Fenofibrate Intervention and Event Lowering in Diabetes FIELDFIELD Presented at The American Heart...

Fenofibrate Intervention and Event Lowering in Fenofibrate Intervention and Event Lowering in DiabetesDiabetes

Fenofibrate Intervention and Event Lowering in Fenofibrate Intervention and Event Lowering in DiabetesDiabetes

FIELDFIELDFIELDFIELD

Presented atPresented atThe American Heart Association Scientific The American Heart Association Scientific

Sessions, November 2005 Sessions, November 2005

Presented by Dr. Anthony KeechPresented by Dr. Anthony Keech

www. Clinical trial results.org

FIELD: BackgroundFIELD: BackgroundFIELD: BackgroundFIELD: Background

•Statins, whose main action is to lower LDL, have Statins, whose main action is to lower LDL, have been shown to have significant beneficial effects in been shown to have significant beneficial effects in diabeticsdiabetics

•Fibrates affect different components of the lipid Fibrates affect different components of the lipid profile by preferentially increasing HDL, lowering profile by preferentially increasing HDL, lowering triglycerides, and increasing the size of LDL particles triglycerides, and increasing the size of LDL particles

•Fibrates could be beneficial for diabetics in whom Fibrates could be beneficial for diabetics in whom low HDL, high triglycerides, and small LDL particles low HDL, high triglycerides, and small LDL particles are more common than in the general populationare more common than in the general population

•The goal of the study is to evaluate treatment with The goal of the study is to evaluate treatment with fenofibrate compared with placebo in patients with fenofibrate compared with placebo in patients with diabetes who are at risk for coronary heart diseasediabetes who are at risk for coronary heart disease

●

AHA 2005AHA 2005


Fenofibrate(200 mg daily)

n=4895

Fenofibrate(200 mg daily)

n=4895

Endpoints: Primary – Composite of CHD death or non-fatal MI at 5 year follow-up Secondary – Composite of total CV events, CV mortality, total mortality, stroke,

coronary revascularization and all revascularization at 5 year follow-up

Endpoints: Primary – Composite of CHD death or non-fatal MI at 5 year follow-up Secondary – Composite of total CV events, CV mortality, total mortality, stroke,

coronary revascularization and all revascularization at 5 year follow-up

FIELD: DesignFIELD: DesignFIELD: DesignFIELD: Design

ESC 2005ESC 2005

PlaceboN=4900

PlaceboN=4900

9795 patients, Age 50-75 years, type 2 diabetes diagnosed after age 35 years, no clear indication for cholesterol-lowering therapy at

baseline (total cholesterol 116-251 mg/dL, plus either total cholesterol to HDL ratio ≥4.0 or triglyceride >88.6 mg/dL

9795 patients, Age 50-75 years, type 2 diabetes diagnosed after age 35 years, no clear indication for cholesterol-lowering therapy at

baseline (total cholesterol 116-251 mg/dL, plus either total cholesterol to HDL ratio ≥4.0 or triglyceride >88.6 mg/dL


FIELD: Primary EndpointFIELD: Primary EndpointFIELD: Primary EndpointFIELD: Primary Endpoint

5.2%

5.9%

0%

2%

4%

6%

Fenofibrate Placebo

5.2%

5.9%

0%

2%

4%

6%

Fenofibrate Placebo

• The primary The primary composite endpoint of composite endpoint of CHD death or non-fatal CHD death or non-fatal MI was not significantly MI was not significantly lower in the fenofibrate lower in the fenofibrate group compared to the group compared to the placebo group. placebo group.

Composite CHD death or nonfatal MI at 5 YearsComposite CHD death or nonfatal MI at 5 Years(% of treatment arm)(% of treatment arm)

AHA 2005AHA 2005

p=0.16


FIELD: Primary EndpointFIELD: Primary EndpointFIELD: Primary EndpointFIELD: Primary Endpoint

2.2%

3.2%

1.9%

4.2%

0%

2%

4%

CHD Death Non-fatal MIFenofibrate Placebo

2.2%

3.2%

1.9%

4.2%

0%

2%

4%

CHD Death Non-fatal MIFenofibrate Placebo

•CHD death was not CHD death was not significantly different significantly different between treatment between treatment groupsgroups•Nonfatal MI was Nonfatal MI was significantly lower in the significantly lower in the fenofibrate group fenofibrate group compared with the compared with the placebo group.placebo group.

CHD death or nonfatal MI at 5 year follow-up CHD death or nonfatal MI at 5 year follow-up (% of treatment arm)(% of treatment arm)

P=0.22

P=0.01

AHA 2005AHA 2005


FIELD: Secondary Endpoint FIELD: Secondary Endpoint FIELD: Secondary Endpoint FIELD: Secondary Endpoint

12.5%

13.9%

0%

5%

10%

15%

Fenofibrate Placebo

12.5%

13.9%

0%

5%

10%

15%

Fenofibrate Placebo

• The secondary The secondary composite composite endpoint of total endpoint of total CV events was CV events was significantly lower significantly lower in the fenofibrate in the fenofibrate group compared group compared to the placebo to the placebo group (% of group (% of treatment arm)treatment arm)

Secondary Composite Endpoint of Total CV Secondary Composite Endpoint of Total CV events at 5 year Follow-upevents at 5 year Follow-up

p=0.035

AHA 2005AHA 2005



2.9%

7.3%

3.2%

2.6%

6.6%

3.6%

0%

2%

4%

6%

8%

CV Mortality Total Mortality Stroke

Fenofibrate Placebo

2.9%

7.3%

3.2%

2.6%

6.6%

3.6%

0%

2%

4%

6%

8%

CV Mortality Total Mortality Stroke

Fenofibrate Placebo

• CV Mortality, Total CV Mortality, Total Mortality, and Stroke Mortality, and Stroke were not significantly were not significantly different between the different between the fenofibrate and fenofibrate and placebo groupsplacebo groups

