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14-01-2010 | Cardiology | Article

New ACCORD analyses focus on severe symptomatic hypoglycemia



MedWire News: Two new analyses offer insights into the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which was stopped after an interim analysis detected increased mortality among patients assigned to intensive compared with standard glucose control.

The post-hoc analyses, published in the British Medical Journal, identify baseline subgroups at increased risk for severe hypoglycemia, but also eliminate this complication as an explanation for the mortality difference between the treatment groups.

The ACCORD trial was designed to test the hypothesis that aggressive control of glycemia – with blood glucose concentrations reduced to near-normal levels – would reduce the rate of nonfatal and fatal cardiovascular (CV) disease in high-risk individuals.

The study enrolled 10,251 adults with Type 2 diabetes, a glycated hemoglobin (HbA1c) concentration of 7.5% or more, and aged 40–79 years with established CV disease, or aged 55–79 years with evidence of subclinical disease, albuminuria, left ventricular hypertrophy or two CV risk factors. They were randomized using a 2x2 factorial design to standard or intensive glucose control, with HbA1c targets of 7.0–7.9% and less than 6%, respectively.

The trial was stopped early because of higher mortality in the intensive-control group: 1.42 deaths per 100 person–years compared with 1.14 per 100 person–years in the standard treatment group (hazard ratio[HR]=1.22). The intensive-control group also exhibited significantly higher CV mortality and did not have a lower incidence of major CV events compared with patients in the standard-treatment arm.

In the first of the new analyses, Michael Miller (Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA) and team performed a multivariate analysis to identify determinants of severe symptomatic hypoglycemia.

Risks for this complication were significantly increased in women, African Americans, those with lower education levels, older participants, and those who used insulin at study entry. Interestingly, larger reductions in HbA1c at 4 months were not associated with an increased risk for hypoglycemia; conversely, the risk rose with each 1% increase in average HbA1c.

“These observations can provide guidance to clinicians who attempt to intensify patient therapy and adjust glycemic treatment goals on the basis of individual risk,” Miller et al conclude.

“Future studies should be directed at developing strategies to reduce severe hypoglycemia in high-risk groups.”

In the second analysis, Denise Bonds (National Institutes of Health, Bethesda, Maryland, USA) and colleagues tested whether there was a link between hypoglycemia and mortality among study participants.

In both treatment groups, patients who had one or more episodes of severe hypoglycemia had higher mortality than those without any episodes, at adjusted HRs of 1.41 in the intensive and 2.30 in the standard treatment group.

However, among participants who experienced at least one episode of severe hypoglycemia, the risk for death was actually lower in the intensive versus the standard treatment arm, at an adjusted HR of 0.55.

“Although hypoglycemia cannot be excluded as a possible contributor to death in some of the fatal cases, the increased relative risk of mortality observed in the intensive treatment group in the ACCORD trial cannot be explained by severe hypoglycemia,” Bonds and co-authors conclude.

“Susceptibility to severe hypoglycemia may be a marker for an underlying disorder that increases the risk for death in patients with diabetes, even when glycemia is controlled according to current guidelines.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Joanna Lyford


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