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  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 Findings HbA1C levels were 5·9 and 5·8% (p = 0·71) at baseline and 6·0 and 5·8% (p  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.