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Foos et al, EASD, Lisbon, 13 September 2011 Comparison of ACCORD trial outcomes with outcomes estimated from modelled and meta- analysis studies Volker.

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Presentation on theme: "Foos et al, EASD, Lisbon, 13 September 2011 Comparison of ACCORD trial outcomes with outcomes estimated from modelled and meta- analysis studies Volker."— Presentation transcript:

1 Foos et al, EASD, Lisbon, 13 September 2011 Comparison of ACCORD trial outcomes with outcomes estimated from modelled and meta- analysis studies Volker Foos 1, Adam Lloyd 2, Nick Freemantle 3, David Grant 2, William Herman 4. 1 IMS Health, Basel, Switzerland, 2 IMS Health, London, UK, 3 University College London, London, UK, 4 University of Michigan, Ann Arbor, MI, USA EASD ORAL PRESENTATION– 13th September 2011 Session: OP 01 Assessing cardiovascular risk Presentation number: 3

2 2 The ACCORD trial reported higher mortality in type 2 diabetes patients treated with intensive glycemic control The ACCORD trial 1 −Randomized controlled study including patients −Purpose to investigate whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. Treatment Targets: Intensive glycemic control: HbA1c < 6% Standard Treatment:HbA1c between 7% and 7.9% Background 1 Effects of Intensive Glucose Lowering in Type 2 Diabetes, The Action to Control Cardiovascular Risk in Diabetes Study Group, N Engl J Med June 2008

3 3 Background Findings after 3.5 years of follow up All cause mortality was found to be increased in the intensified treatment arm with an hazard ratio of 1.22 Hypoglycemia as well as weight gain was increased with intensive treatment major cardiovascular events were not significantly reduced The ACCORD trial findings in detail Foos et al, EASD, Lisbon, 13 September 2011

4 4 Findings of the ACCORD trial contradict with earlier landmark studies Results of ACCORD suggest that intensive glucose lowering in high- risk patients with type 2 poses a harm that was not recognized to this stage. These findings contradict with earlier landmark investigations such as the UKPDS (T2D) and the DCCT/EDIC (T1D) which have shown that intensive blood glucose control can substantially lower the risk of diabetes complications and reduce the long-term risk of developing cardiovascular disease. Although the effects were found to be significant, the underlying causes for the increased mortality rates are yet not fully understood and a debate has started about the reasons for the these findings and their implications to current treatment guidelines. Background Foos et al, EASD, Lisbon, 13 September 2011

5 5 The purpose of this investigation was to put the ACCORD findings into context by comparing them to outcomes of other data sources To compare ACCORD findings to a recently conducted random effects meta-analysis including data from ACCCORD, ADVANCE and VADT To compare ACCORD findings to etimates of a well established and validated computer simulation model for type 2 diabetes (IMS CORE Diabetes Model) Modelling approach −Cardiovascular risk scores were calculated on the basis of UKPDS data 2 −Two distinct approaches were compared Materials and methods 2 A model to estimate the lifetime health outcomes of patients with Type 2 diabetes: the UKPDS Outcomes Model (UKPDS no. 68), P. M. Clarke et al., Diabetologia (2004) Standard approach – Continuous and unlimited risk decrease for glucose lowering Modified approach – HbA1c related CV risk reductions were limited to values > 7%

6 6 Comparison of end points End Points (RR) Non fatal MI Non fatal stroke Heart failure All cause mortality ACCORD Meta Analysis Model 1 Restriction of additional risk decrease below 7% Model 2 No Restriction of additional risk decrease Materials and methods Foos et al, EASD, Lisbon, 13 September 2011 Relative risk scores for intensified versus standard treatment were compared for the below listed end points:

7 7 The random effects Meta Analysis included data from the ACCORD, ADVANCE and VADT trials All cause mortality (Odds ratios and 95% CI) Foos et al, EASD, Lisbon, 13 September 2011 Results

8 8 The random effects Meta Analysis included data from the ACCORD, ADVANCE and VADT trials Myocardial Infarction (Odds ratios and 95% CI) Foos et al, EASD, Lisbon, 13 September 2011 Results

9 9 The random effects Meta Analysis included data from the ACCORD, ADVANCE and VADT trials Stroke (Odds ratios and 95% CI) Foos et al, EASD, Lisbon, 13 September 2011 Results

10 10 The random effects Meta Analysis included data from the ACCORD, ADVANCE and VADT trials Heart Failure (Odds ratios and 95% CI) Foos et al, EASD, Lisbon, 13 September 2011 Results

11 11 Comparison of CVD endpoints and mortality – ACCORD vs. meta-analysis and model projections Results MI Stroke HF All cause death Foos et al, EASD, Lisbon, 13 September 2011 Confidence intervals from ACCORD trial RR of all cause mortalty for intensively treated patients in ACCORD was significantly higher than model projections Model predictions for non fatal MI, non fatal stroke and heart failure did lie within the 95% CIs derived from ACCORD.

12 12 Comparison of CVD endpoints and mortality – ACCORD vs. meta-analysis and model projections Results MI Stroke HF All cause death Foos et al, EASD, Lisbon, 13 September 2011 Confidence intervals from pooled estimates Adjusting the model so continuing to reduce Hba1c below 7% causes no further reduction in CV risk brought the model estimates closer to ACCORD findings. Model outcomes fell within confidence intervals predicted by the meta- analysis for all events.

13 13 Findings of the ACCORD trial contradict with earlier landmark studies Relative risk of all cause mortality in ACCORD was significantly different from that modelled based on previous data. This difference −was not seen in other endpoints, −was not consistent across recent studies, −and was not fully explained by hypothesising a lower limit of 7% for HbA1c benefit. Observed mortality effects in the ACCORD trial may be related to factors other than glucose lowering. Conclusion Foos et al, EASD, Lisbon, 13 September 2011

14 14 Thank You! Foos et al, EASD, Lisbon, 13 September 2011


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