SYDNEY, Feb. 26 /CNW/ - Fenofibrate treatment reduces cardiovascular
disease (CVD) risk (defined by total cardiovascular events: the composite of
cardiovascular death, myocardial infarction, stroke, and coronary and carotid
revascularization) in patients with type 2 diabetes and atherogenic
dyslipidemia, that is, the combination of high triglyceride (2.3
mmol/L-200mg/dL or higher) and low high-density lipoprotein (HDL) cholesterol
(less than 1.03 mmol/L-40mg/dL in men and less than 1.3 mmol/L-50mg/dL in
women), according to new data from the Fenofibrate Intervention and Event
Lowering in Diabetes (FIELD) study published in Diabetes Care.
In these patients, fenofibrate treatment was associated with a
significant 27% relative reduction in the risk of cardiovascular events,
compared with 11% in FIELD patients overall(1).
Professor Russell Scott, investigator and executive member of the FIELD
Study Management Committee, Director of the Lipid and Diabetes Research Group,
and Professor of Medicine, Christchurch Hospital, New Zealand, said:
This 27% relative reduction in total CVD events with fenofibrate in type
2 diabetes patients with marked atherogenic dyslipidemia is of a similar order
to that observed with statin treatment. Physicians can prevent one fatal or
non-fatal cardiovascular event by treating only 23 of these patients over 5
years with fenofibrate.
Patients with, or at increased risk of, type 2 diabetes often have an
abnormal combination of high triglycerides and low HDL cholesterol. Population
studies have shown that this predicts cardiovascular risk, partly independent
of levels of low-density lipoprotein (LDL) cholesterol.
In people with diabetes, even when the LDL cholesterol level is reduced
to less than 1.8 mmol/L-70mg/dL with statin therapy, cardiovascular risk is
almost 50% higher for patients with high triglyceride (greater than 2.3
mmol/L-200mg/dL) than those with lower triglyceride, and 40% higher in those
with low HDL cholesterol (less than 0.96 mmol/L-37mg/dL) than in those with
higher HDL cholesterol(2),(3).
Low plasma HDL cholesterol (less than 1.03 mmol/L-40mg/dL in men and less
than 1.3 mmol/L-50mg/dL in women) and elevated triglyceride (greater than or
equal to 1.7 mmol/L-150mg/dL) are key criteria of the metabolic syndrome
according to the old definition of the US National Cholesterol Education
Program Adult Treatment Panel III (NCEP ATPIII) guidelines(4).
In the FIELD study over 80% of patients met the NCEP ATPIII criteria for
This latest study from FIELD investigated whether cardiovascular risk and
the effects of fenofibrate treatment differed in type 2 diabetes patients with
and without the metabolic syndrome. It also examined the effect of more marked
atherogenic dyslipidaemia - the combination of low HDL cholesterol and higher
triglycerides (greater than or equal to 2.3 mmol/L-200mg/dL). One in five
FIELD patients had marked atherogenic dyslipidaemia and one in four marked
Patients with marked atherogenic dyslipidaemia had the greatest 5-year
risk of cardiovascular disease (17.8% in the placebo group). These patients
also derived the greatest clinical benefit from fenofibrate treatment, with a
27% reduction in CVD risk (from 17.8% to 13.5%, P=0.005). This risk was almost
two-fold (29.8%) in those patients who already had cardiovascular disease.
Placing the new findings in clinical context, Professor Scott said:
Atherogenic dyslipidemia, characterised by high triglycerides of at least
2.3 mmol/L-200mg/dL and low HDL-C, as defined by ATP III, is a strong
contributor to residual vascular risk in millions of patients with diabetes
treated with the best standard of care, including statin therapy. These new
findings, together with the microvascular benefits associated with
fenofibrate, argue for consideration of fenofibrate in the clinical management
of patients with type 2 diabetes and marked atherogenic dyslipidemia.
Professor Richard O'Brien, a diabetes specialist and Clinical Dean of
Medicine at the University of Melbourne, Austin and Northern Clinical Schools,
These findings on macrovascular disease build on earlier results of the
FIELD trial showing clear benefits for patients with microvascular
complications. Fenofibrate reduces the need for laser treatment in patients
with diabetic disease in the small vessels of the eyes. It also reduces the
risk of amputations resulting from disease in the small vessels of the limbs.
FIELD(5), a large international multicentre trial in which 9795 patients
were followed up over 5 years, was coordinated at the NHMRC Clinical Trials
Centre at the University of Sydney. Professor Anthony Keech, Professor of
Medicine, Cardiology and Epidemiology and Deputy Director of the trials
centre, is chair of the trial.
Notes for Editors
What is the FIELD study?
The FIELD trial was a randomised, double-blind, placebo-controlled study
in 9795 patients with type 2 diabetes. The study evaluated whether treatment
with fenofibrate (200 mg/day) for a median of 5 years could reduce
macrovascular and microvascular complications of type 2 diabetes.
