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8/3/2019 Presentation Nit In

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Background of accord

Need for trial

Accord study was a maximum effort todetermine whether treating three major riskfacors as possible

(hypergycemia, hypertension andtrigyceride:high density lipoprotien

ratio)would decrease the 5 yr incidence ofcardiovascular death, nonfatal infarction,andnonfatal stroke.


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Design


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Primary and secondary outcome


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Accord 5 yr incidence outcome


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Large complex research program Multi-center, randomized, controlled factorial trials of 3 approaches to

reduce CVD in T2DM

Glycemia Trial Open Label with Blinded Endpoint Assessment

Interventions designed to produce 1-1.5% difference in A1C

Goals: A1C < 6% vs 7 7.9% Primary endpoint: major CVD events

Participants: diverse group of middle-aged and older adults withestablished T2DM with or at high risk for CVD

High use of evidence-based background therapies: ASA, ACE-I, BB,

Statins Results should be interpreted in context of population studied and

other therapies received.

ACCORD Trial Design Summary


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10251 patients

Median diabetes duration-10 yr

Mean age-62 yr One third had a previous cardiovascular

disease,remaining 2/3 have at least two major

cvd risk factors


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Intensive glycemia and combination offenofibrate and simvastatin reduced theproportion whose retinopathy progressed

by about one-third Effects were consistent across subgroups

No statistically significant effect ofintensive blood pressure

No subgroup with effect

ACCORD Eye Study Conclusions


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Intensive treatment of glycemia in the ACCORDcohort did not reduce the risk of compositemeasures of advanced microvascular outcomes

Intensive therapy delayed the onset ofalbuminuria and some measures of eyecomplications and neuropathy

Microvascular benefits of intensive therapyshould be weighed against increase in total andCVD-related mortality, increased weight gain,and high risk for severe hypoglycemia

Conclusions


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Conclusion (1)

ACCORD Lipid does not support use of the combination of

fenofibrate and simvastatin, compared to simvastatin alone,

to reduce CVD events in the majority of patients with T2DM

who are at high risk for CVD


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Conclusion (2)

Subgroup analyses suggesting heterogeneity in response to

combination therapy by gender or by the presence of

significant dyslipidemia require further investigation


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The ACCORD BP trial evaluated the effect of

targeting a SBP goal of120 mm Hg, compared to a

goal of140

mm Hg, in patients with type 2 diabetesat increased cardiovascular risk.

The results provide no conclusive evidence that the

intensive BP control strategy reduces the rate of a

composite of major CVD events in such patients.

Conclusions


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Achieved SBPs and delta SBP between randomizedgroups supported continuation of the ACCORD BP trialinto the full-scale trial.

With this treatment algorithm SBP was lowered to an

average of120 mm Hg in patients with type 2 DMover 16 months, using an average of about 3medications.

The data suggest ACCORD will provide definitiveclinical trial data on possible benefits and risks oftreating to lower BP goals in patients with type 2 DM.

Vanguard BP Conclusions


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In people with type 2 diabetes at high risk for CVD, with anA1C of 7.5% or more, a therapeutic strategy that targetsan A1C


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ACCORD Conclusions

Compared to a strategy targeting A1C levels of 7-7.9%, atherapeutic strategy using currently available therapies totarget near-normal A1C levels in people with longstandingT2DM and either CVD or additional CVD risk factors overaverage 3.5 years:

Increased mortality

Did not reduce a composite of major CVD events(primary outcome)

Mortality results consistent across several subgroups

Suggestion of reduced major CVD events in 2subgroups: primary prevention and A1C


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ACCORD Conclusions, cont. ACCORD identified a previously unknown harm of a strategy

of intensive glucose lowering in high-risk individuals with

T2DM

ACCORD designed to test a therapeutic strategy, not any

specific component(s) of the strategy; numerous factors

differed between the randomized groups Potential causes are difficult, if not impossible, to separate out

from other factors that differ by group

Example: An ACCORD participant may or may not be on a drug

for various reasons, so we cant separate out effects of the

drug from effects of patient characteristics (some of whichwere not measured)

Exploratory analyses examined various medications and

hypoglycemia no specific cause of higher mortality found


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