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Late Breaking Trials on Risk factors and Diabetes: William B WHITE (Farmington, US):

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ESC Congress 2013 31 August – 4 September Amsterdam, Netherlands:

Examination of cardiovascular outcomes with a log lipton versus standard of care in patients with type 2 diabetes mellitus and acute coronary syndrome thank you dr. harold and dr. bannerman its pleasure to be here in amsterdam this morning at this press conference i’m going to be presenting the objectives and end points of examine which was one of the recent studies

Ruling out cardiovascular risk and a population of high-risk patients with type 2 diabetes mellitus with one of the new drugs for the treatment of diabetes alig lipton a dpp-4 inhibitor the primary objective of examined was to demonstrate that major cardiovascular events are not higher with the drug compared to placebo in type 2 patients with a recent acute coronary

Syndrome who are also receiving the standard of care for diabetes as well as for secondary cardiovascular prevention around the globe the primary endpoint of the study was the composite of the first occurrence of cardiovascular death non-fatal myocardial infarction and non-fatal stroke if non-inferiority had been achieved at the time of the appropriate evaluation

Then superiority assessment would occur in a hierarchy of statistical analysis that would have tried to attempt to evaluate without we demonstrated a reduction in cardiovascular events on alig lipton versus placebo a pre-specified secondary endpoint was the primary endpoint including an additional component which was urgent revascularization due to unstable angina

And then major endpoints bed were also evaluated were cardiovascular death and that included those that were part of the primary endpoint and those occurring subsequent to a non-fatal primary endpoint and all-cause mortality order the patients in the study or those with type 2 diabetes receiving any hyperglycemic therapy either alone or combination with other drugs

They had to have had a 2 coronary syndrome within 15 to 90 days of randomization and that was defined as an acute myocardial infarction or hospitalization for unstable angina with very strict criteria they also received local standard of care for type 2 diabetes and secondary prevention with the exclusion of other dpp-4 inhibitors or glp-1 agonist since they would

Have confounding mechanisms of action patients with unstable cardiovascular conditions are those on dialysis within 14 days of planned randomization were also excluded from the trial this is the sort of a snapshot of the primary finding of this trial non-inferiority was met for all the endpoints if you look at the figure at the bottom here one point three is the

Mark of non inferiority as defined by this trial as well as by our regulatory agency the food and drug administration that the upper bound had to be less than that and for the primary endpoint of surely met that with a point estimate of point nine six in an upper bound of 1.16 with 621 major adverse cardiovascular events in the trial the secondary endpoint likewise

With the inclusion of urgent revascularization for unstable angina i had a point estimate of point 95 with an upper bound of 1.1 for all cardiovascular deaths now are being shown as a ninety-five percent confidence or evolved all cardiovascular death was had a point estimate of point eight five with an upper bounds of 1.10 and all-cause mortality point eight eight

With an upper bound of one point oh eight to summarize all major findings from this trial the rates of major cardiovascular events for similar with a low clifton compared to placebo in patients with type 2 diabetes in recent acute coronary syndrome this observation occurred in the following context significantly lower hemoglobin a1c levels also known as glycated

Hemoglobin of 0.36 percent and that was persistent during the course of the study median duration 18 months but up to 40 months of treatment a high overall rivalz for event rate of eleven percent for the primary endpoint with a median follow-up of 18 months and a high level of standard of care for both diabetes and for secondary cardiovascular prevention outcomes

Were similar for the secondary endpoint that was just mentioned and the rates of cardiovascular and all-cause mortality were similar in the ala glutenin placebo groups there are also similar rates of withdrawal due to adverse events in both treatment groups about ten percent and other adverse events of interest with this particular class of drugs we’re as follows

There were no differences between alec lipton and placebo in the incidence of hypoglycemia including severe hypoglycemia no difference in reported malignancies and there were no cases of pancreatic cancer there were no differences in renal function including the initiation of dialysis and there were low and similar frequencies of acute and chronic pancreatitis in

Each treatment group so our conclusion of the study is that in patients with type 2 diabetes in recent acute coronary syndrome major adverse cardiovascular events for the dpp-4 inhibitor alig lipton were not increased compared with placebo thank you thank you very much so do you kind of oppose your questions now for dr. white a dr. white i’m going to jump ahead to

The sabre trial and ask about the heart failure finding in that and what you think it means for the class of dpp-4 inhibitors well first of all i appreciate the question but i’m i would not think it’d be fair to the sabre speaker for me to jump ahead and ask questions about his trial so perhaps it’s better if he had answers that question he’s speaking right after

Me but i’m asking you about it for other dpp force well all i can tell you is that in this particular study in examine heart failure was not increased on alec lipton relative to placebo for hospitalization for heart failure however we have not completely finished our analysis of all the secondary cardiovascular endpoints because we just got locked the database

About five weeks ago so there are many other aspects of this trial that have are not in this today’s presentation larry euston cardio brief is there a compelling reason to take this drug well the way i look at it from my colleagues in diabetology is that you know right now the first line therapy worldwide is metformin what should be the second drug is sort of up in

The air people use so finally your reels they have some concerns you can use insulin you can use tz ds i think when you have data such as this supporting a lack of a safety signal in a very high-risk population it gives law in hants credibility to the use of a dpp-4 inhibitor as the second drug in addition to metformin which i by the way to admissions but two-thirds

Of our patients were on metformin in the trial it was balanced between the treatment group i think that would be compelling yes well it lowers the lowers glycemic index is significantly and as we know and treatment of type 2 diabetes as well as in type 1 diabetes if you are lowering a1c levels you’re lowering micro vascular event rate such as retinopathy nephropathy

So i think that there is that benefit now what does we don’t have benefit in these shorter term trials but you know we know from the prior literature that it might take five years plus before will terminate down the screen macrovascular benefit of lowering blood sugar’s over a sustained period of time and with a drug which doesn’t enhance cardiovascular risk for the questions

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Late Breaking Trials on Risk factors and Diabetes: William B WHITE (Farmington, US): By Cardioletter