Macrovascular study endpoints were major coronary events (primary) and total
cardiovascular events (secondary). Microvascular endpoints were laser
treatment for diabetic retinopathy, progression of albuminuria and
non-traumatic lower-extremity amputation.
What were the key macrovascular findings in the FIELD study?
After a mean of 5 years treatment, fenofibrate was associated with a
non-significant 11% reduction in the primary endpoint. However, there was a
significant reduction in the secondary endpoint (reduction by 11%, P=0.035).
This was mainly driven by 24% reduction in nonfatal MI (P=0.01) and 21%
reduction in coronary revascularisation (P=0.003)(5).
There was also evidence of benefit with fenofibrate for microvascular
endpoints, in particular reduction in first laser treatment for retinopathy
(by 31%, P=0.0002)(6),(7).
What is the metabolic syndrome?
The metabolic syndrome is characterised by a clustering of cardiovascular
risk factors which increase the risk of type 2 diabetes and cardiovascular
disease. Although the definition of metabolic syndrome varies among different
guidelines, one of the most widely accepted is that of the NCEP ATPIII(4)
which defines metabolic syndrome by the following criteria:
- Abdominal obesity (waist circumference greater than 40 inches in men
and greater than 35 inches in women) AND
- Triglycerides greater than or equal to 150 mg/dL
- HDL cholesterol less than 40 mg/dL in men and less than 50 mg/dL in
- Blood pressure greater than or equal to 130/85 mmHg (or on
- Elevated fasting plasma glucose (greater than or equal to 100 mg/dL).
What is meant by number needed to treat?
The NNT value provides a clinical context to the absolute reduction in
risk. This value is defined by the inverse of the absolute reduction in risk.
In this analysis, the NNT for fenofibrate in patients with marked atherogenic
dyslipidaemia was 23 patients needing to be treated for one event to be
By comparison, the Cholesterol Treatment Trialists' (CTT) Collaborators
(8) reported an absolute reduction in 5-year risk of major vascular events in
diabetes patients treated with statin therapy of 3.6%, i.e. NNT = 28.
1. Russell Scott, Richard O'Brien, Greg Fulcher, Chris Pardy, Michael
d'Emden, Dana Tse, Maria-Riitta Taskinen, Christian Ehnholm, Anthony
Keech, on behalf of the Fenofibrate Intervention and Event Lowering
in Diabetes (FIELD) Study Investigators. Effects of Fenofibrate
Treatment on Cardiovascular Disease Risk in 9,795 Individuals With
Type 2 Diabetes and Various Components of the Metabolic Syndrome: The
Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
Study. Diabetes Care 32:493-498
2. Miller M, Cannon CP, Murphy SA et al, PROVE-IT TIMI 22 Investigators.
Impact of triglyceride levels beyond low-density lipoprotein
cholesterol after acute coronary syndrome in the PROVE-IT TIMI 22
trial. J Am Coll Cardiol 2008; 51: 724-30.
3. Barter PJ, Gotto AM, LaRosa JC et al, Treating to New Targets
Investigators. HDL cholesterol, very low levels of LDL cholesterol,
and cardiovascular events. N Engl J Med 2007; 357: 1301-10.
4. National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III). Third Report of the National
Cholesterol Education Program (NCEP) Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult
Treatment Panel III). Final report. Circulation 2002;106: 3143-21.
5. Keech A, Simes RJ, Barter P et al. Effects of long-term fenofibrate
therapy on cardiovascular events in 9795 people with type 2 diabetes
mellitus (the FIELD study): randomised controlled trial. Lancet
6. Keech AC, Mitchell P, Summanen PA, et al, FIELD study investigators.
Effect of fenofibrate on the need for laser treatment for diabetic
retinopathy (FIELD study): a randomised controlled trial. Lancet
7. Colman P, Rajamani K, Li L-P et al. Benefits of long-term fenofibrate
therapy on amputations in type 2 diabetes mellitus in the FIELD
trial. Presented at the European Association for the study of
Diabetes (EASD), Rome, September 2008.
8. Efficacy of cholesterol-lowering therapy in 18 686 people with
diabetes in 14 randomised trials of statins: a meta-analysis
Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM,
Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent
C. Lancet. 2008 Jan 12;371(9607):117-25.
For further information:
For further information: New Zealand: Professor Russell Scott, Lipid &
Diabetes Research Group, Christchurch Hospital, Christchurch, +64-(3)-364-0449
or 0640, +64-(274)-366-380; Australia: Associate Professor Richard O'Brien,
Clinical School, Austin Hospital, Heidelberg, +61-(3)-9496-5585,
+61-(0)415-550-183; Professor Greg Fulcher, Northern Clinical School, Royal
North Shore Hospital, +61-(0)2-9926-8388, +61-(0)438-878-962,