Individual Components of Secondary EndpointIndividual Components of Secondary Endpoint

p=0.41

p=0.18

p=0.36

AHA 2005AHA 2005



5.9%

7.4%

9.6%

7.8%

0%

5%

10%

Coronary revascularization All Revascularization

Fenofibrate Placebo

5.9%

7.4%

9.6%

7.8%

0%

5%

10%

Coronary revascularization All Revascularization

Fenofibrate Placebo

• Percentage of Percentage of coronary coronary revascularization and revascularization and all revascularization all revascularization were significantly were significantly lower in the lower in the fenofibrate group fenofibrate group compared to placebocompared to placebo

Individual Components of Secondary Endpoint

P=0.003

P=0.001

AHA 2005AHA 2005


FIELD: LimitationsFIELD: LimitationsFIELD: LimitationsFIELD: Limitations

•The results of this study may have been confounded by uneven use of The results of this study may have been confounded by uneven use of statins between the two groups as 17% of the placebo group was statins between the two groups as 17% of the placebo group was prescribed a statin during the trial compared with 7% in the fenofibrate prescribed a statin during the trial compared with 7% in the fenofibrate groupgroup

•Although adjusting for statin use yields a statistically significant Although adjusting for statin use yields a statistically significant reduction in the primary endpoint (19%, p=0.01) this may slightly reduction in the primary endpoint (19%, p=0.01) this may slightly overestimate the effect for the fenofibrate group since the use of statins overestimate the effect for the fenofibrate group since the use of statins was not randomizedwas not randomized

•In terms of adverse effects, the fenofibrate group showed small In terms of adverse effects, the fenofibrate group showed small increases in pancreatitis (0.5% vs 0.8%, p=0.031) and pulmonary increases in pancreatitis (0.5% vs 0.8%, p=0.031) and pulmonary embolism (0.7% vs 1.1%, p=0.022)embolism (0.7% vs 1.1%, p=0.022)

•Although fenofibrate reduced triglycerides and LDL, there was virtually Although fenofibrate reduced triglycerides and LDL, there was virtually no increase shown in HDLno increase shown in HDL

AHA 2005AHA 2005


FIELD: SummaryFIELD: SummaryFIELD: SummaryFIELD: Summary

• Among patients with diabetes at risk of coronary heart disease, there was no Among patients with diabetes at risk of coronary heart disease, there was no statistically significant difference in the primary composite endpoint of CHD statistically significant difference in the primary composite endpoint of CHD death or nonfatal MI. There was, however, a significant reduction in nonfatal death or nonfatal MI. There was, however, a significant reduction in nonfatal MI in the fenofibrate group compared with placebo.MI in the fenofibrate group compared with placebo.

• The secondary composite endpoint of total cardiovascular events was The secondary composite endpoint of total cardiovascular events was significantly lower in the fenofibrate group primarily due to reductions in significantly lower in the fenofibrate group primarily due to reductions in nonfatal MI and revascularizations.nonfatal MI and revascularizations.

•The results may have been confounded by a difference in statin use between The results may have been confounded by a difference in statin use between the two groups as 17% of the placebo group were prescribed statins during the two groups as 17% of the placebo group were prescribed statins during the trial compared to 7% in the fenofibrate group. This may have attenuated the trial compared to 7% in the fenofibrate group. This may have attenuated treatment effect differences.treatment effect differences.

•The ACCORD trial, which will randomize diabetics to either fenofibrate or The ACCORD trial, which will randomize diabetics to either fenofibrate or placebo with all patients taking simvastatin, will provide a more definitive placebo with all patients taking simvastatin, will provide a more definitive answer regarding the benefit of fenofibrates in diabetics.answer regarding the benefit of fenofibrates in diabetics.

• Among patients with diabetes at risk of coronary heart disease, there was no Among patients with diabetes at risk of coronary heart disease, there was no statistically significant difference in the primary composite endpoint of CHD statistically significant difference in the primary composite endpoint of CHD death or nonfatal MI. There was, however, a significant reduction in nonfatal death or nonfatal MI. There was, however, a significant reduction in nonfatal MI in the fenofibrate group compared with placebo.MI in the fenofibrate group compared with placebo.

• The secondary composite endpoint of total cardiovascular events was The secondary composite endpoint of total cardiovascular events was significantly lower in the fenofibrate group primarily due to reductions in significantly lower in the fenofibrate group primarily due to reductions in nonfatal MI and revascularizations.nonfatal MI and revascularizations.

•The results may have been confounded by a difference in statin use between The results may have been confounded by a difference in statin use between the two groups as 17% of the placebo group were prescribed statins during the two groups as 17% of the placebo group were prescribed statins during the trial compared to 7% in the fenofibrate group. This may have attenuated the trial compared to 7% in the fenofibrate group. This may have attenuated treatment effect differences.treatment effect differences.

•The ACCORD trial, which will randomize diabetics to either fenofibrate or The ACCORD trial, which will randomize diabetics to either fenofibrate or placebo with all patients taking simvastatin, will provide a more definitive placebo with all patients taking simvastatin, will provide a more definitive answer regarding the benefit of fenofibrates in diabetics.answer regarding the benefit of fenofibrates in diabetics.

AHA 2005AHA 2005

Fenofibrate Intervention and Event Lowering in Diabetes FIELDFIELD Presented at The American Heart...

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