EClinicalMedicine (Oct 2018)
Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment With Pioglitazone
- Masanori Asakura,
- Jiyoong Kim,
- Hiroshi Asanuma,
- Yasuharu Nakama,
- Kengo Tsukahara,
- Yorihiko Higashino,
- Tetsuya Ishikawa,
- Shinji Koba,
- Mitsuru Tsujimoto,
- Hideo Himeno,
- Yasuyuki Maruyama,
- Takanori Ookusa,
- Shunichi Yoda,
- Hiroshi Suzuki,
- Shinji Okubo,
- Makoto Shimizu,
- Yuji Hashimoto,
- Kazuo Satake,
- Susumu Fujino,
- Hiroyasu Uzui,
- Yoshiyuki Nagai,
- Tohru Kohno,
- Sumio Mizuno,
- Makoto Nakahama,
- Hounin Kanaya,
- Toyoaki Murohara,
- Kazuki Fukui,
- Hiroyuki Takase,
- Nobuyuki Ohte,
- Takaaki Shiono,
- Masatake Fukunami,
- Tsutomu Endo,
- Reimin Sawada,
- Kenshi Fujii,
- Motoshi Takeuchi,
- Shuntaro Ikeda,
- Koichi Mizuno,
- Masaaki Uematsu,
- Taku Matsubara,
- Shoji Yano,
- Jun Takahashi,
- Kousei Ueda,
- Yoshihiko Kinoshita,
- Koichi Tamita,
- Hideki Hayashi,
- Toshimitsu Hamasaki,
- Masafumi Kitakaze
Affiliations
- Masanori Asakura
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Division, Hyogo College of Medicine, Hyogo, Japan
- Jiyoong Kim
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan; Kim Cardiovascular Clinic, Osaka, Japan
- Hiroshi Asanuma
- Department of Internal Medicine, Meiji University of Integrative Medicine, Kyoto, Japan
- Yasuharu Nakama
- Department of Cardiology, Hiroshima City Hospital, Hiroshima, Japan
- Kengo Tsukahara
- Division of Cardiology, Yokohama City University Medical Center, Kanagawa, Japan
- Yorihiko Higashino
- Department of Cardiology, Higashi Takarazuka Satoh Hospital, Hyogo, Japan
- Tetsuya Ishikawa
- Department of Cardiology, Saitama Prefecture Cardiovascular and Respiratory Center, Saitama, Japan
- Shinji Koba
- Division of Cardiology, Department of Medicine, Showa University Hospital, Tokyo, Japan
- Mitsuru Tsujimoto
- Department of Cardiology, Cardiovascular Center, Veritas Hospital, Hyogo, Japan
- Hideo Himeno
- Division of Cardiology, Fujisawa City Hospital, Kanagawa, Japan
- Yasuyuki Maruyama
- Department of Cardiology, Iwatsuki-Minami Hospital, Saitama, Japan
- Takanori Ookusa
- Department of Cardiology, Hokko Memorial Hospital, Hokkaido, Japan
- Shunichi Yoda
- Division of Cardiology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan
- Hiroshi Suzuki
- Division of Cardiology, Showa University Fujigaoka Hospital, Kanagawa, Japan
- Shinji Okubo
- Department of Cardiovascular Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
- Makoto Shimizu
- Department of Cardiology, International Goodwill Hospital, Kanagawa, Japan
- Yuji Hashimoto
- Department of Cardiology, Kameda Medical Center, Chiba, Japan
- Kazuo Satake
- Department of Cardiology, Fukui General Clinic, Fukui, Japan
- Susumu Fujino
- Department of Cardiology, Fukui Prefectural Hospital, Fukui, Japan
- Hiroyasu Uzui
- Department of Cardiology, University of Fukui Hospital, Fukui, Japan
- Yoshiyuki Nagai
- Department of Cardiology, Rinku General Medical Center, Osaka, Japan
- Tohru Kohno
- Department of Cardiology, Tokyo Rinkai Hospital, Tokyo, Japan
- Sumio Mizuno
- Department of Internal Medicine, Fukui Cardiovascular Center, Fukui, Japan
- Makoto Nakahama
- Department of Cardiology, Fukuyama City Hospital, Hiroshima, Japan
- Hounin Kanaya
- Division of Cardiology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
- Toyoaki Murohara
- Department of Cardiology, Nagoya University, Aichi, Japan
- Kazuki Fukui
- Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan
- Hiroyuki Takase
- Department of Internal Medicine, Enshu Hospital, Shizuoka, Japan
- Nobuyuki Ohte
- Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
- Takaaki Shiono
- Department of Cardiology, Kitasato University Medical Center, Saitama, Japan
- Masatake Fukunami
- Division of Cardiology, Osaka General Medical Center, Osaka, Japan
- Tsutomu Endo
- Department of Cardiology, Saiseikai Yokohama City Southern Hospital, Kanagawa, Japan
- Reimin Sawada
- Department of Cardiology, Hadano Red Cross Hospital, Kanagawa, Japan
- Kenshi Fujii
- Department of Cardiology, Fukui Prefectural Hospital, Fukui, Japan
- Motoshi Takeuchi
- Department of Internal Medicine, Takeuchi Clinic, Hyogo, Japan
- Shuntaro Ikeda
- Division of Cardiology, Uwajima City Hospital, Ehime, Japan
- Koichi Mizuno
- Department of Cardiology, Kawasaki Municipal Tama Hospital, Kanagawa, Japan
- Masaaki Uematsu
- Cardiovascular Center, Kansai Rosai Hospital, Hyogo, Japan
- Taku Matsubara
- Department of Cardiovascular Medicine, Shinrakuen Hospital, Niigata, Japan
- Shoji Yano
- Department of Cardiovascular Medicine, Almeida Memorial Hospital, Oita, Japan
- Jun Takahashi
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan
- Kousei Ueda
- Division of Cardiology, Komatsu Municipal Hospital, Ishikawa, Japan
- Yoshihiko Kinoshita
- Department of Cardiology, Kinoshita Clinic, Hiroshima, Japan
- Koichi Tamita
- Department of Cardiology, Nishinomiya Watanabe Cardiovascular Center, Hyogo, Japan
- Hideki Hayashi
- Department of Internal Medicine, Hoetsu Hospital, Tokushima, Japan
- Toshimitsu Hamasaki
- Department of Data Science, National Cerebral and Cardiovascular Center, Osaka, Japan
- Masafumi Kitakaze
- Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Osaka, Japan; Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; Corresponding author at: Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center, Suita 565-8565, Japan.
- Journal volume & issue
-
Vol. 4
pp. 10 – 24
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. Keywords: Myocardial infarction, Diabetes mellitus, Pioglitazone, Blood glucose-lowering, Cardiovascular events, PROBE study
