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ACCORD: Intensive glucose control increased relative risk for mortality in high-risk patients
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Recent findings from the ACCORD trial demonstrated that intensive glucose control to target <6% increased the relative risk for death compared with standard glucose control.
Patients assigned to intensified glucose lowering (n=5,128) had a 22% higher relative risk for death compared with patients assigned to standard glucose control (HbA1c 7% to 7.9%; n=5,123) — an absolute mortality increase of about 1% during 3.5 years of treatment and follow-up.
“The major clinical implication is that there is some risk associated with this level of intensification of glycemic control in high-risk cardiovascular patients with type 2 diabetes,” said Robert Byington, PhD, head of the ACCORD coordinating center and professor of epidemiology and prevention, Wake Forest University School of Medicine, Winston Salem, NC.
ACCORD was conducted to determine whether intensive glucose control could reduce the risk for CVD in high-risk patients with type 2 diabetes (61% men; 74% non-Hispanic white; mean age, 62). However, the Data Safety Monitoring Board terminated it in February due to increased deaths in the intensive treatment arm (257 vs. 203; P=.04). At termination, mean HbA1c was 6.4% in the intensive group vs. 7.5% in the standard group.
“Despite the fact that we achieved a good 1.1% difference in HbA1c levels between the two treatment groups, the intensive group patients only had a nonsignificant 10% lower risk of our primary outcome measure, a composite of nonfatal myocardial infarction, stroke or cardiovascular death,” Byington said (352 vs. 371).
The secondary outcome — rate of cardiovascular death due to MI, heart failure and arrhythmia — was 35% higher in the intensive group.
Additionally, hypoglycemia and weight gain more than 10 kg were more common among intensive therapy patients (P<.001).
“We have been unable to identify single agent or combination that accounts for the imbalance in mortality,” said Michael E. Miller, PhD, Wake Forest University School of Medicine.
ACCORD researchers plan to follow patients for at least another 18 months until 2009, when the study was scheduled to end, they said. – by Katie Kalvaitis
For more information:
- Goff DC, Ismail-Beigi F, Gerstein H, et al. ACCORD Trial — Study results. Presented at: ADA 68th Scientific Sessions; June 6-10, 2008; San Francisco
- Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2549.
The ACCORD glucose results will change opinion and some guidelines more than practice. Glycemic control in this country has clearly improved over the past decade but very few people are achieving goals recommended by the American Association of Clinical Endocrinologists and other international guidelines. Thus, relatively few people would be affected. Conversely, I do not think this will change ADA guideline recommendations of HbA1c <7% since the group between 6.5% and 7% did not have an increased risk of cardiovascular events. Based on the timing of data collection I do not think we will ever know why the cardiovascular event rate increased in the lower glucose control group; however, one cannot eliminate the possibility of early morning hypoglycemia and increased sympathetic tone as a contributing factor. In short, like hypertension control, it appears that glucose control has a U-shaped risk curve such that exceeding a lower limit actually increased risk of cardiovascular events, similar to having higher glucose control. As the old adage goes, ‘everything in moderation,’ including risk factor control.
– George Bakris, MD
Cardiology Today Editorial Board member