Intensified insulin-based glycaemic control after myocardial infarction: mortality during 20 year follow-up of the randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial

Ritsinger V, Malmberg K, Mårtensson A
Lancet Diabetes Endocrinol. 2014 May 12

Background

Control of glucose levels is very important in the prevention of complications of the microvasculature in patients with diabetes. It is, however, unclear whether strict glucose control has beneficial effects on the prevention of macrovascular complications and better survival, specifically in patients with existing cardiovascular (CV) disease.
Too strict glycaemic control might even increase CV mortality [1-3]. Glycaemic control which is achieved in patients who have just received the diagnosis type 2 diabetes could, however, prevent CV complications in the following ten years [4].
In the first Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial, intensive insulin-based glycaemic control resulted in 11% reduction of mortality at year 3-4, as compared with standard care at the time [5,6]. This study investigated mortality in patients from DIGAMI 1 on the long term, i.e. until 20 years after randomization. 620 patients with or without diabetes diagnosis, who enrolled with suspicion of acute myocardial infarction (MI) in the preceding 24 hours, participated and were randomised to insulin-based glycaemic control for at least 3 months, or to a control group that was treated with conventional glucose-lowering drugs. If deemed necessary by the treating physician, insulin treatment was also given to patients in the control group.

Main results

• At hospital discharge, 266 (87%) patients in the intensive treatment group received insulin, as compared with 133 (43%) of the control group. After 3 months there were 245 (80%) vs. 141 (45%) patients respectively, and after 1 year this was 220 (72%) vs. 141 (49%).
• After a year the mean decrease of HbA1c was greater in patients in the intensive treatment group (-0.9%, SD: 1.9) than in the control group (-0.4%, SD: 1.8, P=0.0063).
• Mean follow-up was 7.3 years (range: 0.0-21.8 years). At the end of the follow-up 556 (90%) patients had died: 271 (89%) in the intensive treatment group and 285 (91%) in the control group. There were no significant differences in causes of mortality between groups.
• The median survival time was significantly larger for patients in the intensive treatment group (7.0 years, IQR: 1.8-12.4) than in the control group (4.7 years, IQR: 1.0-11.4)(HR: 0.83, 95%CI: 0.70-0.98, P=0.027).
• Patients with a low risk and who did not previously receive insulin, had a significant survival benefit (HR: 0.77, 5%CI: 0.60-1.00, P=0.048), with an average survival time of 9.4 years (95%CI: 8.3-11.1) in the intensively treated group, as compared with the control group (6.9 years, 95%CI: 4.8-8.2). Risks did not significantly differ in the other strata based on high vs. low risk and yes/no previous insulin treatment.

Conclusion

These findings show that survival was improved in patients with type 2 diabetes after an acute MI, when they receive intensive insulin-based glycaemic control. This benefit lasted for at least 8 years. Patients with a high risk who had not beet treated with insulin previously, did not benefit from intensive insulin treatment, which confirms findings from the ACCORD and ADVANCE studies, that strict glycaemic control did not seem to improve survival of patients with longstanding diabetes and CV disease.
Based on these study results the concept of glycaemic control for the prevention of microvascular complications can be extended to the prevention of CV and overall mortality in patients with type 2 diabetes and apparently deranged glucose control.

Editorial comment [7]

Differences exist between various studies who test the long term effects of intensive glucose control and the DIGAMI 1 study, as a consequence of the available treatments, treatment goals and baseline HbA1c-levels. The 20 year follow-up results of the DIGAMI 1 trial will not change the treatment of a patient: in the meantime other glucose-lowering therapies have become available and physicians treat their patients already in such a way that they will reach glucose targets from DIGAMI 1.
The value of DIGAMI 1 is in its history: it points toward the need of good glucose control, even if other risk factors like lipids or blood pressure cannot be or have not been modified. Moreover, the study emphasizes how fast medicine is moving forward; in 20 years the treatment options have been largely expanded.

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References

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