Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

Abstract

Objective: To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality.

Research design and methods: Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics.

Results: There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.95, 95% CI 1.41-2.69) versus no history of neuropathy (0.99, 0.79-1.26; P value for interaction 0.0008), higher A1C (A1C >8.5%: HR 1.64, 95% CI 1.22-2.22; A1C 7.5-8.4%: 1.00, 0.75-1.34; A1C <7.5%: 1.00, 0.67-1.50; P value for interaction 0.04), and aspirin use (HR 1.45, 95% CI 1.13-1.85, compared with 0.96, 0.72-1.27, in nonusers; P value for interaction 0.03).

Conclusions: We found a remarkable similarity of effect from intensive compared with standard glycemia treatment on mortality across most baseline subgroups. No differential effect was found in subgroups defined by variables anticipated to have an interaction: age, duration of diabetes, and previous history of cardiovascular disease. The three baseline characteristics that defined subgroups for which there was a differential effect on mortality may help identify patients with type 2 diabetes at higher risk of mortality from intensive regimens for glycemic control. Further research is warranted.

Figure 1

Demographic characteristics and medical history. HRs are shown for all-cause mortality in intensive versus standard glycemia groups within demographic and medical history subgroups, adjusted for the study stratification factors: 1) history of CVD (except for the analysis of CVD variables), 2) assignment to the Lipid or Blood Pressure trial (each trial had different eligibility criteria), 3) assignment to Lipid trial and randomized to fenofibrate, and 4) assignment to the Blood Pressure trial and randomized to the intensive blood pressure intervention.

Figure 2

Medication and laboratory tests. HRs are shown for all-cause mortality in intensive versus standard glycemia groups within the medication and laboratory tests subgroups adjusted for the study stratification factors: 1) history of CVD (except for the analysis of CVD variables), 2) assignment to the Lipid or Blood Pressure trial (each trial had different eligibility criteria), 3) assignment to Lipid trial and randomized to fenofibrate, and 4) assignment to the Blood Pressure trial and randomized to the intensive blood pressure intervention.

Figure 3

A1C and all-cause mortality. Spline curves displaying the log of the HR for all-cause mortality by treatment and baseline A1C are shown. All HRs are with respect to standard glycemia with baseline A1C of 7.0. The bold line represents the intensive treatment group, the finer line the standard group, and the colored lines the 95% CIs.