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

[Guest guest]

Colleagues, the following is FYI and does not necessarily reflect my own

opinion. I have no further knowledge of the topic. If you do not wish to

receive these posts, set your email filter to filter out any messages

coming from @nutritionucanlivewith.com and the program will remove

anything coming from me.

---------------------------------------------------------

Public release date: 6-Jun-2008

http://www.eurekalert.org/pub_releases/2008-06/nhla-act060608.php

Contact: NHLBI Communications Office

NHLBI_news@...

NIH/National Heart, Lung and Blood Institute

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

Intensively targeting blood sugar to near-normal levels in adults with

type 2 diabetes at especially high risk for heart attack and stroke does

not significantly reduce the risk of major cardiovascular events, such

as fatal or nonfatal heart attacks or stroke, but increases risk of

death, compared to standard treatment. Researchers from the ACCORD

(Action to Control Cardiovascular Risk in Diabetes) clinical trial

compared a medical strategy aimed at near-normal blood sugar levels †"

below current recommendations -- to a strategy to reach more standard

blood sugar levels. Supported by the National Institutes of Health, the

study evaluated the effects of intensively targeting blood sugar control

among adults with established diabetes, high blood sugar levels, and

pre-existing heart disease or at least two cardiovascular disease risk

factors in addition to diabetes.

The first published results of the ACCORD trial of over 10,000

participants appear online in the New England Journal of Medicine (NEJM)

today and will be in the June 12 NEJM print edition. The results are

being presented at the American Diabetes Association's 68th Annual

Scientific Sessions in San Francisco on June 10.

In February, the NIH's National Heart, Lung, and Blood Institute (NHLBI)

stopped the intensive blood sugar strategy after an average of 3.5 years

of treatment, instead of the planned 5.6 years, due to safety concerns.

The intensive strategy group had a 22 percent higher risk of death †"

or 54 more deaths -- compared to the standard group. The increased risk

began emerging within 1 to 2 years after the strategy began to

aggressively lower the participants’ blood sugar levels. All

participants now follow a medical strategy to reach the standard blood

sugar levels while other components of the study continue.

" ACCORD is providing important evidence to help guide treatment

recommendations for adults with established type 2 diabetes who have had

a heart attack or stroke or who have two or more risk factors for

cardiovascular disease in addition to diabetes, " said NHLBI Director

G. Nabel, M.D. " For these individuals, intensively lowering

blood sugar to near-normal levels appears to be too risky. "

The researchers caution that the results might not apply to patients who

are at lower risk of cardiovascular disease than the ACCORD participants

or to patients with more recently diagnosed type 2 diabetes. On average,

ACCORD participants had been diagnosed with diabetes for 10 years at

enrollment.

ACCORD's ongoing studies of the effects of aggressively lowering blood

pressure and treating multiple blood lipids (cholesterol and

triglycerides) in high-risk diabetic patients are expected to continue

through June 2009.

" Adults with type 2 diabetes are two to four times more likely than

adults without diabetes to die from heart disease, so identifying the

safest and most effective ways to help them lower their risk of heart

disease, stroke, and death is critical, " Nabel noted. An estimated 21

million Americans have diabetes and 284,000 die from it each year.

Sixty-five percent of deaths in persons with diabetes are from

cardiovascular causes.

Conducted at 77 sites nationwide and in Canada, ACCORD randomly assigned

10,251 participants between the ages 40 and 79 (average age 62) to

standard or intensive blood sugar treatment goals. Therapy in both

groups included patient education and counseling, and treatment with any

of the major classes of Food and Drug Administration-approved diabetes

medications, as prescribed by their study clinician: metformin,

thiazolidinediones (TZDs, primarily rosiglitazone), insulins,

sulfonylureas, exanatide, and acarbose. Combinations of medications

could be used as needed to reach the treatment goals.

Hemoglobin A1C levels, a standard measure of average blood sugar levels

over the preceding two to three months, were used to monitor

participants' blood sugar. The standard strategy group (5,123

participants) aimed to lower blood sugar levels to an A1C of 7 to 7.9

percent †" a target similar to what is achieved, on average, by

individuals treated for type 2 diabetes in the United States. The

intensive strategy group (5,128 participants) had an A1C blood sugar

target of less than 6 percent †" similar to that found in adults

without diabetes. To join the study, participants needed to have an A1C

level of 7.5 percent or higher; at study enrollment, one-half of the

participants had an A1C level over 8.1 percent.

Half of the participants in the standard strategy group achieved an A1C

less than 7.5 percent, and half of the intensive strategy group achieved

an A1C less than 6.4 percent. On average, participants in both groups

achieved these levels within the first year of the study and maintained

them throughout the study.

