cardiology, Fukui Cardiovascular Center, Fukui, Japan

    Sumio Mizuno

  31. Department of Cardiology, Nishinomiya Watanabe Cardiovascular Center, Hyogo, Japan

    Koichi Tamita

  32. Department of Cardiovascular Division, Kansai Rosai Hospital, Hyogo, Japan

    Masashi Fujita

  33. Department of Cardiology, Fukui General Clinic, Fukui, Japan

    Kazuo Satake

  34. Kinoshita Clinic, Hiroshima, Japan

    Yoshihiko Kinoshita

  35. Department of Cardiology, Nagasaki Municipal Hospital, Nagasaki, Japan

    Tatsuya Nunohiro

  36. Department of Cardiology, National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan

    Satoru Sakagami

  37. Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Ehime, Japan

    Jitsuo Higaki

  38. Department of Cardiology, Hokusetsu General Hospital, Osaka, Japan

    Isao Morii

  39. Department of Cardiology, Hadano Red Cross Hospital, Kanagawa, Japan

    Reimin Sawada

  40. Department of Cardiology, Tokushima Red Cross Hospital, Tokushima, Japan

    Yoshikazu Hiasa

  41. Department of Cardiovascular Medicine, International University of Health and Welfare Atami Hospital, Shizuoka, Japan

    Tomohiko Shigemasa

  42. Department of Cardiology, Fukuyama City Hospital, Hiroshima, Japan

    Makoto Nakahama

  43. Department of Cardiovascular Medicine, University of Tokushima, Tokushima, Japan

    Masataka Sata

  44. Department of Cardiology, Shizuoka Prefectural General Hospital, Shizuoka, Japan

    Osamu Doi

  45. Department of Cardiology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan

    Tetsuro Ueda

  46. Division of Cardiology, Osaka General Medical Center, Osaka, Japan

    Takahisa Yamada

  47. Department of Cardiology, Department of Internal Medicine, Hitachi, Ltd. Hitachinaka General Hospital, Ibaraki, Japan

    Takayoshi Yamanouchi

  48. Yamaguchi Clinic, Fukushima, Japan

    Hajime Yamaguchi

  49. Department of Cardiology, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan

    Yukiko Morita

  50. Department of Internal Medicine, Hoetsu Hospital, Tokurshima, Japan

    Hideki Hayashi

Authors
  1. Masanori Asakura
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  2. Jiyoong Kim
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  3. Hiroshi Asanuma
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  4. Toshimitsu Hamasaki
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  5. Kengo Tsukahara
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  6. Yorihiko Higashino
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  7. Tetsuya Ishikawa
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  8. Yasuharu Nakama
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  9. Shinji Koba
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  10. Yasuyuki Maruyama
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  11. Mitsuru Tsujimoto
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  12. Hideo Himeno
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  13. Takanori Ohkusa
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  14. Susumu Fujino
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  15. Makoto Shimizu
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  16. Tsutomu Endo
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  17. Shunichi Yoda
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  18. Takahiro Muroya
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  19. Toyoaki Murohara
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  20. Nobuyuki Ohte
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  21. Hiroshi Suzuki
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  22. Tohru Kohno
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  23. Kazuki Fukui
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  24. Takaaki Shiono
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  25. Hiroyuki Takase
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  26. Hiroyasu Uzui
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  27. Yoshiyuki Nagai
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  28. Yuji Hashimoto
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  29. Shuntaro Ikeda
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  30. Sumio Mizuno
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  31. Koichi Tamita
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  32. Masashi Fujita
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  33. Kazuo Satake
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  34. Yoshihiko Kinoshita
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  35. Tatsuya Nunohiro
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  36. Satoru Sakagami
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  37. Jitsuo Higaki
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  38. Isao Morii
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  39. Reimin Sawada
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  40. Yoshikazu Hiasa
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  41. Tomohiko Shigemasa
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  42. Makoto Nakahama
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  43. Masataka Sata
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  44. Osamu Doi
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  45. Tetsuro Ueda
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  46. Takahisa Yamada
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  47. Takayoshi Yamanouchi
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  48. Hajime Yamaguchi
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  49. Yukiko Morita
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  50. Hideki Hayashi
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  51. Masafumi Kitakaze
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Consortia

ABC investigators

Corresponding author

Correspondence to Masafumi Kitakaze.

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Sources of Funding

This study was supported by Grants on Comprehensive Research on Aging and Health in Health and Labor Sciences Research from the Ministry of Health, Labor and Welfare, Japan.

