Fenofibrate Intervention and Event Lowering in Diabetes

1
Fenofibrate Intervention and Event Lowering in
Diabetes
A randomised trial of the effects of fenofibrate
on coronary morbidity and mortality in people
with diabetes

• The FIELD Study Investigators

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Contributors

• Management Committee
• A Keech (study chairman), P Barter, J Best, R
  Scott, RJ Simes, M-R Taskinen (Executive
  Committee) P Colman, M dEmden, T Davis, P
  Drury, C Ehnholm, P Glasziou, D Hunt, YA
  Kesäniemi, M Laakso, D Sullivan, M Whiting
• J-C Ansquer, B Fraitag (non-voting sponsor
  attendees)
• P Forder, A Pillai (study statisticians)
• Outcomes Assessment Committee
• D Hunt (chairman), N Anderson, G Hankey, S
  Lehto, S Mann, M Romo
• LP Li (outcomes officer, in attendance)
• Safety and Data Monitoring Committee
• S MacMahon (chairman), C Hennekens, S Pocock, A
  Tonkin, L Wilhelmsen
• Coordinating centres and laboratory staff
• 300 medical and nurse investigators and 10 000
  patients

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Objective
To provide the first randomised evidence of the
effects of fenofibrate on the risk of major
coronary disease events (nonfatal myocardial
infarction or CHD death) in patients with
diabetes

• with and without pre-existing vascular disease
• men and women
• younger (lt65 years) and older (65 years)
• with and without other lipid abnormalities

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Outcomes

• Primary outcome
• First occurrence of nonfatal MI or CHD death

• Secondary outcomes
• Total CVD events
• (MI, stroke, CVD death, coronary and carotid
  revascularisation)
• Coronary peripheral revascularisation

• Stroke
• CHD deaths
• CVD deaths
• Total mortality
• Primary outcome for subgroup analyses

• Tertiary outcomes
• Progression of renal disease
• Laser treatment for diabetic retinopathy
• Nonfatal cancers

• Vascular neuropathic amputations
• Hospitalisation for angina pectoris
• Hospital admissions

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Flow of patients
9795 randomised 6051 Australia, 2351 New Zealand,
1393 Finland
4900 Placebo
4895 Fenofibrate 200 mg
4 withdrew consent 12 lost to follow-up
5 withdrew consent 10 lost to follow-up
4852 (99) primary outcome confirmed
4856 (99) primary outcome confirmed
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Results primary outcome
CHD events (CHD death nonfatal MI)
HR 0.89 95 CI 0.751.05 P0.16
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Total CVD events
HR 0.89 95 CI 0.800.99 P0.035 NNT 70
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Coronary revascularisations
HR 0.79 95 CI 0.680.93 P0.003
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Results secondary outcomes
Placebo Fenofibrate HR (95 CI) P
() ()
0.035 0.41 0.18 0.36 0.43 0.003 0.001
Total CVD events 13.9 12.5 CVD
mortality 2.6 2.9 Total mortality 6.6 7.3 Total
stroke 3.6 3.2 Nonhaemorrhagic
stroke 3.2 2.9 Coronary revascularisation 7.4
5.9 All revascularisation 9.6 7.8
favours fenofibrate favours placebo
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Total CVD in subgroups
Prior CVD HR 1.02 95 CI 0.861.20 P0.85
No prior CVD HR 0.81 95 CI 0.700.94 P0.004
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Results retinal laser therapy
HR 0.70 95 CI 0.580.85 P0.0003
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Safety non-CVD causes of death
Placebo Fenofibrate n () n ()

• Cancer 148 (3.0) 168 (3.4)
• Respiratory disease 16 (0.3) 19 (0.4)
• Trauma 12 (0.2) 11 (0.2)
• Other 20 (0.4) 18 (0.3)
• Any death 196 (4.0) 216 (4.4)

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Conclusions

• Observed effects of fenofibrate appear to have
  been modestly attenuated by differential statin
  use.
• Use of fenofibrate should now be considered in
  the context of well-established statin therapy
• its main use is likely to be in combination
• fenofibrate was well tolerated alone and in
  combination with statins.

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Conclusions

• The effect of fenofibrate on the primary outcome
  (CHD death or nonfatal MI) was not statistically
  significant.
• However, fenofibrate significantly reduced total
  CVD events, particularly due to reductions in
  nonfatal MI and coronary revascularisation,
  without reducing fatal events.
• Fenofibrate also conferred beneficial
  microvascular-associated effects on renal and eye
  disease.