.
MEDICAL: DISEASES: DIABETES:
ACCORD Study: Cholesterol, BP Control Does Little Good for Diabetics
ACCORD Study: Cholesterol, BP Control Does Little Good for Diabetics
For Diabetes, Intensive Cholesterol and Blood Pressure Control Doesn't
Help Heart Risk
By CRYSTAL PHEND and PEGGY PECK
MedPage Today
March 14, 2010
ABC News
<http://abcnews.go.com/Health/DiabetesNews/
diabetes-intensive-cholesterol-blood-pressure-
control-heart-risk/story?id=10098023>
A shorter URL for the above link:
<http://tinyurl.com/yhsx9tv>
Research findings released today have dashed doctors' hopes that intensive
blood pressure and blood fat management could drive down diabetics' higher
risks of heart problems.
Results from the highly anticipated Action to Control Cardiovascular Risk
in Diabetes (ACCORD) trial proved once again that when it comes to
traditional measurements of heart disease risk, lower isn't always better.
Using a blood pressure target of 120 mm Hg rather than the general
population standard of 140 did not reduce nonfatal heart attacks, nonfatal
strokes or death from cardiovascular causes, reported Dr. William Cushman
of the VA Medical Center in Memphis, Tenn.
Likewise, adding the cholesterol-busting drug fenofibrate to standard
statin therapy did not reduce the chances of major adverse cardiovascular
events, according to Dr. Henry Ginsberg of Columbia University in New York
City.
Both studies, part of the complex ACCORD trial, were presented at the
American College of Cardiology meeting in Atlanta, Ga. and released
simultaneously online in the New England Journal of Medicine.
A third part of this research -- one which examined intensive lowering of
blood sugar to see if this had a positive effect -- was prematurely halted
in 2008 because it turned out that patients receiving this approach
actually had an increased, instead of decreased, risk of death.
------------------------------------
The complete article may be read at the URL above.
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
<http://www.nhlbi.nih.gov/health/prof/heart/other/accord/>
Questions and Answers about the ACCORD Trial Updated June 6, 2008
Effects of Intensive Glucose Lowering in Type 2 Diabetes Announcements
June 6, 2008
New Release: ACCORD Clinical Trial Publishes Results
A Therapeutic Strategy Targeting Blood Sugar to Near-Normal Levels Does
Not Reduce Cardiovascular Events But Increases Mortality in Persons with
Diabetes at High Risk
NEJM: Effects of Intensive Glucose Lowering in Type 2 Diabetes
NEJM Editorials and Perspective:
Intensive Glycemic Control in the ACCORD and ADVANCE Trials, Robert G.
Dluhy, M.D., and Graham T. McMahon, M.D., M.M.Sc.
Glycemic Targets and Cardiovascular Disease, William T. Cefalu, M.D.
Redefining Quality - Implications of Recent Clinical Trials, Harlan M.
Krumholz, M.D., and Thomas H. Lee, M.D.
ACCORD Blood Sugar Strategy Announcement February 6, 2008
Sample Letter To Participants
News Conference
News Release
Prepared Remarks, PDF file, 540 K
Elizabeth G. Nabel, MD
William T. Friedewald, MD
Hertzel C. Gerstein, MD, MSc FRCPC
Judith Fradkin, MD
The Full News Conference
Audio, WAV file, 56.7 MB
Transcript, PDF file, 132 K
ACCORD Study Web Site
List of ACCORD Clinical Center Networks and Network Sites
Questions and Answers
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
June 6, 2008
This page will be updated on March 15, 2010
<http://www.nhlbi.nih.gov/health/prof/heart/other/accord/q_a.htm>
Contents
What is the ACCORD Trial?
What is the status of the ACCORD study?
What is a Data and Safety Monitoring Board?
Why was the blood sugar treatment in the ACCORD trial changed?
What questions is the ACCORD trial seeking to answer?
How is the study designed?
Why was ACCORD studying intensive blood sugar lowering in patients with
type 2 diabetes?
Which drugs are used to lower blood sugar in ACCORD?
Why did more people in the intensive blood sugar treatment group die?
What were the causes of death in those assigned to intensive blood sugar
treatment compared to those in the standard blood sugar treatment group?
Were there any differences in outcomes in different types of people?
Did the ACCORD trial meet its treatment goals for blood sugar level?
Were there any benefits to the intensive blood sugar treatment?
What was the general level of medical treatment of the ACCORD
participants?
What adverse effects were seen from the intensive treatment?
What steps did the ACCORD study take to assure the safety of participants?
How has the ACCORD study changed as a result of this development?
Have ACCORD participants been notified of this information?
What do these results mean for people with type 2 diabetes?
What implications does this study have for people with type 1 diabetes?
What should clinicians who treat patients with diabetes do in light of
these findings?
What is the cost of the ACCORD study and how is it funded?
What implications does this finding have for future NIH-funded research in
diabetes?
Where can I find more information about the ACCORD trial?
Where can I find more information about diabetes and cardiovascular
disease?
What is the ACCORD Trial?
The ACCORD (Action to Control Cardiovascular Risk in Diabetes) Trial
(www.accordtrial.org ) is a large clinical study of adults with
established type 2 diabetes who are at especially high risk of
cardiovascular disease (CVD). Type 2 diabetes is a complex metabolic
disease characterized by high blood glucose (sugar) levels. People with
this form of diabetes have insulin resistance and a progressive loss of
the ability to produce insulin. Insulin is needed so that sugar in the
blood (which comes from eating food) can enter the cells of the body in
order for the body to function.