Conflict of Interest

Dr. Asakura reports grants and personal fees from Pfizer, grants from Takeda Pharmaceutical, personal fees from Mitsubishi Tanabe Pharma, and personal fees from Nippon Boehringer Ingelheim, personal fees from Kowa Pharmaceutical.

Dr. Asanuma reports personal fees from Kowa Pharmaceutical and personal fees from Otsuka Pharmaceutical.

Dr. Hamasaki reports personal fees from Mitsubishi Tanabe Pharma and personal fees from Parexel International.

Dr. Tsukahara reports grants from Japan Heart Foundation, during the conduct of the study; grants and personal fees from Daiichi-Sankyo; grants from Astra Zeneca; personal fees from Takeda Pharmaceutical; personal fees from Sanofi; personal fees from Astra Zeneka; personal fees from Bayer Yakuhin; and personal fees from Nippon Boehringer Ingelheim.

Dr. Ishikawa reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Nakama reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Koba reports grants from Japan Heart Foundation, during the conduct of the study; grants from MSD; grants from Mochida; personal fees from Astra Zeneca; personal fees from Takeda Pharmaceutical; personal fees from Novartis Phama; personal fees from Shionogi Pharm; personal fees from Daiichi-Sankyo; personal fees from Mitsubishi Tanabe Pharma; and personal fees from Pfizer.

Dr. Tsujimoto reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Astellas Pharma; personal fees from Otsuka Pharmaceutical; personal fees from Kyowa Hakko Kirin; personal fees from Kowa Pharmaceutical; personal fees from Sanofi; personal fees from Shionogi Pharm; personal fees from Daiichi-Sankyo; personal fees from Taisho Pharmaceutical; personal fees from Takeda Pharmaceutical; personal fees from Mitsubishi Tanabe Pharma; personal fees from Toa Eiyo; personal fees from Nippon Boehringer Ingelheim; personal fees from Bayer Yakuhin; personal fees from Pfizer; personal fees from Bristol-Myers; personal fees from Mochida Pharmaceutical; personal fees from Abbott Vascular; personal fees from Shimadzu; personal fees from Terumo; personal fees from Biosensors; personal fees from Medtronic; personal fees from Biotronik; personal fees from Fukuda Denshi; and personal fees from Boston Scientific.

Dr. Ohkusa reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Fujino reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Shimizu reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Yokohama City Fire Bureau; personal fees from The Japanese Society of Internal Medicine; personal fees from Yokohama izumi-ku Medical Association; personal fees from Yokohama City University; personal fees from St. Marianna University School of Medicine; personal fees from Kowa Pharmaceutical; personal fees from Nippon Boehringer Ingelheim; personal fees from Astelles Pharma; and personal fees from Otsuka Pharmaceutical, outside the submitted work.

Dr. Endo reports grants from Japan Heart Foundation, during the conduct of the study; grants and personal fees from Novartis; personal fees from Daiichi-sankyo; personal fees from Takeda; personal fees from Kyowa Hakko Kirin; personal fees from Eaisai; and grants from Public Health Research Foundation.

Dr. Yoda reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Muroya reports grants from Japan Heart Foundation, during the conduct of the study; grants from Public Health Research Foundation; personal fees from Boehringer Ingelheim; personal fees from Terumo; personal fees from Kowa Pharmaceutical; personal fees from Abbott Vascular; and personal fees from Daiichi-Sankyo.

Dr. Murohara reports grants from Japan Heart Foundation; grants and personal fees from Takeda Pharmaceutical, during the conduct of the study; grants from Teijin Pharma; grants from Astellas Phama; grants and personal fees from Nippon Boehringer Ingelheim; grants and personal fees from MSD; grants from Bristol-Myers; grants and personal fees from Takeda Pharmaceutical; grants from Daiichi-Sankyo; grants from Eisai; grants from Otsuka Pharmaceutical; grants and personal fees from Mitsubishi Tanabe Pharma; grants from Sumitomo Dainippon Pharma; and personal fees from Bayer Yakuhin.

