Glucose lowering treatment in patients with coronary artery disease is prognostically important not only in established but also in newly detected diabetes mellitus: a report from the Euro Heart Survey on Diabetes and the Heart

Anselmino, Matteo; Öhrvik, John; Malmberg, Klas; Standl, Eberhard; Rydén, Lars

doi:10.1093/eurheartj/ehm519

Cited by 104 publications

(79 citation statements)

References 27 publications

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“…These findings are in agreement with results from registry studies and subgroup analyses of clinical trials that have raised concerns about the possibly harmful effects of exogenous insulin treatment in patients with CAD [3,13,14]. In the Euro Heart Survey on Diabetes and the Heart, insulin treatment was associated with roughly doubled adjusted 1 year mortality risk compared with oral glucose-lowering treatment [13]. An analysis of data from SCAAR showed a higher long-term mortality rate after first PCI in patients with diabetes compared with those without.…”

Section: Discussionsupporting

confidence: 88%

“…Despite this, combined treatment was even more strongly related to mortality after adjusting for confounders in comparison with diet or oral glucose-lowering treatment alone. These findings are in agreement with results from registry studies and subgroup analyses of clinical trials that have raised concerns about the possibly harmful effects of exogenous insulin treatment in patients with CAD [3,13,14]. In the Euro Heart Survey on Diabetes and the Heart, insulin treatment was associated with roughly doubled adjusted 1 year mortality risk compared with oral glucose-lowering treatment [13].…”

Section: Discussionsupporting

confidence: 86%

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Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

et al. 2012

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Aims/hypothesis The aim of this study was to analyse whether the increased mortality rates observed in insulintreated patients with type 2 diabetes and coronary artery disease are explained by comorbidities and complications. Methods A retrospective analysis of data from two Swedish registries of type 2 diabetic patients (n012,515) undergoing coronary angiography between the years 2001 and 2009 was conducted. The association between glucose-lowering treatment and long-term mortality was studied after extensive adjustment for cardiovascular-and diabetes-related confounders. Patients were classified into four groups, according to glucose-lowering treatment: diet alone; oral therapy alone; insulin in combination with oral therapy; and insulin alone.Results After a mean follow-up time of 4.14 years, absolute mortality rates for patients treated with diet alone, oral therapy alone, insulin in combination with oral therapy and insulin alone were 19.2%, 17.4%, 22.9% and 28.1%, respectively. Compared with diet alone, insulin in combination with oral therapy (HR 1.27; 95% CI 1.12, 1.43) and insulin alone (HR 1.62; 95% CI 1.44, 1.83) were associated with higher mortality rates. After adjustment for baseline differences, insulin in combination with oral glucoselowering treatment (HR 1.22; 95% CI 1.06, 1.40; p < 0.005) and treatment with insulin only (HR 1.17; 95% CI 1.02, 1.35; p<0.01) remained independent predictors for long-term mortality. Conclusions/interpretation Type 2 diabetes patients treated with insulin and undergoing coronary angiography have a higher long-term mortality risk after adjustment for measured confounders. Further research is needed to evaluate the optimal glucose-lowering treatment for these high-risk patients.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 86%

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

et al. 2012

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“…In contrast, there is some evidence that tight glycaemic control initiated soon after diagnosis of diabetes is associated with long-term reduction of risk of death and myocardial infarction [22][23][24], especially when combined with multifactorial risk factor management [25]. Observations in patients with myocardial infarction and newly detected glucose disturbances from the Euro Heart Survey on Diabetes and the Heart support this assumption [26]. The extended follow-up of DIGAMI 2 confirms the previous report on increased risk of [17] non-fatal myocardial infarction and stroke in patients on chronic insulin treatment.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin–Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study