Type 2 diabetes increases the risk of a number of complications,
especially CVD, which is the leading cause of early death in people with
diabetes. Many people with diabetes are overweight and have high blood
pressure and lipid or cholesterol problems-conditions that further add to
their CVD risk. Adults with type 2 diabetes are two to four times more
likely to die of heart disease and stroke than adults without diabetes,
and about 65 percent of people with diabetes die from heart disease or
stroke.
The ACCORD Trial is testing three treatment approaches to determine the
best ways to decrease the high rate of major CVD events - heart attack,
stroke or death from CVD - among people with type 2 diabetes who are at
especially high risk of CVD. These treatment approaches are: intensive
lowering of blood sugar levels compared to a more standard blood sugar
treatment; intensive lowering of blood pressure compared to standard blood
pressure treatment; and treatment of blood lipids by a fibrate plus a
statin compared to a statin alone.
The study began enrolling participants in 2001 and is taking place in 77
clinical sites across the United States and Canada. A total of 10,251
adults with established type 2 diabetes are participating in the ACCORD
trial. At enrollment, study participants were between the ages 40 and 79
(average age 62), had diabetes for an average of 10 years, and were at
especially high risk for CVD events because they either already had
diagnosed CVD or they had at least two CVD risk factors in addition to
type 2 diabetes. The other CVD risk factors could be high cholesterol
(high low-density lipoprotein cholesterol, or LDL), high blood pressure,
smoking, or obesity.
ACCORD participant treatment is scheduled to end in 2009, and researchers
plan to report the final results in 2010.
What is the status of the ACCORD study?
The National Heart, Lung, and Blood Institute (NHLBI), which sponsors the
ACCORD trial, stopped the intensive blood sugar lowering strategy in the
study on February 6, 2008, and has transitioned participants in that
treatment group to the same treatment strategy as participants in the
standard group. NHLBI decided to make this change due to safety concerns
after a thorough review of the available data and a recommendation by the
study's Data and Safety Monitoring Board. The other two treatment
questions being examined in the study - the blood pressure and lipid
trials - will continue until June 2009 as planned.
Therefore, ACCORD participants are continuing to receive blood sugar
treatment from their study clinicians until the planned trial conclusion
in June 2009.
The results of intensive blood sugar lowering treatment strategy in the
ACCORD study are published by the New England Journal of Medicine online
June 6, 2008, and in the June 12, 2008, print edition. The results were
also presented June 10 at the American Diabetes Association's 68th Annual
Scientific Sessions in San Francisco.
What is a Data and Safety Monitoring Board?
The ACCORD Data and Safety Monitoring Board (DSMB) is an independent group
of 10 experts who regularly examine the study outcomes and safety data.
The ACCORD DSMB includes expertise in diabetes, cardiovascular disease,
statistics, ethics, epidemiology, and clinical trials. The DSMB is
responsible for providing recommendations concerning starting, continuing,
and/or stopping the clinical research study under review. The DSMB's
recommendations are based on safeguarding the interests of study
participants, assessing the safety and efficacy of study procedures, and
monitoring the overall conduct of the study.
Since the trial's onset in 2001, the ACCORD DSMB has met regularly,
generally every six months, to monitor study conduct and to review data
from ACCORD.
Why was the blood sugar treatment in the ACCORD trial changed?
In its regular review of the available study data, the ACCORD DSMB noticed
an unexpected increase in total deaths from any cause among participants
who had been randomly (by chance) assigned to the intensive blood sugar
strategy group compared to those assigned to the standard blood sugar
strategy group. The data analyses showed that over an average of 3.5 years
of treatment (ranging from about 2 years to about 7 years), 257
participants in the intensive group died, compared to 203 in the standard
group - a difference of 54 deaths, or an excess of about 3 deaths per
1,000 participants treated for a year. This translates to a statistically
significant 22% higher rate of death in the intensive than the standard
group.
There was a trend toward lower (10% lower) rate of primary outcome events,
primarily non-fatal heart attacks, in the intensive compared to the
standard treatment group. However, the DSMB recommended discontinuing
intensive blood sugar treatment because the harm of the intensive strategy
outweighs the potential benefit. NHLBI accepted the DSMB's recommendation
and decided to transition all participants to the standard blood sugar
strategy. This transition enables ACCORD to fulfill its commitment to
provide diabetes therapy to the participants until 2009, and, at the same
time, to enable the other two questions (blood pressure and lipids) to be
answered.
On the whole, the death rates in both blood sugar strategy groups were
lower than those seen in similar populations. That is, although the death
rate was higher in the intensive treatment group than the standard group,
it was still lower than death rates reported in other studies of type 2
diabetes. This difference is likely because ACCORD participants have
received and continue to receive excellent care for their diabetes, and
because participants in clinical trials generally have excellent adherence
to their treatment regimens.
What questions is the ACCORD trial seeking to answer?
The ACCORD trial was designed to determine if a strategy of intensive
lowering of blood sugar levels, intensive lowering of blood pressure, or
treatment of blood lipids with a fibrate plus a statin, can reduce the
risk of major CVD events in patients with type 2 diabetes who are at
especially high risk of CVD. Thus, the ACCORD trial was designed to answer
three complementary questions about treatment of people with diabetes.
