Long-Term Follow-Up of VADT Study Suggests Cardiovascular Benefits of Tight-Glucose Control in Diabetes
BACKGROUND:
Patients with type 2 diabetes have a greatly increased risk of cardiovascular events; therefore, learning whether improved glucose control reduces cardiovascular events is critically important. The Veterans Affairs Diabetes Trial (VADT) previously reported that intensive glucose lowering, compared to standard therapy, did not significantly reduce major cardiovascular events in 1,791 Veterans. VADT participants were randomly assigned to receive either intensive or standard glucose control. The study ended on May 29, 2008, with a median follow-up, 5.6 years. This study analyzed an additional five years of observational follow-up data on VADT participants (through December 2013), thus achieving a total follow-up of 11.8 years for most study measures. VA, Medicare, and U.S. National Death Index data were used to identify procedures, hospitalizations, and death (cohort, 92% follow-up). Moreover, most study participants agreed to additional data collection through annual surveys and periodic chart reviews (cohort, 78% follow-up). The primary outcome was a composite of major cardiovascular events that included: heart attack, stroke, new congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death. Secondary outcomes included cardiovascular and all-cause mortality.
FINDINGS:
- The separation of hemoglobin A1C between the intensive and standard glucose control arms averaged 1.5% during the trial itself (median, 6.9% vs. 8.4%, respectively), and declined to 0.2-0.3% by three years after the trial ended.
- Veterans with type 2 diabetes randomized to intensive glucose control for a median of 5.6 years had a significant 17% relative reduction in major cardiovascular events after almost 10 years of total follow-up (8.6 events prevented per 1,000 person-years) compared to Veterans who received standard glucose therapy. However, intensive glucose control was not associated with a significant decrease in all-cause mortality after almost 12 years of follow-up.
IMPLICATIONS:
- Results provide further evidence that improved glycemic control can reduce major cardiovascular events. This potential benefit may be considered in conversations with patients, but balanced with the burdens and safety data for the specific glucose-lowering treatment being considered.
LIMITATIONS:
- This was an observational follow-up of an unblinded, randomized controlled trial. Differences other than glucose separation cannot be completely excluded, either during or after the trial.
- The survey cohort is a subset of the full-study population, and may not fully represent findings for the whole cohort.
AUTHOR/FUNDING INFORMATION:
This study was funded by VA's Cooperative Studies Program (CSP). Drs. Hayward and Wiitala are part of HSR&D's Center for Clinical Management Research located in Ann Arbor, MI. Drs. Bahn, Reda, Ge, and Emanuele are part of VA's CSP at the Hines VA Hospital in Hines, IL.
Hayward R, Reaven P, Wiitala W, Bahn G, Reda D, Ge L, McCarren M, Duckworth W, and Emanuele N. Follow-up of Glycemic Control and Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of Medicine. June 4, 2015;372(23):2197-2206.
