(Revised July 7, 2010)
Patients with type 2 diabetes mellitus die of cardiovascular disease (CVD) at rates two to four times higher than non-diabetic populations of similar demographic characteristics. They also experience increased rates of nonfatal myocardial infarction and stroke. With the growing prevalence of obesity in the United States, CVD associated with type 2 diabetes is expected to become an even greater public health challenge in the coming decades than it is now. Expected increases in event rates will be associated with a concomitant rise in suffering and resource utilization. Despite the importance of this health problem in the North American population, there is a lack of definitive data on the effects of intensive control of glycemia and other CVD risk factors on CVD event rates in diabetic patients.
The overall goal of the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) trial was to address this challenge by testing three complementary medical treatment strategies for type 2 diabetes to enhance the options for reducing the still very high rate of major CVD morbidity and mortality in this disease.
The design was a randomized, multicenter, double 2 X 2 factorial trial in 10,251 patients with type 2 diabetes mellitus. It was designed to test the effects on major CVD events of intensive glycemia control, of fibrate treatment to increase HDL-cholesterol and lower triglycerides (in the context of good LDL-C and glycemia control), and of intensive blood pressure control (in the context of good glycemia control), each compared to an appropriate control. All 10,251 participants were in an overarching glycemia trial. In addition, one 2 X 2 trial addressed the lipid question in 5,518 of the participants and the other 2 X 2 trial addressed the blood pressure question in 4,733 of the participants.
The glycemia trial was terminated early due to higher mortality in the intensive compared with the standard glycemia treatment strategies. The results were published in June 2008 (N Eng J Med
2008;358:2545-59). Study-delivered treatment for all ACCORD participants was stopped on June 30, 2009, and the participants were assisted as needed in transferring their care to a personal physician. The lipid and blood pressure results (as well as the microvascular outcomes and eye substudy results) were published in 2010. All participants are continuing to be followed in a non-treatment observational study.
The three specific primary ACCORD hypotheses were as follow. In middle-aged or older people with type 2 diabetes who are at high risk for having a cardiovascular disease (CVD) event because of existing clinical or subclinical CVD or CVD risk factors:
- does a therapeutic strategy that targets a HbA1c of < 6.0% reduce the rate of CVD events more than a strategy that targets a HbA1c of 7.0% to 7.9% (with the expectation of achieving a median level of 7.5%)
- in the context of good glycemic control, does a therapeutic strategy that uses a fibrate to raise HDL-C/lower triglyceride levels and uses a statin for treatment of LDL-C reduce the rate of CVD events compared to a strategy that only uses a statin for treatment of LDL-C
- In the context of good glycemic control, does a therapeutic strategy that targets a systolic blood pressure (SBP) of < 120 mm Hg reduce the rate of CVD events compared to a strategy that targets a SBP of < 140 mm Hg
The primary outcome measure for the trial was the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.
Secondary hypotheses included treatment differences in other cardiovascular outcomes, total mortality, microvascular outcomes, health-related quality of life, and cost-effectiveness.
Published ACCORD papers may be found here on this ACCORD homepage under ACCORD Publications
in the left hand bar. Under this link you will find:
- Details regarding the rationale, design, and conduct of ACCORD, published in the June 18, 2007 supplement to the American Journal of Cardiology (2007;99[suppl 12A]).
- Our primary glycemia results, published in 2008 in the New England Journal of Medicine (N Engl J Med 2008;358:2545-59).
- Our primary lipd trial results, published in 2010 in the New England Journal of Medicine (N Engl J Med 2010;362:1563-74).
- Our primary blood pressure trial results, published in 2010 in the New England Journal of Medicine (N Engl J Med 2010;362:1575-85).
- Our microvascular outcome results, published in 2010 in the Lancet (Online Lancet: June 29, 2010. DOI:10.1016/S0140-6736(10)60576-4).
- Our Eye Substudy results, published in 2010 in the New England Journal of Medicine (online N Eng J Med June 29, 2010 DOI 10.1056/NEJMoa1001288).