The primary outcome measure for the trial is the first occurrence after
randomization of a major CVD event, specifically nonfatal heart attack,
nonfatal stroke, or CVD death. Secondary outcomes include total mortality
(deaths), microvascular outcomes (eg, eye, kidney, and nerve
complications), health-related quality of life, and cost-effectiveness.
Previous clinical trials in patients with type 2 diabetes have shown that
blood sugar lowering reduces eye, kidney, and nerve complications of
diabetes,
blood pressure lowering reduces CVD, eye, and kidney complications of
diabetes, and
LDL-cholesterol lowering with statins reduces CVD events, like heart
attacks and strokes.
However, no previous clinical trial has tested lowering blood sugar and
blood pressure to near-normal levels in patients with diabetes, and no
previous clinical trial has tested effects of treating multiple blood
lipids compared to treating only LDL-cholesterol in persons with diabetes.
How is the study designed?
After providing written informed consent, the participants were randomly
(i.e., by chance) assigned to intensive blood sugar-lowering strategy or
to standard blood sugar-lowering strategy. Blood sugar levels are measured
by a blood test called A1C, which reflects a person's average level of
blood sugar in the previous 2 to 3 months. Participants in ACCORD's
standard group were treated to a target A1C level of 7 to 7.9 percent,
which is about that achieved in the U.S. and lower than the participants'
levels when they joined the study. Therapy for those in the intensive
blood sugar group sought to achieve an A1C of less than 6 percent, a level
of blood sugar that is similar to that of a person without diabetes.
Participants were also asked to perform home blood glucose monitoring and
learned about preventing, recognizing, and treating hypoglycemia (very low
blood sugar). Hypoglycemic events were monitored carefully and, if
necessary, medications were adjusted to minimize severe hypoglycemic
reactions.
In addition to being randomized to one of the blood sugar strategy groups,
participants were also enrolled in one of two other randomized clinical
trials. One trial is comparing intensive lowering of blood pressure - to
near-normal levels - to standard blood pressure lowering. The other trial
is examining the effects of treating multiple blood lipids by using a
fibrate plus a statin - to raise HDL ("good") cholesterol, lower
triglyceride levels, and lower LDL ("bad") cholesterol - compared to a
statin to lower LDL cholesterol and a placebo that looks like the fibrate.
Why was ACCORD studying intensive blood sugar lowering in patients with
type 2 diabetes?
A large body of research in which adults were followed for several years
has shown that diabetes increases the risk of developing CVD. In addition,
the higher the blood sugar, the greater the future risk of CVD, and the
lower the blood sugar, the lower the risk of CVD. However, most studies
were "observational", rather than more rigorous randomized clinical trials
that test interventions or treatments, so they do not prove whether
lowering blood sugar levels reduces CVD risk. Although observational
studies are important to advancing our understanding of health and
disease, well-conducted randomized clinical trials are considered the gold
standard for determining safe and effective treatments.
Some clinical trials, however, have tested the effects of reducing blood
sugar through medical treatments. The United Kingdom Prospective Diabetes
Study (UKPDS), the NIH-supported Diabetes Control and Complications
Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC)
study, and other clinical trials have demonstrated benefits of lowering
blood sugar in persons with diabetes. Such studies have shown, for
example, that
For every percentage point drop in A1C blood test results (from 8.0
percent to 7.0 percent, for example), the risk of diabetic eye, nerve, and
kidney disease is reduced by 40 percent. Lowering blood sugar reduces
these microvascular complications in both type 1 and type 2 diabetes.
Intensive blood sugar control in people with type 1 diabetes (average A1C
of 7.4%) reduces the risk of any CVD event by 42 percent and the risk of
heart attack, stroke, or death from CVD by 57 percent (source: DCCT/EDIC,
reported in December 22, 2005, issue of the New England Journal of
Medicine.) Note: Although type 2 diabetes is similar to type 1 diabetes
(previously known as "juvenile" diabetes) in that both involve high blood
sugar levels due to inadequate insulin, the two forms of diabetes are
different in many ways, and results from studies in one type may not be
relevant to the other type.
In adults with more recent onset type 2 diabetes than the ACCORD
participants, the UKPDS showed a trend toward reduced CVD events,
particularly heart attacks. However, the results are not considered
conclusive.
Moreover, no previous major clinical trial has studied whether lowering a
raised blood sugar level to a level similar to that seen in people without
diabetes reduces the risk of CVD. In addition, no previous clinical trial
has studied the effects of intensive blood sugar lowering in people with
longstanding type 2 diabetes who already have CVD or have multiple risk
factors for CVD in addition to diabetes.
Which drugs are used to lower blood sugar in ACCORD?
All major classes of drugs approved by the FDA to treat diabetes were used
to treat blood sugar in both groups of the ACCORD blood sugar trial -
those in the intensive strategy group that targeted near-normal blood
sugar level as well as those in the standard blood sugar strategy group.
Specific medications used included (in order of frequency of use):
metformin; thiazolidinediones, or TZD's (rosiglitazone, pioglitazone);
injectable insulins; sulfonylureas (gliclazide, glimepiride, glipizide,
glyburide); and acarbose and exenatide. Combinations of medications could
be used to achieve the A1C goals.
