Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D Trial
Raz I, Wilson PW, Strojek K, et al
Diabetes Care. 2009;32:381-386
Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized controlled trial designed to compare the effects of prandial vs fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (MI). This multinational trial was conducted in 17 countries. Within 21 days after an MI, 557 patients were randomly assigned to the prandial strategy (3 premeal doses of insulin lispro targeting 2-hour postprandial blood glucose < 135 mg/dL), and 558 patients were assigned to the basal strategy (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose < 121 mg/dL). The primary outcome was time until the first combined adjudicated cardiovascular event, defined as cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for acute coronary syndrome.
The Data Monitoring Committee recommended stopping the trial because of futility after the fourth interim analysis. The prandial and basal groups were similar in age, sex, origin, country, body mass index (BMI), duration of diabetes, and other clinically relevant measures. The number of prandial patients experiencing a first cardiovascular event was similar to that in the basal group (31.2% vs 32.4%; hazard ratio 0.98 [95% CI 0.80-1.21]). Glycated hemoglobin (HbA1c) did not differ between groups during the study. Approximately 47% of patients in the prandial group achieved the blood glucose target of < 135 mg/dL for daily mean postprandial blood glucose, and 46% in the basal group achieved daily mean fasting/premeal blood glucose < 121 mg/dL.
Research has shown that postprandial hyperglycemia is the most important contributor to HbA1c, especially when it is less than 7.5%. Thus, targeting postprandial hyperglycemia may help patients achieve glycemic targets. However, whether postprandial hyperglycemia is an independent risk factor for cardiovascular disease in diabetes is unclear. Unfortunately, the current study was unable to settle the debate. The HEART2D study was underpowered, and did not come close to achieving the targeted difference in postprandial hyperglycemia; therefore, the results are not surprising. Consistent with the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, ADVANCE (Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation) trial, and VADT (Veterans Affairs Diabetes Trial) results, these findings suggest that to realize benefits of glycemic control, intensive efforts probably need to begin sooner rather than later. From a practical standpoint, the negative results have a positive message. Many clinicians are reluctant to start patients on insulin because of complexity and uncertainty surrounding choices of therapy. The current study suggests that the basal and prandial approaches may be more or less equivalent in their therapeutic benefit; there was no difference between the basal and prandial groups in the HbA1c achieved. If so, clinicians and patients are free to choose the insulin therapy with which they are most comfortable, can afford, and are most inclined to use as directed.
Medscape Diabetes © 2009 Medscape, LLC
Cite this: Gregory A. Nichols. Insulin Control and Cardiovascular Outcomes in Patients With Diabetes - Medscape - May 19, 2009.