Dr. Ohte reports grants from Japan Heart Foundation, during the conduct of the study; grants and personal fees from Takeda Pharmaceutical; grants and personal fees from Daiichi-Sankyo; grants and personal fees from MSD; grants and personal fees from Othuka Pharmaceutical; grants and personal fees from Kowa Pharmaceutical; grants and personal fees from Sumitomo Dainippon Pharma; grants and personal fees from Nippon Boehringer Ingelheim; grants and personal fees from Bayer Yakuhin; grants and personal fees from Astellas Pharma; grants and personal fees from Mitsubishi Tanabe Pharma; grants and personal fees from Actelion Pharmaceuticals; personal fees from Sanwa kagaku kenkyusho; personal fees from Astra Zeneca; personal fees from General Electric; personal fees from Siemens; personal fees from Toshiba; and personal fees from Toa Eiyo.

Dr. Suzuki reports grants from Japan Heart Foundation, during the conduct of the study; grants from Foundation for Biomedical Research and Innovation; grants from Japan Heart Foundation; grants from Astellas Phama; grants from Abbott Vascular; grants and personal fees from MSD; grants and personal fees from Otsuka Pharmaceutical; grants from Ono Pharmaceutical; grants from Kyowa Hakko Kirin; grants from Kowa Pharmaceutical; grants from Sanofi; grants and personal fees from Shionogi Pharm; grants and personal fees from Daiichi-Sankyo; grants and personal fees from Takeda Pharmaceutical; grants from Mitsubishi Tanabe Pharma; grants from Chugai Pharma; grants from Novartis Phama; grants from Nihon Medi-Physics; grants from Bayer Yakuhin; grants and personal fees from Pfizer; grants from Nippon Boehringer Ingelheim; grants from JCT; grants from Terumo; and personal fees from Astra Zeneca.

Dr. Kohno reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Fukui reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Takeda; personal fees from Eisai; personal fees from Bayer Yakuhin; personal fees from Mochida; personal fees from Bristol-Myers; personal fees from Kowa Pharmaceutical; personal fees from Astellas Pharma; personal fees from Otsuka Pharmaceutical; personal fees from AstraZeneca; personal fees from Nihon Medi-Physics; personal fees from Daiichi-Sankyo; and personal fees from Nippon Boehringer Ingelheim, outside the submitted work.

Dr. Shiono reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Takeda Pharmaceutical; personal fees from Daiichi-Sankyo; personal fees from Nippon Boehringer Ingelheim; personal fees from Bayer Yakuhin; personal fees from Mochida Pharmaceutical; personal fees from Kyowa Hakko Kirin; personal fees from Pfizer; personal fees from MSD; and personal fees from Otsuka Pharmaceutical.

Dr. Takase reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from MSD; personal fees from Astellas Pharma; personal fees from AstraZeneca; personal fees from Ono Pharmaceutical; personal fees from Sanwa kakagu kenkyusho; personal fees from Medical View; personal fees from Medical Tribune; personal fees from Kowa Pharmaceutical; personal fees from Sanofi; personal fees from Shionogi; personal fees from Daiichi-Sankyo; personal fees from Sumitomo Dainippon; personal fees from Takeda Pharmaceutical; personal fees from Toa Eiyo; personal fees from Nippon Boehringer Ingelheim; personal fees from Novartis Pharma; personal fees from Bayer Yakuhin; personal fees from Pfizer; personal fees from Fujifilm Ri Pharma; personal fees from Bristol-Myers; and personal fees from Mochida.

Dr. Uzui reports grants from Japan Heart Foundation, during the conduct of the study; grants from Fukui Medical Instruments; grants from Mochida Pharmaceutical; and grants from Bolnono.

Dr. Nagai reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Kyowa Hakko Kirin; personal fees from Bayer Yakuhin; personal fees from Mochida; personal fees from Daiichi-Sankyo; personal fees from Kowa Pharmaceutical; personal fees from Novartis Phama; personal fees from Takeda Pharmaceutical; personal fees from MSD; personal fees from Astellas Pharma; personal fees from Nippon Shinyaku; personal fees from Nippon Boehringer Ingelheim; personal fees from Eli Lilly Japan; personal fees from Sanofi; personal fees from Mitsubishi Tanabe Pharma; personal fees from Eisai; personal fees from Toa Pharmaceutical; and personal fees from Bristol-Myers.

Dr. Hashimoto reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Mizuno reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Tamita reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Medtronic; personal fees from Otsuka Pharmaceutical; personal fees from Abbtt Vascular; personal fees from Nipro; personal fees from St. Jude Medical; personal fees from Nippon Boehringer Ingelheim; personal fees from Bristol-Myers; and personal fees from Ono Pharmaceutical.

