FIELD New results

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FIELD New results
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Aims of the FIELD eye study

• FIELD sub-analysis
• To analyse the reasons for reduction in laser
  therapy in FIELD
• Ophthalmology sub-study
• To assess the effect of fenofibrate on the
  progression of diabetic retinopathy in a
  sub-group of FIELD patients

FIELD Study Investigators. The Lancet. 2007
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First course of laser therapy

• Rapid benefits of fenofibrate were seen from
  eight months onward and increased throughout the
  study period
• These benefits were additive to tight blood
  pressure and glycaemic control

FIELD Study Investigators. The Lancet. 2007
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The risk reduction was essentially due to macular
oedema

• A significant 31 reduction due to macular oedema
  related laser treatment
• A significant 30 (p0.015) reduction for
  proliferative retinopathy

FIELD Study Investigators. The Lancet. 2007
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Multiple courses of laser therapy
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Fenofibrate benefits patients from cumulative use
of laser therapy

• The relative reduction seen with fenofibrate was
  significant in patients without prior retinopathy
  (49, p0.0002)

Fenofibrate
Favours fenofibrate
FIELD Study Investigators. The Lancet. 2007
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Summary

• Main study findings
• -31 first laser overall p0.0002
• -31 for maculopathy p0.002
• -30 for proliferative retinopathy p0.015
• -37 total laser therapies p0.0003
• -49 all laser - primary p0.0002

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FIELD Eye Sub-study
1012 patients entered the ophthalmology sub-study
512 assigned to fenofibrate 24 retinopathy
history 488 no retinopathy history
500 assigned to placebo 22 retinopathy
history 478 no retinopathy history
19 deaths 57 sub-study follow-up not available 3
withdrew consent
16 deaths 67 sub-study follow-up not available 0
withdrew consent
421 assessed at end of study
429 assessed at end of study
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Sub-study main endpoint

• Development of retinopathy defined as at least a
  2-step increase in the ETDRS grade after 2 or
  more years of follow-up for all patients. Also
  sub classified as
• Primary prevention 2-step progression to
  retinopathy in those with a baseline grade of 15
  or less.
• Secondary prevention 2-step progression of
  existing retinopathy in those with a baseline
  grade of 20 or greater

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Sub-study composite endpoint

• Exploratory combined outcome characterizing
  significant retinal pathology, composed of
• 2-step progression of retinopathy grade
• development of macular oedema
• or laser therapy

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2-step progression of retinopathy grade (ETDRS)
and macular oedema
79 reduction
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Exploratory composite endpoint

• laser therapy
• 2-step progression of retinopathy grade
• macular oedema

34 reduction
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Summary

• Sub-study findings
• -79 first laser therapy p0.0004
• -79 2-step progression, p0.004
• (existing retinopathy)
• -64 macular oedema p0.09
• -34 combined end-point p0.022
• (laser, macular oedema,
• 2-step progression)

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Clinical Application - 5 years treatment with
fenofibrate

• With pre-existing retinopathy
• Avoid first laser NNT 17
• 16 fewer multiple laser events per 100 Rx
• Without known prior eye disease
• Avoid first laser NNT 90
• 2.8 fewer multiple laser events per 100 Rx

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Conclusions

• In all subjects with diabetes, the use of
  fenofibrate could be considered for both its
  macro- and microvascular benefits
• Even for subjects on statin therapy at target
  LDL-C, fenofibrate could be considered as add-on
  therapy to further attenuate residual
  diabetes-mediated risk and its microvascular
  complications
• (ACCORD study will provide further evidence for
  combination statin-fenofibrate therapy)

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Other tertiary outcomes
Hospitalisations for angina pectoris1
Amputations2
RR 0.82 (95 CI 0.69-0.99)
RR 0.62 (95 CI 0.43-0.90)
p0.038
p0.011
300
100
-18
252
-38
73
5.1
75
208
200
1.5
4.3
45
50
Number of hospitalisations
Number of amputations
1.0
100
25
0
0
Placebo
Fenofibrate
Placebo
Fenofibrate

• FIELD study investigators. Atherosclerosis,
  Abstract We-S15 2 Atherosclerosis in Supplement
  2006 7(3) 342
• FIELD study investigators. Oral
  communication-AHA, 2007.

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Silent MI
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On-study myocardial infarction(9795 subjects
with T2DM)
Total MI 640 6.5 Clinical MI 395
4.0 Silent MI 245 2.5
245
395
9155
Silent MI 40 of all MIs
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Results
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Conclusions

• Silent MI is common in individuals with type 2
  diabetes - almost 40 of all MI
• There were 16 fewer first silent MI events on
  fenofibrate (p 0.154)
• Fenofibrate significantly reduced the occurrence
  all MI events by 20 (95 CI 6-31, p0.006)
• After silent MI, fenofibrate reduced the risk of
  further clinical CVD events (p0.008)

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Dyslipidaemia
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CVD Event Rate Reductions for Dyslipidemia (HDL-C
criteria for Metabolic Syndrome)
Placebo Fenofibrate HR (95
CI) HR P () ()
TG ? 2.3 mmol/L 17.2 13.4 Low
HDL-C 15.1 13.0 Triglyceride ? 2.3 mmol/L plus
low HDL-C 17.8 13.5 Mlt1.03 mmol/L Flt1.29
mmol/L
0.76 0.007 0.85 0.020 0.74 0.007
0.5 0.6 0.7 0.8 0.9 1.0
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CVD Event Rate Reductions for Dyslipidemia (HDL-C
criteria for Metabolic Syndrome)
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CVD Event Rate Reductions for Dyslipidemia (High
TG and/or low HDL-C as defined by NCEP-ATP III)
Placebo Fenofibrate HR (95 CI)
HR P () ()
Triglyceride criteria (? 2.3 mmol/L) 17.2 13.4 HD
L-C lt 1 mmol/L both genders 18.1 15.3 Triglyce
ride ? 2.3 mmol/L plus HDL-C lt 1
mmol/L 19.8 15.0
0.76 0.007 0.84 0.031 0.74 0.014
0.5 0.6 0.7 0.8 0.9 1.0
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CVD Event Rate Reductions for Dyslipidemia (High
TG and/or low HDL-C as defined by NCEP-ATP III)
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LIPANTHYL

• Lipanthyl sníil výskyt kardiovaskulárních príhod
  o 26 u pacientu s dyslipidémii typickou
  pro DM typu 2

• Práve pacienti s diabetem mellitem 2. typu nebo
  metabolickým syndromem profi tují nejvíce z lécby
  Lipanthylem

A.. Keech Features of Metabolic Syndrome
Identify Individuals with Type 2 Diabetes
Mellitus at high risk for CV events and greater
benefits of fenofibrate. AHA 2007, Orlando,
Abstract
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Mikrovaskulární efekty a úloha fenofibrátu
LIPANTHYL
31
p0.0002
Retinopatie
Albuminurie
14
p0,002
38
p0,001
Amputace
0
5
10
15
20
25
30
35
Redukce rizika ()
Lipanthyl je jediné hypolipidemikum s
prokázanou úcinnost na makro a zároven
mikrovaskulární komplikace DM
Lancet 2007, AHA 2007 abstract