Among 10,251 study participants, the 5128 treated to achieve a target glycated haemoglobin (HbA1c) level below 42 mmol/mol (6.0%) were 20% less likely to have a fatal or non-fatal myocardial infarction during the average 3.7 years of active treatment than the 5123 treated to achieve a standard HbA1c level of 53 to 63 mmol/mol (7.0–7.9%).

And this reduced risk was maintained over an additional 1.2 years of follow-up after intensive treatment was replaced with standard treatment.

The findings were similar for non-fatal myocardial infarction alone and the composite ischaemic heart disease outcomes of myocardial infarction, unstable angina or coronary revascularisation, and any myocardial infarction or unstable angina, with intensive glucose lowering reducing the risks by 22%, 11% and 21%, respectively.

The researchers, led by Hertzel Gerstein (McMaster University and Hamilton Health Sciences, Ontario, Canada), found that adjusting for the HbA1c concentrations achieved before treatment transition rendered the effects nonsignificant.

This “supports the hypothesis that the degree of glucose lowering or some closely related factor accounts for the effect of the intervention on ischaemic heart disease”, they report in The Lancet.

Together with evidence of raised glucose concentrations and increased cardiovascular risk in people with genetic markers of hyperglycaemia, the findings suggests that “rising glucose concentration is a modifiable risk factor for ischaemic heart disease”, they add.

Although intensive glucose had a beneficial effect on ischaemic heart disease, the researchers note that the results do not negate the ACCORD findings of an increased risk of death from cardiovascular disease with intensive versus standard glucose lowering and are at odds with the observation that intensive glucose lowering did not reduce the risk of fatal myocardial infarction alone.

As most of the deaths occurred in patients whose HbA1c concentrations did not decrease from baseline, the team suggests that persistent but failed attempts to lower glucose concentrations in these individuals may have been harmful.

In a related comment, Jean-Louis Chiasson and Jacques Le Lorier, from the University of Montreal in Quebec, Canada, agree that further assessment of the risks and benefits of intensive glucose-lowering treatment is required.

“In the meantime it is probably wise to aim for a target HbA1c concentration of less than 64 mmol/mol (8.0%) in patients older than 65 years with comorbidities”, they recommend.

From www.medwirenews.com

Abstract

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

Prof Hertzel C Gerstein MD a , Prof Michael E Miller PhD b, Prof Faramarz Ismail-Beigi MD c, Joe Largay PA-C d, Charlotte McDonald MD e, Heather A Lochnan MD f, Gillian L Booth MD g, for the ACCORD Study Group

Summary

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.

Nyhetsinfo

www red DiabetologNytt