Less Is Not Too Much More: Extended Follow-Up of the Veterans Affairs Diabetes Trial | Journal Scan

Study Questions:

What are cardiovascular outcomes and overall survival rates during extended follow-up of patients participating in the VADT (Veterans Affairs Diabetes Trial) study, in which participants were randomized to intensive glucose-lowering or standard therapy?

Methods:

This was a prespecified analysis with observational follow-up of patients in the VADT study. The original trial included 1,791 patients with type 2 diabetes who were randomly assigned to receive either intensive or standard glucose control. The interventional component of the study ended on May 29, 2008, after a median follow-up of 5.6 years. At the conclusion of the trial, all participants returned to usual care with no further clinical intervention by the research team. The primary outcome was the time to the first major cardiovascular event (myocardial infarction, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Follow-up data were collected through national data registries (VA medical information files, the Centers for Medicare and Medicaid Services [CMS] Medicare claims files, the VA death files, and the National Death Index).

Results:

In the survey cohort, 77.7% of participants agreed to additional data collection (annual surveys, periodic chart reviews) after the original study had ended. Although the difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.3%), this declined to 0.2-0.3 percentage points by 3 years after the trial ended. At 9.8 years of follow-up, 288 major cardiovascular events had occurred in the standard-therapy group, as compared with 253 in the intensive-therapy group; the intensive-therapy group, accordingly, had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval, 0.70-0.99; p = 0.04). However, there were no significant between-group differences in either cardiovascular mortality or all-cause mortality.

Conclusions:

Extended follow-up of patients in the VADT demonstrates a significant reduction in time to first major cardiovascular event; however, there was no evidence of an improved rate of overall survival.

Perspective:

This is an important analysis, albeit with limitations, that demonstrates intensive glucose control was not associated with a significant decrease in all-cause mortality after almost 12 years of follow-up. That said, this prespecified analysis was of participants who returned to usual care with no further clinical intervention; and the difference in glycated hemoglobin between the intensive-therapy and the standard-therapy groups declined to 0.2-0.3 percentage points by 3 years after the trial ended. Perhaps overall survival may have been different if the difference in glycated hemoglobin had actually been sustained. Nonetheless, the authors draw caution to a strategy of intensive glucose control when such an approach does not alter overall survival and contributes only a small-to-moderate reduction in the rate of cardiovascular events. Certainly and as the authors opine, aggressive glycemic control is not without consequences (i.e., weight gain, hypoglycemia).

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Amputation, Blood Glucose, Diabetes Mellitus, Type 2, Follow-Up Studies, Gangrene, Glucose, Heart Failure, Hemoglobin A, Glycosylated, Hypoglycemia, Medicaid, Medicare, Metabolic Syndrome X, Mortality, Myocardial Infarction, Primary Prevention, Registries, Stroke, Veterans, Weight Gain


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