Intensive Glycemic Control and Cardiovascular Outcomes: ACCORD
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study randomized 10,251 participants with either history of a CVD event or significant CVD risk to a strategy of intensive glycemic control (target A1C 6.0%) or standard glycemic control (A1C target 7.0-7.9%); investigators used multiple glycemic medications in both arms From a baseline median A1C of 8.1%, the intensive arm reached a median A1C of 6.4% within 12 months of randomization; the standard group reached a median A1C of 7.5% The glycemic control arm of ACCORD was halted early due to the finding of an increased rate of mortality in the intensive arm compared with the standard arm (1.41% vs. 1.14% per year; HR 1.22 [95% CI 1.01 to 1.46]); with a similar increase in cardiovascular deaths The primary outcome of ACCORD (MI, stroke, or cardiovascular death) was lower in the intensive glycemic control group, due to a reduction in nonfatal MI, but this reduction was not statistically significant when the study was terminated1 The potential cause of excess deaths in the intensive group of the ACCORD has been difficult to pinpoint. Exploratory analyses of the mortality findings of ACCORD (evaluating variables including weight gain, use of any specific drug or drug combination, and hypoglycemia) were reportedly unable to identify a clear explanation for the excess mortality in the intensive arm. The ACCORD investigators subsequently published additional analyses showing no increase in mortality in the intensive arm participants who achieved A1C levels7% or in those who lowered their A1C quickly after trial enrollment In fact, the converse was observed—those at highest risk for mortality were participants in the intensive arm with the highest A1C levels42References Gerstein HC, Miller ME, Byington RP, et al., for the Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-2559. Riddle MC, Ambrosius WT, Brillon DJ, et al, for the Action to Control Cardiovascular Risk in Diabetes Investigators. Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care 2010;33:983–990.