Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial

Abstract

Background: Hyperglycaemia could substantially increase the risk of ischaemic heart disease in patients with type 2 diabetes. We investigated whether intensive lowering of glucose concentrations affects risk.

Methods: We assessed 10,251 adults aged 40-79 years with established type 2 diabetes, mean glycated haemoglobin A1c (HbA1c) concentration of 67 mmol/mol (8·3%), and risk factors for ischaemic heart disease enrolled in the ACCORD trial. Participants were assigned to intensive or standard therapy (target HbA1c less than 42 or 53-63 mmol/mol [less than 6·0% or 7·0-7·9%], respectively). We assessed fatal or non-fatal myocardial infarction, coronary revascularisation, unstable angina, and new angina during active treatment (mean 3·7 years) plus a further mean 1·2 years. This trial is registered with ClinicalTrials.gov, number NCT00000620.

Findings: Myocardial infarction was less frequent in the intensive than in the standard therapy group during active treatment (hazard ratio [HR] 0·80, 95% CI 0·67-0·96; p=0·015) and overall (0·84, 0·72-0·97; p=0·02). Findings were similar for combined myocardial infarction, coronary revascularisation, and unstable angina (active treatment HR 0·89, 95% CI 0·79-0·99, overall 0·87 0·79-0·96) and for coronary revascularisation alone (0·84, 0·75-0·94) and unstable angina alone (0·81, 0·67-0·97) during full follow-up. With lowest achieved HbA1C concentrations included as a time-dependent covariate, all hazards became non-significant.

Interpretation: Raised glucose concentration is a modifiable risk factor for ischaemic heart disease in middle-aged people with type 2 diabetes and other cardiovascular risk factors.

Funding: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Eye Intitute, and Centers for Disease Control and Prevention.

Figure 1. Ischemic Heart Disease Incidence and Hazard Ratios

Forest Plot of Incidence and Hazard Ratios. The number of events, annual incidence (%/year), hazard ratios with 95% confidence intervals and P values are show for each treatment group from baseline until the end of the intervention trial (i.e. pre-transition), and from baseline until the end of the ACCORD trial (i.e. active plus additional follow-up). All analyses use the intent-to-treat approach, include the initial occurrence of each listed event, and account for competing risks due to deaths. Unstable angina includes new-onset angina, accelerated angina or rest angina. The numbers of the composite outcome of any MI or unstable angina shown in the figure differ from those in a prior report due to a typographic error; the numbers in the prior report referred to non-stroke CV death, or nonfatal MI or unstable angina.

Figure 2

Event Curves. The incidence of events in the intensive and standard glycemia groups from the time of randomization until the transition date (accounting for competing risk due to death) and until the end of the ACCORD trial is shown.

Figure 3. Ischemic Heart Disease Incidence and Hazard Ratios After Adjustment for Pre-transition A1c Levels

Forest Plot and Hazard Ratios Adjusted for Pre-transition A1c Levels. Hazard ratios adjusted for the pre-transition A1c levels as a time-varying covariate and account for competing risk due to death.