The type, number and dosages of these drugs varied, depending on
participants' individual needs and their A1C goals. For example, metformin
was used in about 95% of intensive-group participants, and in about 87% of
standard group participants. Insulin was used in about 77% of
intensive-group participants, and in about 55% of standard-group
participants.
Participants in the intensive group were more likely to be on combinations
of drugs than participants in the standard group. For example, 52% of
participants in the intensive strategy group were on three oral
medications as well as insulin, compared to 16% of those in the standard
group.
For more information on diabetes medications, see
<http://diabetes.niddk.nih.gov/dm/pubs/medicines_ez/index.htm>
Why did more people in the intensive blood sugar treatment group die?
ACCORD researchers have extensively analyzed the available data and have
not been able to identify to date any specific cause for the higher death
rate among the intensive blood sugar treatment group. Based on analyses
done to date, there is no evidence that any medication or combination of
medications is responsible for the higher risk. In addition, although the
number of severe hypoglycemic events was greater in the intensive blood
sugar strategy group, this does not appear to account for the difference.
Because of the recent concerns with rosiglitazone (Avandia), which is one
of several medications used in ACCORD, researchers specifically reviewed
data to determine whether there was any link between this particular
medication and the increased deaths. To date, no link has been found.
For more on this issue, see
<http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=287>
ACCORD researchers will continue to monitor participants and conduct
additional analyses to try and explain the findings. However, the main
conclusion at this time is that the treatment strategy is responsible for
the findings, not any specific component of the strategy.
What were the causes of death in those assigned to intensive blood sugar
treatment compared to those in the standard blood sugar treatment group?
About half of the deaths were from cardiovascular diseases, such as heart
attack, sudden cardiac death, stroke, heart failure, or another
cardiovascular disease condition. Of the total 460 total deaths, there
were 229 deaths from cardiovascular causes - 135 in the intensive
treatment group and 94 in the standard treatment group. This difference
resulted in a significant 35 percent higher cardiovascular death rate in
the intensive strategy group. The remainder of the deaths was from other
causes such as cancer. Differences between the intensive and standard
treatment groups were present in overall death from any cause as well as
deaths from combined cardiovascular causes.
In addition, death rates were consistently higher in the intensive
strategy group regardless of participant characteristics at study
enrollment, such as whether the participants had existing cardiovascular
disease (versus multiple CVD risk factors), were male or female, were
older or younger than 65 years, had an A1C level lower or higher than 8
percent, or were of white or non-white race/ethnicity.
Were there any differences in outcomes in different types of people?
As noted above, participants' characteristics at enrollment did not impact
their risk of death from the intensive strategy. However, for the primary
outcome of any CVD event, including nonfatal events, there were some
differences. Participants who did not already have a CVD diagnosis (that
is, no history of heart attack or stroke) at enrollment were less likely
to have a cardiovascular event (fatal and nonfatal heart attacks or
strokes) if they were in the intensive group than if they were in the
standard group. A similar result was seen in participants who had lower
A1C levels at baseline (8.0% or lower). These findings, however, are only
suggestive and are not definitive.
Did the ACCORD trial meet its treatment goals for blood sugar level?
In general, intensive-group participants achieved lower blood sugar levels
than standard-group participants. An A1C level less than 6.4% was achieved
in half of the intensive-group participants and a level less than 7.5% in
half of the standard-group participants. These levels were maintained over
the average 3.5 year study period. The level achieved in the intensive
group required substantial effort on the part of ACCORD clinicians and
patients, including multiple medications, frequent clinic visits (at least
every 2 months), and frequent self-monitoring of blood sugar levels,
sometimes multiple times a day.
Were there any benefits to the intensive blood sugar treatment?
As noted above, analyses suggest that participants who were assigned to a
strategy of blood sugar lowering aiming for an A1C less than 6.0 percent
had a lower risk of a nonfatal heart attack.
However, it appears that, if a heart attack did occur, it may have been
more likely to have been fatal.
ACCORD investigators are analyzing the effects of this therapeutic
strategy on other serious health consequences of diabetes such as eye and
kidney diseases.
What was the general level of medical treatment of the ACCORD
participants?
The level of care was excellent. The average LDL-cholesterol (the "bad"
cholesterol) level was about 91 mg/dL in both groups, which is below the
recommended level of 100 mg/dL for people with diabetes. Their systolic
blood pressure was on average about 127 mm Hg, which is below the
recommended level of 130 mm Hg for diabetes patients. About three-quarters
were on aspirin, which is recommended to prevent heart attacks and
strokes. These values compare very favorably with the level of care in the
U.S. as a whole.
What adverse effects were seen from the intensive treatment?
There was a greater amount of seriously low blood sugar (called
hypoglycemia) events in the intensive group than in the standard group:
about 10% of intensive participants and about 3.5% of standard
participants had a hypoglycemia event that needed care from a medical
professional. There was more fluid retention in the intensive than the
standard group: 71% compared with 67%. About 28% of participants in the
intensive group gained more than 10 kg (22 pounds) of body weight,
compared with about 14% of participants in the standard group.
What steps did the ACCORD study take to assure the safety of participants?
