“ ACCORD,” Action to Control Cardiovascular Risk in Diabetes   Abstract     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. Despite the importance of this health problem in North America, there are few definitive data that could illuminate the possibility of reducing CVD event rates in diabetic patients by intensive glycemic control, and by control of other CVD risk factors.     The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial compares three complementary medical treatment strategies for type 2 diabetes, to determine if one strategy or another reduces the rate of major CVD morbidity and mortality associated with this disease. Trial participants are 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:     The design is a double 2 X 2 factorial design, in which the first factor is usual vs. intensive glycemic control, and the second factor is either cholesterol control (UC vs SI), or BP control (UC vs. SI). Details of the three possible factors are:     1. Glycemia controlled using usual care targets vs. intensive care targets. The UC target attempts to control HbA1c at 7.0% to 7.9% (with the expectation of achieving a median level of 7.5%. The SI target attempts to control HbA1c at <6.0%.     2a. Cholesterol lowering is achieved using a statin to reduce LDLc plus: a. A fibrate to raise HDLc and lower triglycerides, or b. Placebo     2b. Blood pressure is controlled using Usual Care targets vs. Intensive Care targets. The UC target attempts to control SBP at < 140 mmHg; the SI target attempts to control SBP at <120 mmHg.     All participants will randomized into the glycemia-control trial. Of these, 5,800 will also be randomized into the cholesterol lowering trial, while 4,200 will be randomized into the BP lowering trial. Thus, ACCORD is conducted as two 2x2 factorial trials simultaneously.     The primary outcome is the first occurrence of a major cardiovascular disease event, specifically nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Secondary hypotheses include treatment differences in other cardiovascular outcomes, total mortality, microvascular outcomes, health-related quality of life, and cost-effectiveness.     The 10,000 participants will be treated and followed for 4 to 8 years (approximate mean of 5.6 years) at approximately 60 clinical sites administratively located within 7 Clinical Center Networks in the United States and Canada. Recruitment occurs during two non-contiguous periods: an initial period that began in January 2001 for the Vanguard Phase of the trial (during which 1184 participants were randomized) and then a subsequent period beginning in January 2003 and ending in June 2005. Follow-up is scheduled to end in June 2009, with the primary results announced in early 2010.