Masanori Asakura1,2,3, Jiyoong Kim1,4, Hiroshi Asanuma5, Yasuharu Nakama6, Kengo Tsukahara7, Yorihiko Higashino8, Tetsuya Ishikawa9, Shinji Koba10, Mitsuru Tsujimoto11, Hideo Himeno12, Yasuyuki Maruyama13, Takanori Ookusa14, Shunichi Yoda15, Hiroshi Suzuki16, Shinji Okubo17, Makoto Shimizu18, Yuji Hashimoto19, Kazuo Satake20, Susumu Fujino21, Hiroyasu Uzui22, Yoshiyuki Nagai23, Tohru Kohno24, Sumio Mizuno25, Makoto Nakahama26, Hounin Kanaya27, Toyoaki Murohara28, Kazuki Fukui29, Hiroyuki Takase30, Nobuyuki Ohte31, Takaaki Shiono32, Masatake Fukunami33, Tsutomu Endo34, Reimin Sawada35, Kenshi Fujii21, Motoshi Takeuchi36, Shuntaro Ikeda37, Koichi Mizuno38, Masaaki Uematsu39, Taku Matsubara40, Shoji Yano41, Jun Takahashi42, Kousei Ueda43, Yoshihiko Kinoshita44, Koichi Tamita45, Hideki Hayashi46, Toshimitsu Hamasaki47, Masafumi Kitakaze1,2. 1. Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan. 2. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan. 3. Department of Cardiovascular Division, Hyogo College of Medicine, Hyogo, Japan. 4. Kim Cardiovascular Clinic, Osaka, Japan. 5. Department of Internal Medicine, Meiji University of Integrative Medicine, Kyoto, Japan. 6. Department of Cardiology, Hiroshima City Hospital, Hiroshima, 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. Division of Cardiology, Department of Medicine, Showa University Hospital, Tokyo, Japan. 11. Department of Cardiology, Cardiovascular Center, Veritas Hospital, Hyogo, Japan. 12. Division of Cardiology, Fujisawa City Hospital, Kanagawa, Japan. 13. Department of Cardiology, Iwatsuki-Minami Hospital, Saitama, Japan. 14. Department of Cardiology, Hokko Memorial Hospital, Hokkaido, Japan. 15. Division of Cardiology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. 16. Division of Cardiology, Showa University Fujigaoka Hospital, Kanagawa, Japan. 17. Department of Cardiovascular Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan. 18. Department of Cardiology, International Goodwill Hospital, Kanagawa, Japan. 19. Department of Cardiology, Kameda Medical Center, Chiba, Japan. 20. Department of Cardiology, Fukui General Clinic, Fukui, Japan. 21. Department of Cardiology, Fukui Prefectural Hospital, Fukui, Japan. 22. Department of Cardiology, University of Fukui Hospital, Fukui, Japan. 23. Department of Cardiology, Rinku General Medical Center, Osaka, Japan. 24. Department of Cardiology, Tokyo Rinkai Hospital, Tokyo, Japan. 25. Department of Internal Medicine, Fukui Cardiovascular Center, Fukui, Japan. 26. Department of Cardiology, Fukuyama City Hospital, Hiroshima, Japan. 27. Division of Cardiology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan. 28. Department of Cardiology, Nagoya University, Aichi, Japan. 29. Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan. 30. Department of Internal Medicine, Enshu Hospital, Shizuoka, Japan. 31. Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. 32. Department of Cardiology, Kitasato University Medical Center, Saitama, Japan. 33. Division of Cardiology, Osaka General Medical Center, Osaka, Japan. 34. Department of Cardiology, Saiseikai Yokohama City Southern Hospital, Kanagawa, Japan. 35. Department of Cardiology, Hadano Red Cross Hospital, Kanagawa, Japan. 36. Department of Internal Medicine, Takeuchi Clinic, Hyogo, Japan. 37. Division of Cardiology, Uwajima City Hospital, Ehime, Japan. 38. Department of Cardiology, Kawasaki Municipal Tama Hospital, Kanagawa, Japan. 39. Cardiovascular Center, Kansai Rosai Hospital, Hyogo, Japan. 40. Department of Cardiovascular Medicine, Shinrakuen Hospital, Niigata, Japan. 41. Department of Cardiovascular Medicine, Almeida Memorial Hospital, Oita, Japan. 42. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan. 43. Division of Cardiology, Komatsu Municipal Hospital, Ishikawa, Japan. 44. Department of Cardiology, Kinoshita Clinic, Hiroshima, Japan. 45. Department of Cardiology, Nishinomiya Watanabe Cardiovascular Center, Hyogo, Japan. 46. Department of Internal Medicine, Hoetsu Hospital, Tokushima, Japan. 47. Department of Data Science, National Cerebral and Cardiovascular Center, Osaka, Japan.
Abstract
BACKGROUND: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. METHODS: In this multicentre, prospective, randomised, open, blinded-endpoint trial, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. FINDINGS: HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p < 0·01) at 2 years for the control and pioglitazone groups, respectively.The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years (95% confidential interval (CI):0.662-1·526, p = 0·98), respectively; the incidence of MI and cerebral infarction was 0·3% and 2·2% (95%CI: 0·786-32·415, p = 0·09) and 1·0% and 0·3% (95%CI: 0·051-3·662, p = 0·44), respectively. Post-hoc analyses of the 7-year observation period showed that these trends were comparable (21·9% and 19·2% in the control and pioglitazone groups, 95%CI: 0.618-1·237, p = 0·45). INTERPRETATION: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI.
BACKGROUND: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. METHODS: In this multicentre, prospective, randomised, open, blinded-endpoint trial, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. FINDINGS: HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p < 0·01) at 2 years for the control and pioglitazone groups, respectively.The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years (95% confidential interval (CI):0.662-1·526, p = 0·98), respectively; the incidence of MI and cerebral infarction was 0·3% and 2·2% (95%CI: 0·786-32·415, p = 0·09) and 1·0% and 0·3% (95%CI: 0·051-3·662, p = 0·44), respectively. Post-hoc analyses of the 7-year observation period showed that these trends were comparable (21·9% and 19·2% in the control and pioglitazone groups, 95%CI: 0.618-1·237, p = 0·45). INTERPRETATION: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI.
Authors: Daniel Levy; Satish Kenchaiah; Martin G Larson; Emelia J Benjamin; Michelle J Kupka; Kalon K L Ho; Joanne M Murabito; Ramachandran S Vasan Journal: N Engl J Med Date: 2002-10-31 Impact factor: 91.245