Before launching the full-scale ACCORD trial, NHLBI funded a Vanguard
Phase of ACCORD to determine the safety and feasibility of implementing
the study protocol. The ACCORD Vanguard Phase treated and followed 1,174
participants for at least one year, with an average treatment duration of
about 1 and 1/2 years. There were no safety concerns identified in the
Vanguard Phase.
From the time ACCORD was launched, the DSMB monitored trial data regularly
(about every 6 months). Data on numerous safety parameters were collected
and reviewed, including serious adverse events, measures of liver and
kidney function, fluid retention, heart failure occurrence, and overall
mortality.
Participants visited study sites at least every 2 months for the intensive
group participants, and every 4 months for the standard group
participants. They learned about managing diabetes, self-monitoring their
blood sugar levels, and preventing and treating hypoglycemia (low blood
sugar) episodes. They were provided diabetes care and monitored for
hypoglycemia and heart failure. At these visits their health status was
reviewed, any side effects of medications were discussed, adjustments in
dosages were made, and medical tests were taken. They were provided
results of their tests and notified of any abnormal findings, so they
could take those results to their private physicians.
How has the ACCORD study changed as a result of this development?
The ACCORD study is continuing to treat all participants for their
diabetes; however, all participants are now being treated according to the
ACCORD protocol for standard blood sugar control. Participants formerly
randomized to the intensive blood sugar strategy have been transitioned to
the ACCORD standard blood sugar strategy, aiming for an A1C of 7 to 7.9
percent.
ACCORD will continue to study the effects of intensive compared with
standard treatment of blood pressure and the effects of fibrate plus
statin compared with placebo plus statin. All participants were randomized
at enrollment to one of these trials, but not both, in addition to being
randomized in the blood-sugar trial.
ACCORD will also continue to compare outcomes in the participants who were
in the intensive blood sugar treatment group with those in the standard
treatment group to determine whether the differences found to date persist
with time.
As is standard in clinical trials, ACCORD participants have the option to
stop volunteering for the study at any time.
Have ACCORD participants been notified of this information?
As soon as the NHLBI made the decision to stop the intensive blood sugar
lowering strategy, the Institute and the ACCORD Coordinating Center
implemented an action plan to alert all ACCORD investigators, staff, and
participants, as well as the public. All study participants were sent a
letter explaining that those in the more intensive blood sugar treatment
group would be transitioned to the ACCORD standard treatment strategy due
to safety concerns.
NHLBI also alerted the Food and Drug Administration, NIH institutes that
co-fund the trial, and the Centers for Disease Control and Prevention
(CDC). The investigators alerted their institution's Institutional Review
Boards. In addition, companies that donate medications, supplies, or
equipment were notified.
What do these results mean for people with type 2 diabetes?
Patients with type 2 diabetes should not be alarmed by these findings of
the ACCORD trial. Most individuals with type 2 diabetes who are similar to
the participants in ACCORD are not being treated to the very low goal of
the ACCORD intensive treatment group. This goal of less than 6 percent A1C
is very hard to reach for most patients who have had diabetes for several
years, often requiring multiple medications. Even the achieved level of
A1C of about 6.4% is often difficult to achieve in such patients. The
ACCORD participants were at particularly high risk of a CVD event or
already had CVD at enrollment, and the results may not apply to patients
who are not like the ACCORD participants.
Current guidelines for diabetes treatment recommend maintaining an A1C
level of less than 7 percent for most people with type 2 diabetes, based
on the proven benefits of blood sugar control in preventing eye, kidney,
and nerve diseases. However, treatment should be tailored to the
individual patient.
As always, patients with diabetes should not make any treatment changes
without first consulting with their physician.
All people with diabetes are at increased risk for cardiovascular
diseases, such as heart attack and stroke. Adopting a heart-healthy
lifestyle has been proven to help prevent diabetes and improve diabetes
control. Weight loss through a healthy diet and increased physical
activity helps prevent or delay type 2 diabetes, and a heart-healthy
lifestyle can improve diabetes control, lower blood pressure and
cholesterol, and reduce the risk of CVD. Controlling elevated blood
pressure and blood cholesterol have been proven to reduce the risk of CVD
in persons with diabetes.
What implications does this study have for people with type 1 diabetes?
These results also do not apply to patients with type 1 diabetes.
The risk of heart disease is about 10 times higher in people with type 1
diabetes than in those without diabetes. The NIH-funded Diabetes Control
and Complications Trial (DCCT) in type 1 diabetes patients showed that
intensive blood sugar control aimed at a near-normal A1C level reduced
complications of the eyes, nerves, and kidneys. In 2005, the long-term
follow-up of DCCT participants showed that intensive blood sugar control
also lowers by about half the risk of heart disease and stroke in people
with type 1 diabetes. These results strongly suggest that patients with
type 1 diabetes should begin intensive blood sugar control as early as
possible. This recommendation has not changed. For young people without
complications, the guidelines recommend an A1C goal as close to normal as
possible without significant hypoglycemia.
It should be noted that participants in the DCCT received intensive
treatment early in the course of disease and before the onset of CVD.
Researchers have not studied the risks and benefits of intensive therapy
in type 1 diabetes patients with established CVD.
What should clinicians who treat patients with diabetes do in light of
these findings?