et al. 2011

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Aims/hypothesis This post hoc analysis from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial reports on extended long-term outcome in relation to glucose-lowering agents in patients with myocardial infarction and type 2 diabetes. Methods Patients were randomised as follows: group 1, insulin-based treatment; group 2, insulin during hospitalisation followed by conventional glucose control; and group 3, conventional treatment. Treatment according to the above protocol lasted 2.1 years. Using the total DIGAMI 2 cohort as an epidemiological database, this study presents mortality rates in the randomised groups, and mortality and morbidity rates by glucose-lowering treatment during an extended period of follow-up (median 4.1 and max 8.1 years). Results Follow-up data were available in 1,145 of the 1,253 patients. The mortality rate was 31% (72% cardiovascular) without significant differences between treatment groups. The total number of fatal malignancies was 37, with a trend towards a higher risk in group 1. The HR for death from malignant disease, compared with group 2, was 1.77 (95% CI 0.87-3.61; p=0.11) and 3.60 (95% CI 1.24-10.50; p=0.02) compared with group 3. Insulin treatment was associated with non-fatal cardiovascular events (OR 1.89 95% CI 1.35-2.63; p=0.0002), but not with mortality (OR 1.30, 95% CI 0.93-1.81; p=0.13). Metformin was associated with a lower mortality rate (HR 0.65, 95% CI 0.47-0.90; p=0.01) and a lower risk of death from malignancies (HR 0.25, 95% CI 0.08-0.83; p=0.02). Conclusions/interpretation Patients with type 2 diabetes and myocardial infarction have a poor prognosis. Glucoselowering drugs appear to be of prognostic importance. Insulin may be associated with an increased risk of nonfatal cardiac events, while metformin seems to be protective against risk of death.

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“…Among the older adults of the Cardiovascular Health Study [19], a greater mortality rate was observed for those treated with insulin compared with those on oral hypoglycaemic agents, even though there was no apparent difference between these two subgroups in terms of fasting plasma glucose (~10 mmol/l). In the Euro Heart Survey, in diabetic patients with coronary artery disease, insulin was related to a more serious prognosis than were oral glucose-lowering medications [20]. Interestingly, in the VADT, insulin therapy at baseline was an independent predictor of subsequent CV mortality [8].…”

Section: Different Glucose Medications Different Outcomes?mentioning

confidence: 99%

Megatrials in type 2 diabetes. From excitement to frustration?

Prato

2009

Diabetologia

118

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Whether glycaemic control may result in a reduction of cardiovascular (CV) risk has been a matter of continuous discussion and investigation. Epidemiological analyses have extensively suggested a relationship between glycaemic control and CV events; however, the results of intervention trials have been less conclusive. The UKPDS reported a 16% reduction in the risk of myocardial infarction, but this reduction was not statistically significant. The results of the Kumamoto and PROactive studies could not allow any firm conclusions to be drawn either, because of limited size and the defined primary endpoint, respectively. The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trials and the Veteran Administration Diabetes Trial (VADT) were published in rapid succession over the second half of 2008 and at the beginning of 2009. A total number of almost 25,000 type 2 diabetic patients were recruited in these three trials, which assessed the effect of intensive glycaemic control vs conventional treatment on well-defined CV endpoints. In spite of the achievement and maintenance of strict glycaemic control (HbA 1c <7.0%), no beneficial effect of intensive therapy was apparent in any of the studies. At the same time these results were presented, the results of an analysis of the 10 year follow-up of the UKPDS also became available and provided a more optimistic view of the potential benefit of achieving good glycaemic control. The relative risk reductions for myocardial infarction and all-cause mortality were significantly lower in the patients who initially received the intensive treatment compared with those in the conventional treatment arm. Moreover, the initial benefit in terms of microvascular complications observed at the end of the intervention trial remained unaltered at follow-up. Once again the debate on the importance of glycaemic control in preventing macrovascular complications remains unsettled. These results, however, require some reconciliation, and the objective of this commentary is to analyse a series of elements, including the changes in the treatment approach to CV risk factors in type 2 diabetes, the effect of glucoselowering agents, and the characteristics of the patients included in the different trials, that should be taken into account when interpreting the results of intervention trials in type 2 diabetes.

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Glucose lowering treatment in patients with coronary artery disease is prognostically important not only in established but also in newly detected diabetes mellitus: a report from the Euro Heart Survey on Diabetes and the Heart

Abstract: Insulin therapy may relate to a more serious prognosis in CAD-patients with DM. There was a pronounced decrease in cardiovascular events in patients with newly detected DM prescribed GL drugs compared with those not receiving such treatment.

Cited by 104 publications

References 27 publications

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment

Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin–Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study

Megatrials in type 2 diabetes. From excitement to frustration?

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