After an average of 3.5 years, 257 people in the intensive strategy

group died, compared to 203 participants in the standard strategy group.

This difference of 54 deaths resulted in a 22 percent increased death

rate in the intensive group. Causes of death were similar in each group,

with about half from cardiovascular conditions, such as heart attack,

sudden cardiac death, stroke, or heart failure. However, the intensive

group had 41 more cardiovascular deaths than the standard group,

resulting in a 35 percent higher cardiovascular death rate.

" Despite detailed analyses, we have been unable to identify the precise

cause of the increased risk of death in the intensive blood sugar

strategy group, " noted lead author Hertzel C. Gerstein, M.D., M.Sc. " Our

analyses to date suggest that no specific medication or combination of

medications is responsible. We believe that some unidentified

combination of factors tied to the overall medical strategy is likely at

play. " Gerstein holds the Population Health Research Institute Chair in

Diabetes and is director of the Division of Endocrinology & Metabolism

and Diabetes Care and Research Program at McMaster University and

Hamilton Health Sciences, Hamilton, Canada.

To meet their more aggressive targets, participants in the intensive

group used more medications, were more likely to use combinations of

medications, and changed medications and/or doses of medications more

frequently than those in the standard group. For example, 52 percent of

participants in the intensive strategy group were on three oral

medications plus insulin compared with 16 percent of participants in the

standard strategy group. The intensive strategy was associated with more

adverse side effects from medications, hypoglycemia (low blood sugar)

events, weight gain, and fluid retention.

The researchers also studied whether participants' characteristics at

enrollment had an impact on their outcomes. They compared persons with

and without existing cardiovascular disease, women and men, those older

and younger than age 65, those with A1C levels lower and higher than 8

percent, and white and non-white participants. Death rates were

consistently higher in the intensive strategy group regardless of

baseline characteristics. However, compared to participants in the

standard group, those in the intensive group who began the study with no

history of heart attack or stroke, or with lower blood sugar levels (A1C

level 8 percent or less) had fewer combined cardiovascular events †"

fatal and nonfatal heart attacks or strokes †" during the study.

The increased risk of death from the intensive strategy surprised

researchers and other experts because earlier studies had shown that

blood sugar at near-normal levels was associated with lower

cardiovascular disease risk in people with type 2 diabetes. However,

these were observational studies, rather than randomized clinical

trials, as they did not test treatments to reduce blood sugar. In

addition, intensive blood sugar control has been shown in clinical

trials to reduce microvascular complications from diabetes †" including

eye, kidney, and nervous system diseases †" in people with type 1 or

type 2 diabetes, and to lower cardiovascular disease risk in people with

type 1 diabetes. However, the levels tested in other studies were not at

as low as the level targeted in the ACCORD intensive treatment group.

The American Diabetes Association's clinical guidelines recommend that

most people with type 2 diabetes reach and maintain an A1C of less than

7 percent. The guidelines also state that treatment should be

individualized. For example, a less stringent A1C goal should be

considered for people with severe or frequent low blood sugar or with

other medical conditions.

" The ACCORD results can now be considered when doctors are tailoring

blood sugar strategies for adults with type 2 diabetes who are at

especially high risk for cardiovascular disease, " said G.

Simons-Morton, M.D., Ph.D., a coauthor and NHLBI project officer for ACCORD.

Future analyses from ACCORD will determine the effects of the intensive

blood sugar strategy on microvascular diseases, cognition, quality of

life, and other outcomes in the study participants.

###

ACCORD is primarily funded by NHLBI, with additional funding and

scientific expertise contributed by the National Institute of Diabetes

and Digestive and Kidney Diseases. Other components of the NIH -- the

National Institute of Aging and National Eye Institute -- as well as the

Centers for Disease Control and Prevention, support substudies. The

following companies provided study medications, equipment, or supplies:

Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals

LP, Bayer HealthCare LLC, Closer Healthcare Inc., GlaxoKline

Pharmaceuticals, King Pharmaceuticals, Inc., Merck & Co., Inc., Novartis

Pharmaceuticals, Inc., Novo Nordisk, Inc., Omron Healthcare, Inc., and

Sanofi-Aventis U.S.

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.

Resources:

Questions and Answers About the ACCORD Clinical Trial,

http://www.nhlbi.nih.gov/health/prof/heart/other/accord/q_a.htm

February 6, 2008, ACCORD Blood Sugar Treatment Strategy Announcement,

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

--

ne Holden, MS, RD

" Ask the Parkinson Dietitian " http://www.parkinson.org/

" Eat well, stay well with Parkinson's disease "

" Parkinson's disease: Guidelines for Medical Nutrition Therapy "

http://www.nutritionucanlivewith.com/