The National Diabetes Education Program (NDEP), sponsored by the NIH and
the CDC, promotes the American Diabetes Association's guidelines for
diabetes care. Under these guidelines, the A1C goal for most patients with
type 2 diabetes is less than 7 percent, with treatment tailored to
individual needs. For example, the guidelines state: "Less stringent A1C
goals may be appropriate for patients with a history of severe
hypoglycemia, patients with limited life expectancies, children,
individuals with comorbid conditions, and those with longstanding diabetes
and minimal or stable microvascular complications."
Individualization of treatment can now take into account the important
findings from the ACCORD trial. Based on the ACCORD findings, the
increased risk of death may outweigh the benefits from medical-treatment
strategies aiming to achieve blood sugar control at levels that are near
those who do not have diabetes (A1C to less than 6 percent) among patients
with established CVD or who are otherwise at especially high risk of CVD
(two or more risk factors in addition to diabetes).
These results may not apply to patients with type 2 diabetes who are
younger, who have less-established diabetes, or who have a lower risk of
CVD than participants studied in the ACCORD trial. It is not known what
effect more intensive therapy might have on CVD in younger people with
type 2 diabetes or in patients with a lower risk of CVD than were studied
in the ACCORD trial.
Other clinical trials in type 2 diabetes, such as the ADVANCE (Action in
Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled
Evaluation) international trial and the VADT (Veterans Administration
Diabetes Trial), have recently reported their findings. The findings from
ACCORD will be taken together with findings from these and other studies
to help determine appropriate evidence-based treatment approaches for
people with diabetes.
Return to "Contents"
What is the cost of the ACCORD study and how is it funded?
The total cost of the trial is about $300 million. The NHLBI sponsors the
study and funds the sites through contracts and inter-agency agreements.
Other components of the NIH, including the National Institute of Diabetes
and Digestive and Kidney Diseases, the National Institute on Aging, and
the National Eye Institute contribute funding. The CDC funds sub-studies
within ACCORD on cost-effectiveness and health-related quality of life.
The following companies provided study medications, equipment, or
supplies: Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca
Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare Inc.,
GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Inc., Merck &
Company, Inc., Novartis Pharmaceuticals, Inc., Novo Nordisk
Pharmaceuticals, Inc., Omron Healthcare, Inc., and Sanofi-Aventis U.S.
What implications does this finding have for future NIH-funded research in
diabetes?
This finding reinforces the importance of large randomized, controlled
clinical trials for determining optimal treatment for diabetes and other
diseases and for determining effective interventions for preventing CVD.
There are still unanswered questions about optimal blood sugar control, as
well as many other questions about how best to treat diabetes to prevent
its medical complications. The NIH will consult with experts in diabetes
and its complications to determine the most compelling opportunities for
further research to improve the treatment of diabetes.
The ACCORD Blood Pressure and Lipid trials are continuing because of the
very important questions these two components are testing.
Where can I find more information about the ACCORD trial?
For more information about ACCORD, visit www.accordtrial.org/ or visit
http://www.nhlbi.nih.gov and click on "Clinical Trials," then ACCORD.
Where can I find more information about diabetes and cardiovascular
disease?
For information about the prevention, diagnosis, and treatment of
diabetes, see the websites of the National Diabetes Information
Clearinghouse http://diabetes.niddk.nih.gov/ and the National Diabetes
Education Program http://ndep.nih.gov/ . For information about the
prevention, diagnosis, and treatment of cardiovascular disease, see
http://www.nhlbi.nih.gov.
Volume 358:2545-2559 June 12, 2008 Number 24
Effects of Intensive Glucose Lowering in Type 2 Diabetes
The Action to Control Cardiovascular Risk in Diabetes Study Group
New England Journal of Medicine
<http://content.nejm.org/cgi/content/full/NEJMoa0802743>
Action to Control Cardiovascular Risk in Diabetes (ACCORD)
This study is ongoing, but not recruiting participants.
First Received: October 27, 1999 Last Updated: December 4, 2009
<http://clinicaltrials.gov/ct/show/NCT00000620>
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Collaborators: National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK)
National Institute on Aging (NIA)
National Eye Institute (NEI)
Centers for Disease Control and Prevention
Information provided by: National Heart, Lung, and Blood Institute
(NHLBI)
ClinicalTrials.gov Identifier: NCT00000620
The purpose of this study is to prevent major cardiovascular events (heart
attack, stroke, or cardiovascular death) in adults with type 2 diabetes
mellitus using intensive glycemic control, intensive blood pressure
control, and multiple lipid management.
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial: Design
and Methods
The American Journal of Cardiology
Volume 99, Issue 12, Pages S21-S33
J. Buse
Volume 29, Issue 5, Pages 756-761 (September 2008)
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial and
Hurricane Katrina: Lessons for managing clinical trials during and after a
natural disaster
Roberta McDuffiea, John Summersonb, Patricia Reillya, Caroline Blackwellb,
David Goffb, Angela R. Kimelb, Lenore Cragob, Vivian Fonsecaa
Received 11 March 2008; accepted 30 May 2008. published online 04 July
2008.
Contemporary Clinical Trials
Volume 99, Issue 12, Supplement, Pages S21-S33 (18 June 2007)
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial: Design
and Methods
The ACCORD Study Group
John B. Buse, MD, PhD
The American Journal of Cardiology
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study
Solicitation Number: NIH-NHLBI-HC-15A-10-07
Agency: Department of Health and Human Services
Office: National Institutes of Health
Location: National Heart, Lung and Blood Institute, Rockledge Dr.
