Masanori Asakura1,2, Jiyoong Kim1, Hiroshi Asanuma3,4, Toshimitsu Hamasaki5,6, Kengo Tsukahara7, Yorihiko Higashino8, Tetsuya Ishikawa9, Yasuharu Nakama10, Shinji Koba11, Yasuyuki Maruyama12, Mitsuru Tsujimoto13, Hideo Himeno14, Takanori Ohkusa15, Susumu Fujino16, Makoto Shimizu17, Tsutomu Endo18, Shunichi Yoda19, Takahiro Muroya20, Toyoaki Murohara21, Nobuyuki Ohte22, Hiroshi Suzuki23, Tohru Kohno24,25, Kazuki Fukui26, Takaaki Shiono27, Hiroyuki Takase28, Hiroyasu Uzui29, Yoshiyuki Nagai30, Yuji Hashimoto31, Shuntaro Ikeda32, Sumio Mizuno33, Koichi Tamita34, Masashi Fujita35, Kazuo Satake36, Yoshihiko Kinoshita37, Tatsuya Nunohiro38,39, Satoru Sakagami40, Jitsuo Higaki41, Isao Morii42, Reimin Sawada43, Yoshikazu Hiasa44, Tomohiko Shigemasa45, Makoto Nakahama46, Masataka Sata47, Osamu Doi48, Tetsuro Ueda49, Takahisa Yamada50, Takayoshi Yamanouchi51, Hajime Yamaguchi52, Yukiko Morita53, Hideki Hayashi54, Masafumi Kitakaze55,56. 1. Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center Suita, Osaka, 565-8565, Japan. 2. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan. 3. Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan. 4. Cardiovascular Science and Technology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 5. Department of Biomedical Statistics, Osaka University Graduate School of Medicine, Suita, Japan. 6. Department of Data Science, National Cerebral and Cardiovascular Center, Osaka, Japan. 7. Division of Cardiology, Yokohama City University Medical Center, Kanagawa, Japan. 8. Department of Cardiology, Higashi Takarazuka Satoh Hospital, Hyogo, Japan. 9. Department of Cardiology, Saitama Prefecture Cardiovascular and Respiratory Center, Saitama, Japan. 10. Department of Cardiology, Hiroshima City Hospital, Hiroshima, Japan. 11. Division of Cardiology, Department of Medicine, Showa University Hospital, Tokyo, Japan. 12. Department of Cardiology, Iwatsuki-minami Hospital, Saitama, Japan. 13. Department of Cardiology, Cardiovascular Center, Veritas Hospital, Hyogo, Japan. 14. Division of Cardiology, Fujisawa City Hospital, Kanagawa, Japan. 15. Department of Cardiology, Hokko Memorial Hospital, Hokkaido, Japan. 16. Department of Cardiology, Fukui Prefectural Hospital, Fukui, Japan. 17. Department of Cardiology, International Goodwill Hospital, Kanagawa, Japan. 18. Department of Cardiology, Saiseikai Yokohama City Southern Hospital, Kanagawa, Japan. 19. Division of Cardiology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. 20. Department of Cardiology, National Hospital Organization Ureshino Medical Center, Saga, Japan. 21. Department of Cardiology, Nagoya University Graduate School of Medicine, Aichi, Japan. 22. Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. 23. Division of Cardiology, Showa University Fujigaoka Hospital, Kanagawa, Japan. 24. Department of Cardiology, Tokyo Rinkai Hospital, Tokyo, Japan. 25. Department of Cardiology, Kasukabe Municipal Hospital, Saitama, Japan. 26. Division of Cardiology, Kanagawa Cardiovascular Respiratory Center, Kanagawa, Japan. 27. Department of Cardiology, Kitasato University Medical Center, Saitama, Japan. 28. Department of Internal Medicine, Enshu Hospital, Shizuoka, Japan. 29. Department of Cardiology, Fukui University Hospital, Fukui, Japan. 30. Department of Cardiology, Rinku General Medical Center, Osaka, Japan. 31. Department of Cardiology, Kameda Medical Center, Chiba, Japan. 32. Division of Cardiology, Uwajima City Hospital, Ehime, Japan. 33. Department of Cardiology, Fukui Cardiovascular Center, Fukui, Japan. 34. Department of Cardiology, Nishinomiya Watanabe Cardiovascular Center, Hyogo, Japan. 35. Department of Cardiovascular Division, Kansai Rosai Hospital, Hyogo, Japan. 36. Department of Cardiology, Fukui General Clinic, Fukui, Japan. 37. Kinoshita Clinic, Hiroshima, Japan. 38. Department of Cardiology, Nagasaki Municipal Hospital, Nagasaki, Japan. 39. Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan. 40. Department of Cardiology, National Hospital Organization Kanazawa Medical Center, Ishikawa, Japan. 41. Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Ehime, Japan. 42. Department of Cardiology, Hokusetsu General Hospital, Osaka, Japan. 43. Department of Cardiology, Hadano Red Cross Hospital, Kanagawa, Japan. 44. Department of Cardiology, Tokushima Red Cross Hospital, Tokushima, Japan. 45. Department of Cardiovascular Medicine, International University of Health and Welfare Atami Hospital, Shizuoka, Japan. 46. Department of Cardiology, Fukuyama City Hospital, Hiroshima, Japan. 47. Department of Cardiovascular Medicine, University of Tokushima, Tokushima, Japan. 48. Department of Cardiology, Shizuoka Prefectural General Hospital, Shizuoka, Japan. 49. Department of Cardiology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan. 50. Division of Cardiology, Osaka General Medical Center, Osaka, Japan. 51. Department of Cardiology, Department of Internal Medicine, Hitachi, Ltd. Hitachinaka General Hospital, Ibaraki, Japan. 52. Yamaguchi Clinic, Fukushima, Japan. 53. Department of Cardiology, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan. 54. Department of Internal Medicine, Hoetsu Hospital, Tokurshima, Japan. 55. Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center Suita, Osaka, 565-8565, Japan. kitakaze@hsp.ncvc.go.jp. 56. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan. kitakaze@hsp.ncvc.go.jp.
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.
RCT Entities:
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.
Authors: Ruth L Coleman; Charles A B Scott; Zhihui Lang; M Angelyn Bethel; Jaakko Tuomilehto; Rury R Holman Journal: Cardiovasc Diabetol Date: 2019-10-17 Impact factor: 9.951
Authors: Suzanne Vl Moelands; Peter Lbj Lucassen; Reinier P Akkermans; Wim Jc De Grauw; Floris A Van de Laar Journal: Cochrane Database Syst Rev Date: 2018-12-28