William Friedewald, M.D.
Clinical Professor of Public Health and Medicine, Columbia University
Chairman, ACCORD Steering Committee

Thank you. As Dr. Nabel has just described, ACCORD first began recruiting participants in 2001. We have been treating and following our study participants for an average of about 4 years, ranging individually from 2 to 7 years.

At the same time that we began to observe the troubling mortality differences described by Dr. Nabel, we were also noticing a slight trend toward beneficial effects of the intensive blood-sugar lowering. The primary outcome for the study is a combination of heart attacks, stroke and cardiovascular death, and we were seeing about 10 percent fewer nonfatal cardiovascular events such as heart attacks in the intensive treatment group compared to the standard treatment group. However, it appeared that, if a heart attack did occur, it was more likely to be fatal. In addition, the intensive treatment group had more unexpected sudden deaths, even without a clear heart attack.

The ACCORD researchers undertook extensive analyses to try and understand potential causes of the mortality difference. Our analyses have not identified, to date, any specific cause for the increased deaths among the intensive treatment group. However, the magnitude of the difference in the death rate, with only a small improvement in nonfatal events, indicated that, in the interest of safety of the participants, the intensive blood-sugar treatment part of the ACCORD study should be changed and all participants treated according to the standard blood-sugar group.

As we examined the data, we sought to identify any drugs -- or combinations of drugs -- that might explain this higher mortality rate in our intensively treated group. However, with our analyses so far we have not been able to find conclusive evidence that any medication or combination of medications is responsible for the increased risk.

Because of the recent concerns raised with regard to rosiglitazone, also known as Avandia, one of the drugs we use in ACCORD, we specifically analyzed the data to try and determine whether there was any link between this particular medication and the increased deaths we were seeing in the ACCORD intensive treatment group. At this time, we have found no link, and thus the use of rosiglitazone does not seem to explain the increased mortality.

Based on other studies, it is possible that the intensive blood-sugar lowering therapy benefits patients in other ways, such as by lowering the risk of other complications of diabetes, such as eye and kidney diseases. We will continue to analyze all of the effects of the intensive treatment group based on the data gathered to date and on future assessments of the participants in the intensive group, even though they will now be treated to standard blood-sugar lowering goals.

In addition to actively monitoring ACCORD participants, we will conduct additional analyses to try and explain the findings. Meanwhile, we are preparing a report of our current findings for publication in a peer-reviewed medical journal in the near future.

In a moment, Dr. Gerstein will provide more details on how the blood-sugar treatment part of the study was conducted and how ACCORD will continue over the next 18 months.

Before I close, I want to reiterate Dr. Nabel's comments and assure everyone, especially our study volunteers, that our first priority is to the safety of our participants. On Monday, our 77 clinical centers across the U.S. and Canada sent letters to each study participant explaining this important finding and describing the changes in the ACCORD study. For the participants in the standard treatment group, their care will continue without changes. Participants in the intensive treatment group will be transitioned to the standard treatment after consulting with their ACCORD clinician. They will be called by their study doctor in the next few days so they can discuss without delay any concerns or questions they might have.

Although the ACCORD findings are extremely important, most individuals with type 2 diabetes are not treated to blood sugar levels as low as those tested in the intensive treatment group in the study. In addition, these results only apply to patients like the ACCORD participants, who were selected to have cardiovascular disease or two additional risk factors for cardiovascular disease, in addition to diabetes. To reach the levels of blood sugar achieved by our intensive group required consistent hard work on the part of these participants, with frequent blood sugar monitoring, multiple medications, and frequent contact with our ACCORD clinical staff diabetes experts.

However, for this special group of individuals with diabetes, as exemplified in the ACCORD population, which were average age of 62, had diabetes for an average of 10 years, and had know heart disease or were at high risk, less stringent A1C goals are likely appropriate, with an aim for around 7%. No one with diabetes should change their treatment without consulting with their healthcare professional first.

Finally, I would like to reiterate that even with the higher death rate in our intensive group compared to our standard group, this death rate is still lower than that seen in similar populations in other studies, and it is lower among individuals with type 2 diabetes in the general community.

I would like to now turn to my colleague, Dr. Hertzel Gerstein, who leads the ACCORD clinical center network in Canada and the ACCORD blood-sugar working group. Hertzel will describe the blood-sugar treatments used in the ACCORD trial.

Last updated: February 6, 2008