Bethesda, MD
<https://www.fbo.gov/index?s=opportunity&mode=form&id=
223368aaf066fccb48f5125563312bd1&tab=core&_cview=0>
A shorter URL for the above link:
<http://tinyurl.com/yzkpdrb>
Trial Summary
Title: Action to Control Cardiovascular Risk in Diabetes Blood Pressure
Trial (ACCORD BP)
Trial Sponsor: National Heart, Lung, and Blood Institute
Year Presented: 2010
Year Published 2010
Topic(s): General Cardiology, Noninvasive Cardiology
Summary Posted: 3/14/2010 8:00:00 AM
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
<http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=1911>
Google Scholar
<http://scholar.google.com/scholar?hl=en&rlz=1T4DAUS_enUS314US314&q=
%22Action%20to%20Control%20Cardiovascular%20Risk%20in%20Diabetes%
22&um=1&ie=UTF-8&sa=N&tab=ws>
A shorter URL for the above link:
<http://tinyurl.com/yhjgut3>
Content Sample:
Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design
and Find Full-Text @ TU
JB Buse - The American Journal of Cardiology, 2007 - Elsevier
Most patients with type 2 diabetes mellitus develop cardiovascular disease
(CVD), with substantial
loss of life expectancy. Nonfatal CVD contributes greatly to excess
healthcare costs and decreased
quality of life in patients with diabetes. The current epidemic of obesity
has raised ...
Cited by 68 - Related articles
of the lipid trial protocol of the Action to Control Cardiovascular Risk
in Diabetes ( Find Full-Text @ TU
HN Ginsberg, DE Bonds, LC Lovato, JR Crouse - The American Journal of ,
2007 - Elsevier
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial
aims to test whether
a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus
a fibrate is more efficacious
in reducing cardiovascular events than a statin plus placebo in patients
with type 2 ...
Cited by 44 - Related articles - All 2 versions
treatment strategies in the Action to Control Cardiovascular Risk in
Diabetes ( Find Full-Text @ TU
HC Gerstein, MC Riddle, DM Kendall, RM - The American Journal of , 2007 -
Elsevier
There is an independent progressive epidemiologic relation between
glycemia and cardiovascular
disease (CVD) events; however, whether lowering glucose levels with
currently available therapies
can reduce CVD events remains unknown. The Action to Control
Cardiovascular Risk in ...
Cited by 43 - Related articles - All 2 versions
Medical management of hyperglycaemia in type 2 diabetes mellitus: a
consensus cardiobarbanza.com [PDF]
Find Full-Text @ TU
DM Nathan, JB Buse, MB Davidson, E Ferrannini, RR - Diabetologia, 2009 -
Springer
... Abbreviations ACCORD Action to Control Cardiovascular Risk in Diabetes
ADVANCE Action
in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled
Evaluation CVD
cardiovascular disease Diabetologia (2009) 52:1730 DOI
10.1007/s00125-008-1157-y ...
Cited by 1145 - Related articles - BL Direct - All 92 versions
The action to control cardiovascular risk in diabetes memory in diabetes
study ( Find Full-Text @ TU
JD Williamson, ME Miller, RN Bryan, RM Lazar, - The American Journal of ,
2007 - Elsevier
Type 2 diabetes mellitus and cognitive impairment are 2 of the most common
chronic conditions
found in persons aged =60 years. Clinical studies have shown a greater
prevalence of global
cognitive impairment, incidence of cognitive decline, and incidence of
Alzheimer disease ...
Cited by 26 - Related articles - All 2 versions
pressure intervention of the Action to Control Cardiovascular Risk in
Diabetes ( Find Full-Text @ TU
WC Cushman, RH Grimm, JA Cutler, GW Evans - The American Journal of ,
2007 - Elsevier
The Action to Control Cardiovascular Disease in Diabetes (ACCORD) blood
pressure trial is
an unmasked, open-label, randomized trial with a sample size of 4,733
participants. This report
describes the rationale, design, and methods of the blood pressure
interventions in ...
Cited by 29 - Related articles - All 2 versions
knowledge and rationale for the Action to Control Cardiovascular Risk in
Diabetes Find Full-Text @ TU
DC Goff, HC Gerstein, HN Ginsberg, WC - The American Journal of , 2007 -
Elsevier
Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD)
at rates 24 times
higher than patients without diabetes but with similar demographic
characteristics. The prevalence
of diabetes is increasing in the United States and, thus, the prevention
of CVD in patients ...
Cited by 31 - Related articles - All 2 versions
Intensive glycemic control in the ACCORD and ADVANCE trialsutas.edu.au
[PDF]
Find Full-Text @ TU
RG Dluhy, GT McMahon - New England Journal of Medicine, 2008 -
content.nejm.org
... 6 Two studies in this issue of the Journal the ACCORD (Action to
Control Cardiovascular Risk
in Diabetes) trial 7 (ClinicalTrials.gov number, NCT00000620) and the
ADVANCE (Action in Di-
abetes and Vascular Disease: Preterax and Dia- micron Modified Release ...
