How to interpret results of the HEART2D trial?

HEART2D was a multinational, randomized, controlled trial designed to compare the effects of prandial insulin versus basal insulin on risk for subsequent cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (MI). Trial design was based on the hypothesis that 2.5 mmol/L postprandial blood glucose (BG) difference between groups would result in risk reduction of 19 to 23% over the planned follow up period (18-36 mo) in the group with lower postprandial BG. One thousand one hundred and fifteen (1115) patients were randomized [prandial strategy (N = 557), basal strategy (N = 558)]. HEART2D was stopped after futility rule implementation at the fourth interim analysis. The risk of a first combined adjudicated CV events in the prandial group (N = 174, 31.2%) and basal (N = 181, 32.4%) groups was similar (HR = 0.98; 95% CI [0.8, 1.21]). The results of HEART2D left the question of the role of postprandial hyperglycemia in diabetic CV disease unanswered. Here, we discuss possible reasons for this outcome, including characteristics of daily BG profiles in the two treatment groups, event rate, risk factors other than standard CV risk factors and glycemic variables. The main reasons for this outcome of HEART2D study could be smaller than expected on-study differences between the study groups in postprandial hyperglycemia, and low event rate. Further trials with larger patient populations and improved designs, focusing also on diabetic patients with lower cardiovascular risk and lower baseline HbA(1c) levels are needed in order to shed more light on this important clinical problem.