Outcomes out to 5 years in the ACCORD trial are consistent with those that brought the study to a halt after a mean of 3.7 years of intensive glucose-lowering therapy reduced the risk of nonfatal myocardial infarction in patients with advanced type 2 diabetes and a high risk of cardiovascular disease, but increased the risk of death.
Thus, a therapeutic approach that targets glycated hemoglobin levels below 6% cannot be recommend in this population, Dr. Hertzel C. Gerstein of McMaster University, Hamilton, Ont., and colleagues from the Action to Control Cardiovascular Risk in Diabetes Study Group reported.
ACCORD participants were 10,108 type 2 diabetes patients with cardiovascular disease who were randomly assigned to receive intensive glucose-lowering therapy to a target hemoglobin A1c below 6.0% or to standard therapy with a target HbA1c of 7.0%–7.9%. The intensive therapy was terminated after a mean of 3.5 years because of higher mortality in the intensive treatment group, and patients from that group began receiving standard therapy. The current findings reflect an additional 0.2 months of intensive therapy not previously reported, and up to 17 months of additional follow-up.
Prior to the transition, the incidence of the primary outcome (a composite of nonfatal MI, nonfatal stroke, or death from cardiovascular causes) was 2.0% per year in the intensive therapy group, and 2.2% per year in the standard therapy group (hazard ratio 0.90).
Although the intensive therapy did lower the rate of nonfatal MI (1.08% vs. 1.35%, HR 0.79), it was also associated with a nonsignificant increased rate of death from cardiovascular causes (0.71% vs. 0.55%, HR 1.27).
“These divergent effects were retained at the end of the study, with a rate of nonfatal MI in the intensive-therapy groups that was lower than in the standard-therapy group (1.18 vs. 1.42; hazard ratio 0.82) … and a rate of death from cardiovascular causes that was higher (0.74 vs. 0.57; hazard ratio 1.29),” they found (N. Engl. J. Med. 2011;364:818-28).
At the time of transition, the death rate from any cause was a significant 21% higher in the intensive therapy group (1.42 vs. 1.16), and it remained higher – by 19% – at the end of the study (1.53 vs. 1.27).
The findings indicate that 3.7 years of intensive therapy to target normal HbA1c in a high-risk population does not significantly lower the number of major cardiovascular events after 5 years, compared with therapy that targets “levels that are more typically achieved in person in the United States and Canada (i.e., 7–7.9%),” and indeed, the intensive approach was associated with more deaths, they said.
ACCORD was supported by the National Institutes of Health and the Centers for Disease Control and Prevention. Study medication, equipment, or supplies were provided by numerous pharmaceutical companies. Dr. Gerstein has received consulting fees, institutional grant support, and/or lecture fees from Sanofi-Aventis, GlaxoSmithKline, Novo Nordisk, and several other drug companies. Individual ACCORD Study Group members' disclosures are available with the full text of the article at www.nejm.com
HbA1c levels below 6% should be avoided, said Dr. Hertzel C. Gerstein.
Source Courtesy McMaster University