The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped one treatment within a large, ongoing North American clinical trial of diabetes and cardiovascular disease 18 months early due to safety concerns after review of available data, although the study will continue.
In this trial of adults with type 2 diabetes at especially high risk for heart attack and stroke, the medical strategy to intensively lower blood glucose (sugar) below current recommendations increased the risk of death compared with a less-intensive standard treatment strategy. Study participants receiving intensive blood glucose lowering treatment will now receive the less-intensive standard treatment.
The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study enrolled 10,251 participants. Of these, 257 in the intensive treatment group have died, compared with 203 within the standard treatment group. This is a difference of 54 deaths, or 3 per 1,000 participants each year, over an average of almost four years of treatment. The death rates in both groups were lower than seen in similar populations in other studies.
"A thorough review of the data shows that the medical treatment strategy of intensively reducing blood sugar below current clinical guidelines causes harm in these especially high-risk patients with type 2 diabetes," said Elizabeth G. Nabel, M.D., director, NHLBI. "Though we have stopped this part of the trial, we will continue to care for these participants, who now will receive the less-intensive standard treatment. In addition, we will continue to monitor the health of all participants, seek the underlying causes for this finding, and carry on with other important research within ACCORD."
In stopping this part of the trial, Nabel accepted the recommendation of the 10-member Data and Safety Monitoring Board (DSMB)-an independent advisory group of experts in diabetes, cardiovascular disease, epidemiology, patient care, biostatistics, medical ethics, and clinical trial design that has been monitoring ACCORD since it began. A specific charge of any DSMB is to monitor participant safety.
An estimated 21 million Americans have diabetes and 284,000 die from it each year. Sixty-five percent of the deaths are related to cardiovascular causes. Type 2 diabetes increases the risk for heart disease 2 to 4 times.
The National Diabetes Education Program, a program of the NIDDK and the Centers for Disease Control and Prevention (CDC), promotes the diabetes care guidelines of the American Diabetes Association (ADA), which recommend an A1C goal of less than 7 percent for most people with type 2 diabetes. The ADA guidelines are based on established evidence that blood sugar control to this level reduces microvascular complications resulting from diabetes including eye, kidney, and nervous system diseases in people with type 1 or type 2 diabetes, and reduces cardiovascular disease in type 1 diabetes. The guidelines also state that treatment goals should be tailored to the individual. For example, a less stringent A1C goal should be considered for people with severe or frequent low blood sugar or with other medical conditions. These important ACCORD results can now be considered in addition to the guidelines when individualizing treatment.
NIDDK contributed funding and scientific expertise to ACCORD. The NIH's National Institute of Aging and National Eye Institute, as well as the CDC, are also contributing in order to conduct sub-studies in ACCORD. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca LP, Aventis Pharmaceuticals, Inc., Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Inc., MediSense Products (Division of Abbott Laboratories), Merck & Company, Inc., Novartis Pharmaceuticals, Inc., Novo Nordisk Pharmaceuticals, Inc., and Omron Healthcare, Inc.
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