VADT: Legacy effect fizzles out over time
medwireNews: The 15-year results of the VADT reveal that the legacy cardioprotective effect of intensive glycemic control seen at the 10-year follow-up has now disappeared.
The investigators presented their results in a dedicated session at the ADA’s 78th Scientific Sessions in Orlando, Florida, USA, during which the independent commentator Hertzel Gerstein (McMaster University, Hamilton, Ontario, Canada) noted: “A legacy may not last forever. People squander their inheritance and the legacy is gone.”
The 15-year follow-up involved 1655 patients, including 1391 (78%) who had agreed to participate in an annual survey that covered items including their quality of life, major outcome events, and their vision.
Outlining these aspects of the trial, Wyndy Wiitala (VA Centre for Clinical Management Research, Ann Arbor, Michigan, USA) reminded conference attendees that the VADT participants had a starting glycated hemoglobin (HbA1c) of 9.4%, and randomization to intensive or standard glycemic control resulted in an average difference of 1.5%, over a median treatment period of 5.6 years.
This active treatment phase produced a nonsignificant 12% reduction in the primary composite macrovascular outcome of myocardial infarction, stroke, cardiovascular death, new or worsening heart failure, amputation for ischemic gangrene, vascular surgery, or inoperable heart disease. By the end of this phase, it appeared that the two groups were starting to separate in terms of macrovascular events, and this was confirmed in the 10-year analysis, which found a significant 17% reduction in patients who had been in the intensive treatment group.
This was despite the fact that HbA1c levels in the two groups had converged soon after the end of active treatment. Peter Reaven (Phoenix VA Healthcare System, Arizona, USA), who presented the macrovascular outcomes, noted that levels converged at an average of 8.4%, having been well controlled during intensive treatment, “illustrating the difficulty in controlling hemoglobin A1c values to this level in this advanced diabetes population.”
By the 15-year follow-up, not only had HbA1c levels converged but also the cardioprotective effect of having been in the intensive treatment group had disappeared, leaving a nonsignificant 9% risk difference in favor of intensive treatment.
During years 0 to 10 of the trial, when there was separation of HbA1c values between the groups, there was a significant 17% reduction in macrovascular event risk with intensive treatment, whereas during years 11 to 15 there was a nonsignificant 26% increased risk.
This means that “substantial and continuous glucose separation may be required to maintain” cardioprotective effects, Reaven concluded. He also noted that patients in the intensive group gained more weight than those in the standard treatment group, and this persisted over the whole follow-up.
Nicholas Emanuele (Hines VA Hospital, Loyola University of Chicago, Illinois, USA) reported a similar story for kidney outcomes, with the apparent legacy effect at the 10-year follow-up disappearing by year 15. By contrast, the combined retinal outcome, which had not been influenced by previous intensive treatment at the 10-year follow-up, was borderline significant in this latest analysis. Patients’ self-assessment of their visual acuity was unaffected, as was their risk for cataracts.
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