|For Safety, NHLBI Changes Intensive Blood Sugar
Treatment Strategy in Clinical Trial of Diabetes and Cardiovascular
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
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
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
ACCORD participants will continue to receive blood sugar treatment
from their study clinicians until the planned trial conclusion
in June 2009. Those participants in the intensive treatment group
will now be treated to the same A1C goals as those already in the
standard treatment group.
The intensive treatment group had a target blood sugar goal, measured
by hemoglobin A1C, of less than 6 percent. This is similar to blood
sugar levels in adults without diabetes. The standard treatment
group aimed for a target similar to what is achieved, on average,
by those with diabetes in the United States (A1C of 7 to 7.9 percent)
and lower than at study entry.
"The ACCORD findings are important, but will not change therapy
for most patients with type 2 diabetes. Few patients with high
cardiovascular risk like those studied in ACCORD are treated to
blood sugar levels as low as those tested in this study, " said
Judith Fradkin, M.D., director, Division of Diabetes, Endocrinology,
and Metabolic Diseases at the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK). "People with diabetes
should never adjust their treatment plan or goals without consulting
their health care providers."
In ACCORD, intensive treatment group participants achieved, on
average, A1C values lower than standard treatment group participants.
Half of the participants in the intensive treatment group achieved
an A1C of less than 6.4 percent, and half of the participants in
the standard treatment group achieved an A1C of less than 7.5 percent.
The average blood sugar levels for both groups were lower than
when they entered the study.
The ACCORD trial was designed to determine whether intensively
lowering blood sugar would reduce the risk of cardiovascular events
such as heart attack, stroke, or death from cardiovascular disease,
specifically in people with type 2 diabetes who are at particularly
high risk for a cardiovascular event. Prior studies suggested that
reducing blood sugar to levels found in non-diabetic adults may
reduce the rate of cardiovascular diseases among those with diabetes.
However, a randomized clinical trial was needed to determine whether
that hypothesis is accurate.
"ACCORD is an important study intended to find new answers
to help people with type 2 diabetes reduce their high risk of heart
disease," said Denise G. Simons-Morton, M.D., Ph.D., NHLBI
project officer for ACCORD and a member of the ACCORD steering
committee. "Hypotheses about treatments to prevent cardiovascular
disease in people with type 2 diabetes need to be tested in clinical
trials such as ACCORD. The ACCORD results, along with results from
other studies, will contribute to determining what the treatment
goals should be in patients with various characteristics."
Conducted at 77 sites nationwide and in Canada, the trial includes
adults between the ages of 40 and 82 at enrollment who, in addition
to type 2 diabetes, also have two or more other risk factors for
heart disease or had been diagnosed with heart disease before entering
the study. Thus, participants were included in the ACCORD trial
because they were at especially high risk — more risk than
is associated with diabetes alone — for having a heart attack,
stroke, or of dying from cardiovascular disease. Participants,
who on average had diabetes for 10 years at enrollment, were randomly
assigned to either standard (5,123 participants) or intensive (5,128)
blood sugar treatment goals. They were also enrolled in one of
two other ACCORD randomized clinical trials examining effects of
treatments for blood pressure or blood lipids; those study components
will continue. Participants had been followed for 2 years to 7
years at the time the intensive blood sugar control treatment was
These results from ACCORD do not apply to patients with type 1
(juvenile) diabetes, according to Fradkin. It is also unclear whether
the results apply to patients with recently diagnosed type 2 diabetes
or those whose cardiovascular risk is lower than the participants
studied in ACCORD.
Extensive analyses by ACCORD researchers have not determined a
specific cause for the increased deaths among the intensive treatment
group. Based on analyses conducted to date, there is no evidence
that any medication or combination of medications is responsible.
Most participants in the intensive treatment group achieved their
lower blood sugar goals with combinations of Food and Drug Administration-approved
diabetes medications. For both the intensive and standard treatment
groups, study clinicians could use all major classes of diabetes
medications available: metformin, thiazolidinediones (TZDs, primarily
rosiglitazone), insulins, sulfonylureas, exanatide, and acarbose.
"Because of the recent concerns with rosiglitazone, our extensive
analysis included a specific review to determine whether there
was any link between this particular medication and the increased
deaths. We found no link," said William T. Friedewald, M.D.,
ACCORD Steering Committee Chair and Clinical Professor of Medicine
and Public Health at Columbia University.
ACCORD researchers will continue to monitor participants and conduct
additional analyses to try and explain the findings. Investigators
are preparing a report of the findings for a peer-reviewed publication.
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.
To arrange an interview with an NHLBI spokesperson, please contact
the NHLBI Communications Office at (301) 496-4236 or email email@example.com.
To interview Dr. Friedewald on Wednesday, please contact NHLBI;
after February 6, contact Randee Sacks Levine at Columbia University
Office of Communications at 212-305-8044.
Part of the National Institutes of Health, the National Heart,
Lung, and Blood Institute (NHLBI) plans, conducts, and supports
research related to the causes, prevention, diagnosis, and treatment
of heart, blood vessel, lung, and blood diseases; and sleep disorders.
The Institute also administers national health education campaigns
on women and heart disease, healthy weight for children, and other
topics. NHLBI press releases and other materials are available
online at www.nhlbi.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
February 6, 2008 ACCORD News Conference press kit, http://www.nhlbi.nih.gov/health/prof/heart/other/accord/
National Diabetes Information Clearinghouse, http://diabetes.niddk.nih.gov/
National Diabetes Education Program http://ndep.nih.gov/
Your Guide to Living Well With Heart Disease, http://www.nhlbi.nih.gov/health/public/heart/other/your_guide/living_well.htm
ACCORD clinical trial website, http://www.accordtrial.org/public/index.cfm