Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment With Pioglitazone: Reports of a Randomised Trial From The Japan Working Group for the Assessment Whether Pioglitazone Protects DM Patients Against Re-Infarction (PPAR Study).

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.

• Authors: 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, PPAR investigators
• Journal: EClinicalMedicine (EClinicalMedicine) 2018 Oct-Nov Vol. 4-5 Pg. 10-24 ISSN: 2589-5370 [Electronic] England
• PMID: 31193597 (Publication Type: Journal Article)