ArticlesEffects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial
Introduction
People with type 2 diabetes have a two to three times higher incidence of ischaemic heart disease than people without diabetes, even when other risk factors are taken into account.1, 2 Reasons for this difference are unclear. Diabetes, however, is defined on the basis of raised glucose concentrations.3 As the incidence of ischaemic heart disease increases with increasing glycated haemoglobin A1c (HbA1c) concentrations,4 glucose concentrations might be an important contributing factor. This possibility is supported by the finding that 10 years of intensive compared with standard glucose-lowering therapy reduces the 20-year risk of myocardial infarction by 15% in people with newly diagnosed type 2 diabetes.5 Additionally, a meta-analysis of four large trials showed 15% reduced incidence of total myocardial infarction (95% CI 6–24) during a mean follow-up period of 4·4 years.6
The ACCORD trial was a large North American trial of intense versus standard glucose-lowering therapy in people with established type 2 diabetes and additional risk factors for cardiovascular disease. As previously reported the intervention had a non-significant effect on the primary composite cardiovascular outcome. The incidence of non-fatal myocardial infarction, however, was decreased, whereas the risk of death, particularly from cardiovascular causes, was increased. The effect on cardiovascular mortality remains unexplained. Exploratory analyses have so far identified no relation with severe hypoglycaemia,7 the degree or speed of glucose lowering,8 or other potential factors.9, 10, 11 The reduced rate of ischaemic heart disease in ACCORD was not explored. Here we report the effects of the ACCORD glucose-lowering interventions on indices of ischaemic heart disease, including fatal and non-fatal myocardial infarction and unstable and new-onset angina, and the degree to which change in HbA1c concentration accounts for any of these effects.
Section snippets
Design
The design and results of the ACCORD trial have been published previously.12, 13 Briefly, 10 251 men and women aged 40–79 years with established type 2 diabetes (mean duration 10 years), a mean gHbA1c concentration of 67 mmol/mol (8·3%), and either previous cardiovascular events or risk factors for cardiovascular disease were recruited from 77 clinical centres in the USA and Canada. Participants were randomly allocated to either intensive glucose-lowering therapy, with a target HbA1c
Results
No significant differences were seen between groups for baseline characteristics, or for blood pressure, LDL cholesterol and creatinine concentrations, or use of cardiovascular drugs during follow-up (table). Patients were followed up for a mean of 3·7 years until the date of transition, and a mean of 4·8 years until the end of full follow-up. Greater numbers of all classes of glucose-lowering drugs and combinations had been used in the intensive treatment group than in the standard group at
Discussion
Intensive therapy was associated with significant reductions in the 5-year incidence of ischaemic heart disease (13%), any myocardial infarction (16%), non-fatal myocardial infarction (19%), coronary revascularisation (16%), and unstable angina (19%). These analyses were not prespecified in the ACCORD protocol, but our findings are consistent with those from other large outcomes trials where intensive glucose-lowering therapy reduced the incidence of fatal and non-fatal myocardial infarction in
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2020, Obesity MedicineCitation Excerpt :The traditional prevention and treatment of CVDs in patients with T2DM often adopts comprehensive individualized treatment strategies clinically, which includes control blood glucose and comprehensively regulate various cardiovascular risk factors. However, the results of traditional hypoglycemic agents have been rather disappointing (Hayward et al., 2015; Gerstein et al., 2014). Studies have shown that traditional anti-diabetic drugs can reduce the risk of microvascular events including neuropathy, diabetic nephropathy and retinopathy by controlling glucose, but are generally failed to show significant reduction in the risk of macrovascular events (myocardial infarction and stroke for instance) (Hayward et al., 2015; Gerstein et al., 2014).