Dr. Fujita reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Satake reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Kinoshita reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Nunohiro reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Otsuka Pharmaceutical; personal fees from Bayer Yakuhin; personal fees from Sumitomo Dainippon Pharma; personal fees from Takeda Pharmaceutical; and personal fees from Kowa Pharmaceutical.

Dr. Sakagami reports grants from Japan Heart Foundation, during the conduct of the study; grants from Bayer Yakuhin; grants from Takeda Pharmaceutical; grants from Otsuka Pharmaceutical; grants and personal fees from Daiichi-Sankyo; grants from Astra Zeneca; grants from Pfizer; grants from Novartis Pharma; grants from Amgen; grants and personal fees from Nippon Boehringer Ingelheim; personal fees from Bayer Yakuhin; personal fees from Otsuka Pharmaceutical; personal fees from Johnson&Johnson; personal fees from St. Jude Medical; personal fees from Medtronic Japan; and personal fees from Bristol-Myers.

Dr. Higaki reports grants from Japan Heart Foundation, during the conduct of the study; grants and personal fees from Asteras Pharm; grants and personal fees from Nippon Boehringer-Ingelheim; grants and personal fees from Takeda Industrial; grants and personal fees from Mochida; grants and personal fees from MSD; grants and personal fees from Diichi-Sankyo; grants and personal fees from Phaisar; grants and personal fees from Novartis; grants and personal fees from Shionogi Pharm; grants and personal fees from Kowa Pharm; grants from Dainihon-Sumitomo; and personal fees from Actelion Pharm.

Dr. Morii reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Sawada reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Pfizer; personal fees from Takeda Pharmaceutical; and personal fees from Bayer Yakuhin.

Dr. Shigemasa reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Eisai; personal fees from Astellas Pharma; and personal fees from Novartis Pharma.

Dr. Nakahama reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Sata reports grants from Japan Heart Foundation, during the conduct of the study; grants and personal fees from Bayer Yakuhin; grants from Ono Pharmaceutical; grants and personal fees from Daiichi-Sankyo; grants and personal fees from Nippon Boehringer Ingelheim; grants and personal fees from Novartis Phama; grants and personal fees from Takeda Pharmaceutical; grants and personal fees from Mitsubishi Tanabe; grants and personal fees from Astellas Phama; grants and personal fees from MSD; personal fees from Mochida Pharmaceutical; personal fees from Shionogi Pharm; and personal fees from Astra Zeneca.

Dr. Doi reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Ueda reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Sumitomo Dainippon Pharma; and personal fees from Nippon Boehringer Ingelheim.

Dr. Yamanouchi reports grants from Japan Heart Foundation, during the conduct of the study; personal fees from Daiichi-Sankyo; personal fees from Nippon Boehringer Ingelheim; personal fees from Bayer Yakuhin; personal fees from Takeda Pharmaceutical; and personal fees from Mochida Pharmaceutical.

Dr. Yamaguchi reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Morita reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Hayashi reports grants from Japan Heart Foundation, during the conduct of the study.

Dr. Kitakaze reports grants and personal fees from Takeda, during the conduct of the study; grants from Japanese government; grants from Japan Heart Foundation; grants from Japan Cardiovascular Research Foundation; grants and personal fees from Asteras; grants and personal fees from Sanofi; personal fees from Daiichi-sankyo; grants and personal fees from Pfizer; grants and personal fees from Ono; personal fees from Bayer; grants and personal fees from Novartis; personal fees from Bheringer; grants and personal fees from Tanabe-mitubishi; personal fees from Kowa; grants and personal fees from Kyowa Hakko Kirin; personal fees from Dainihon-sumitomo; personal fees from Sawai; personal fees from MSD; grants and personal fees from Abott; grants and personal fees from Otsuka; grants from Calpis; grants from Nihon Kohden; personal fees from Shionogi; personal fees from Astrazeneca; personal fees from Asahikasei Med.; personal fees from Novo Nordisk; personal fees from Fujifilm RI; and personal fees from Japan Medical Data.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Electronic Supplementary Material

ESM 1

Supplementary Fig. 1: 95% Predicted interval plot for hazards ratio at the time of interim analysis. The DSMB used the unfixed data for this analysis. (PPTX 58 kb).

ESM 2

(DOCX 31 kb).

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Asakura, M., Kim, J., Asanuma, H. et al. Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?. Cardiovasc Drugs Ther 31, 401–411 (2017). https://doi.org/10.1007/s10557-017-6740-3

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