FIELD New results
Aims of the FIELD eye study
A. “FIELD sub-analysis”;
To analyse the reasons for reduction in laser
therapy in FIELD
B. “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
First course of laser therapy
-31%
•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
The risk reduction was essentially due to
macular oedema
 A significant 31% reduction due to macular oedema related
laser treatment
 A significant 30% (p=0.015) reduction for proliferative
retinopathy
FIELD Study Investigators. The Lancet. 2007
Multiple courses of laser therapy
Event
1 laser only
Placebo
Fenofibrate
121
85
95% CI
P-value
0.63, 0.49-0.81, 0.0003
2-12 laser
courses
Hazard
Ratio
37% reduction
117
70
Fenofibrate benefits patients from
cumulative use of laser therapy
 The relative reduction seen with fenofibrate was
significant in patients without prior retinopathy
(49%, p=0.0002)
Fenofibrate
Favours
fenofibrate
FIELD Study Investigators. The Lancet. 2007
Summary
Main study findings:
 -31%
first laser overall
p=0.0002
 -31%
for maculopathy
p=0.002
 -30%
for proliferative retinopathy
p=0.015
 -37%
total laser therapies
p=0.0003
 -49%
all laser - primary
p=0.0002
FIELD Eye Sub-study
1012 patients entered the
ophthalmology sub-study
500 assigned to placebo
22 retinopathy history
478 no retinopathy
history
512 assigned to
fenofibrate
24 retinopathy history
488 no retinopathy history
19 deaths
16 deaths
57 sub-study followup not available
67 sub-study followup not available
3 withdrew consent
0 withdrew consent
421 assessed at end of study
429 assessed at end of study
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
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
2-step progression of retinopathy
grade (ETDRS) and macular oedema
Group
Placebo
Fenofibrate
p value
57
46
0.19
(12.3%)
(9.6%)
43
43
(11.7%)
(11.4%)
14
3
(14.6%)
(3.1%)
10
4
(2.2%)
(0.8%)
All patients
No prior
retinopathy
Prior
retinopathy*
Macular
oedema
*79% reduction
0.87
0.004
0.09
Exploratory composite endpoint:
 laser therapy
 2-step progression of retinopathy grade
 macular oedema
Event
Composite
Endpoint*
Placebo Fenofibrate
75
*34% reduction
53
Hazard
Ratio
95% CI
p-value
0.66
0.47-0.94
0.022
Summary
Sub-study findings:
 -79% first laser therapy
p=0.0004
 -79% 2-step progression,
p=0.004
(existing retinopathy)
 -64% macular oedema
p=0.09
 -34% combined end-point
p=0.022
(laser, macular oedema,
2-step progression)
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
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 addon therapy to further attenuate residual
diabetes-mediated risk and its microvascular
complications
(ACCORD study will provide further evidence for
combination statin-fenofibrate therapy)
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)
p=0.038
p=0.011
Number of hospitalisations
252
200
5.1%
100
-18%
208
4.3%
100
0
Number of amputations
300
75
73
1.5%
50
-38%
45
1.0%
25
0
Placebo
Fenofibrate
Placebo
Fenofibrate
1. FIELD study investigators. Atherosclerosis, Abstract We-S15: 2 Atherosclerosis in Supplement 2006; 7(3): 342
2. FIELD study investigators. Oral communication-AHA, 2007.
Silent MI
On-study myocardial infarction
(9795 subjects with T2DM)
None
Silent
Clinical
Total MI = 640 = 6.5%
245
395
Clinical MI = 395 = 4.0%
Silent MI = 245 = 2.5%
9155
Silent MI = 40% of all MIs
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 631%, p=0.006)
After silent MI, fenofibrate reduced the risk
of further clinical CVD events (p=0.008)
Dyslipidaemia
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
0.76
Low HDL-C*
15.1
13.0
0.85
0.020
13.5
0.74
0.007
0.007
Triglyceride  2.3 mmol/L
plus low HDL-C
17.8
*M<1.03 mmol/L; F<1.29 mmol/L
0.5
0.6 0.7 0.8
0.9
1.0
CVD Event Rate Reductions for Dyslipidemia
(HDL-C criteria for Metabolic Syndrome)
Dyslipidaemic criteria
Hazard Ratio
(NNT)
Event rate
Event Rate
Placebo
Placebo
Triglyceride criteria
( 2.3 mmol/L)
0.76 (26.3)
(17.2)
(13.4)
Low HDL-C*
0.85 (47.6)
(15.1)
(13.0)
TG  2.3 mmol/L plus
low HDL-C
0.74 (23.3)
(17.8)
(13.5)
*M<1.03 mmol/L; F<1.29 mmol/L
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
0.76
18.1
15.3
0.84
0.031
15.0
0.74
0.014
0.007
HDL-C < 1 mmol/L
both genders
Triglyceride  2.3 mmol/L
plus HDL-C < 1 mmol/L
19.8
0.5
0.6 0.7 0.8
0.9
1.0
CVD Event Rate Reductions for Dyslipidemia
(High TG and/or low HDL-C as defined by NCEP-ATP III)
Dyslipidaemic criteria
Hazard Ratio
(NNT)
Event rate
Event Rate
Placebo
Placebo
Triglyceride criteria
( 2.3 mmol/L)
0.76 (26.3)
(17.2)
(13.4)
HDL-C < 1 mmol/L
both genders
0.84 (37.0)
(18.1)
(15.3)
Triglyceride  2.3
mmol/L plus
HDLc < 1 mmol/L
0.74 (20.8)
(19.8)
(15.0)
LIPANTHYL


Lipanthyl snížil výskyt kardiovaskulárních příhod o 26 % u pacientů
s dyslipidémii typickou pro DM typu 2
Právě pacienti s diabetem mellitem 2. typu nebo metabolickým syndromem profi
tují nejvíce z léčby 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
LIPANTHYL
Mikrovaskulární efekty a úloha fenofibrátu
p=0.0002 31%
Retinopatie
Albuminurie
p=0,002
14%
p=0,001
Amputace
0
5
10
15
20
25
30
38%
35
Redukce rizika (%)
Lipanthyl je jediné hypolipidemikum s prokázanou
účinnost na makro a zároveň mikrovaskulární
komplikace DM
Lancet 2007, AHA 2007 abstract