ACCORD and Risk-Factor Control in Type 2 Diabetes.

Patients with type 2 diabetes mellitus without a history of myocardial infarction have the same risk of a coronary event as patients without diabetes who do have a history of myocardial infarction.1 This observation was part of the basis for the recommendation by the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program that diabetes should be considered a “coronary heart disease risk equivalent” and a target for aggressive reduction of risk factors.2 It has also contributed to the rationale for randomized clinical trials to evaluate the effects of risk-factor reduction in such high-risk patients. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (ClinicalTrials.gov number, NCT00000620) was one of the landmark trials to evaluate the overall effects of drug intervention in patients with type 2 diabetes.3 In comparison with two other, related trials, the United Kingdom Prospective Diabetes Study (UKPDS; Current Controlled Trials number, ISRCTN75451837)4 and the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (NCT00145925),5 the ACCORD study included not only intervention groups aiming for control of hyperglycemia and hypertension but also one for control of hyperlipidemia. A previous study by the ACCORD investigators concluded that a strategy of intensified glycemic control was associated with an increased risk of death.6 However, a recent meta-analysis did not confirm such an increase in risk,7 and the role of intensified glycemic control has been a subject of debate. In this issue of the Journal, the joint publication of the ACCORD blood pressure trial (ACCORD BP)8 and the ACCORD lipid trial (ACCORD Lipid),9 although not resolving this issue, makes the picture of diabetes management more complete. In the ACCORD BP study, investigators evaluated the potential benefits of targeting a systolic blood-pressure level below 120 mm Hg versus a level below 140 mm Hg in patients with type 2 diabetes (34% of whom had cardiovascular disease).8 After 4.7 years, there was no significant between-group difference in the annual rate of the primary outcome, a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. Serious adverse events that were attributed to blood-pressure medication were more frequent in the intensive-therapy group. Owing to the factorial design of the overall ACCORD study and the inclusion and exclusion criteria that were applied, the study’s statistical power was reduced, and the event rate was lower than expected. It thus remains a possibility that a larger trial or one in a higher-risk population might have shown a significant benefit. A beneficial effect was shown for the secondary end point of total stroke. However, the number of major coronary disease events was far higher than the number of total strokes (253 vs. 36 in the intensive-therapy group and 270 vs. 62 in the standard-therapy group). Thus, the main conclusion to draw from this study must be that a systolic blood-pressure target below 120 mm Hg in patients with type 2 diabetes is not justified by the evidence. Unfortunately, the design and results of the ACCORD BP study leave unresolved the issue of the optimal blood-pressure target in patients with diabetes. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,