Cited by 105 - Related articles - All 7 versions
Glucose control and vascular complications in veterans with type 2
diabetesFind Full-Text @ TU
W Duckworth, C Abraira, T Moritz, D Reda, - England Journal of , 2008 -
content.nejm.org
... studies, the Action in Diabetes and Vascular Disease: Preterax and
Diamicron Modified Release
Controlled Evaluation (ADVANCE) trial (ClinicalTrials.gov number,
NCT00145925
[ClinicalTrials.gov] ) 9 and the Action to Control Cardiovascular Risk in
Diabetes (ACCORD) trial ...
Cited by 325 - Related articles - All 21 versions
Glycemic control and coronary heart disease risk in persons with and
without Find Full-Text @ TU
E Selvin, J Coresh, SH Golden, FL - Archives of Internal , 2005 -
archinte.highwire.org
... The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial
of approximately 10 000
adults with diabetes, scheduled to be published in 2010, should provide a
definitive answer to
the question of the efficacy of glucose-lowering treatments in the
prevention of ...
Cited by 100 - Related articles - BL Direct - All 4 versions
Primary prevention of cardiovascular diseases in people with diabetes
mellitus: a ahajournals.org [HTML]
Find Full-Text @ TU
JB Buse, HN Ginsberg, GL Bakris, NG Clark, F Costa, - Circulation, 2007 -
Am Heart Assoc
... 130 mm Hg. 8,44 The ACCORD (Action to Control Cardiovascular Risk in
Diabetes)
blood pressure study 45 will explicitly test the cardiovascular efficacy
of lowering the
systolic blood pressure below 140 mm Hg. It has randomized ...
Cited by 274 - Related articles - All 25 versions
[HTML] The burden of treatment failure in type 2
diabetesdiabetesjournals.org [HTML]
Find Full-Text @ TU
JB Brown, GA Nichols, A Perry - Diabetes Care, 2004 - Am Diabetes Assoc
... 7.0% or lower. An even stronger signal would be provided by a
treatment threshold
of 6.0%, which has proved widely achievable in the test phase of the
Action to Control
Cardiovascular Risk in Diabetes (ACCORD) study (12). ...
Cited by 171 - Related articles - BL Direct - All 7 versions
Cardiovascular disease in diabetes mellitus type 2: a potential role for
novel
JM Hayden, PD Reaven - Current opinion in lipidology, 2000 -
journals.lww.com
Advertisement. Current Opinion in Lipidology. Wolters Kluwer Health Logo.
All Issues. ...
Cited by 87 - Related articles - BL Direct - All 5 versions
The effect of interventions to prevent cardiovascular disease in patients
with type 2 Find Full-Text @ TU
ES Huang, JB Meigs, DE Singer - The American journal of medicine, 2001 -
Elsevier
Cited by 149 - Related articles - BL Direct - All 12 versions
Improvements in diabetes processes of care and intermediate outcomes:
United annals.org [HTML]
Find Full-Text @ TU
JB Saaddine, B Cadwell, EW Gregg, MM - Annals of internal , 2006 - Am
Coll Physicians
... N Engl J Med. 1999;341:410-8. [PMID: 10438259].[Abstract/Free Full
Text]. 48. Action
to Control Cardiovascular Risk in Diabetes (ACCORD). Accessed at
http://www.accordtrial.
org on 30 November 2005. 49. Grant RW, Buse JB, Meigs JB. ...
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Glycemic control and macrovascular disease in types 1 and 2 diabetes
mellitus: Find Full-Text @ TU
C Stettler, S Allemann, P Ji, CA Cull, RR - American Heart , 2006 -
Elsevier
Cited by 175 - Related articles - All 13 versions
Additive effects of glycaemia and blood pressure exposure on risk of
complications Find Full-Text @ TU
IM Stratton, CA Cull, AI Adler, DR Matthews, HAW Neil, - Diabetologia,
2006 - Springer
Page 1. Diabetologia (2006) 49: 17611769 DOI 10.1007/s00125-006-0297-1
ARTICLE IM
Stratton . CA Cull . AI Adler . DR Matthews . HAW Neil . RR Holman
Additive effects of glycaemia
and blood pressure exposure on risk of complications in type 2 diabetes: a
prospective ...
Cited by 107 - Related articles - BL Direct - All 15 versions
[CITATION] and rationale for the Action to Control Cardiovascular Risk in
Diabetes Find Full-Text @ TU
DC Goff Jr, HC Gerstein, HN Ginsberg, WC Cushman, - Am J Cardiol, 2007
Cited by 11 - Related articles
[CITATION] for the Action to Control Cardiovascular Risk in Diabetes Study
GroupFind Full-Text @ TU
HC Gerstein, ME Miller, RP Byington, DC Goff Jr, JT - N Engl J Med, 2008
Cited by 12 - Related articles
Glycemic targets and cardiovascular diseaseFind Full-Text @ TU
WT Cefalu - New England Journal of Medicine, 2008 - content.nejm.org
... In this issue of the Journal, results are presented from two recently
completed multicenter clinical
trials, the ACCORD (Action to Control Cardiovascular Risk in Diabetes)
trial (ClinicalTrials.gov
number, NCT00000620 [ClinicalTrials.gov] ) 4 and the ADVANCE (Action in
Diabetes ...
Cited by 34 - Related articles - BL Direct - All 5 versions
<snip>
--------------------------------------
WEBBIB0910
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Temple University
(215) 204 - 4584
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