Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial

Abstract

Objective: To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

Research design and methods: ACCORD enrolled 10,251 type 2 diabetes patients aged 40-79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A1c goals of <6.0% (<42 mmol/mol; intensive glycemia) or 7.0-7.9% (53-63 mmol/mol; standard glycemia) and then randomized a second time to either 1) systolic BP goals of <120 mmHg (intensive BP) or <140 mmHg (standard BP) or 2) simvastatin plus fenofibrate (intensive lipid) or simvastatin plus placebo (standard lipid). Proportional hazards models were used to assess combinations of treatment assignments on the composite primary (deaths due to CVD, nonfatal myocardial infarction [MI], and nonfatal stroke) and secondary outcomes.

Results: In the BP trial, risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50-0.91), BP (HR 0.74; 95% CI 0.55-1.00), or both (HR 0.71; 95% CI 0.52-0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02-1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group.

Conclusions: In the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality.

Trial registration: ClinicalTrials.gov NCT00000620.

Figure 1

Five-year event rates, HR, and corresponding 95% CI for comparisons of the three more intensively treated groups to the standard BP-lowering/standard glucose-lowering treatment group in the ACCORD BP trial. P values are for pairwise comparisons of more intensively treated groups with the standard/standard group. BP, blood pressure; Gly, glycemia; std, standard; int, intensive; macrovasc, macrovascular end point; microvasc, microvascular end point.

Figure 2

Five-year event rates, HR, and corresponding 95% CI for comparisons of the three more intensively treated groups to the fibrate placebo/standard glucose-lowering treatment group in the ACCORD lipid trial. P values are for pairwise comparisons of more intensively treated groups with the standard (placebo)/standard group. Gly, glycemia; Lip, lipid; std, standard; int, intensive; macrovasc, macrovascular end point; microvasc, microvascular end point.