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Diabetes Patients With High Triglycerides and Low HDL Cholesterol get the Most Benefit From Fenofibrate Treatment: New Data From the FIELD Study

Sydney (ots/PRNewswire)

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 (<1.03 mmol/L-40mg/dL
in men and <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 <1.8 mmol/L-70mg/dL with statin therapy, cardiovascular
risk is almost 50% higher for patients with high triglyceride (>2.3
mmol/L-200mg/dL) than those with lower triglyceride, and 40% higher
in those with low HDL cholesterol (< 0.96 mmol/L-37mg/dL) than in
those with higher HDL cholesterol.(2, 3)
Low plasma HDL cholesterol (<1.03 mmol/L-40mg/dL in men and <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 metabolic syndrome.
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 high
triglycerides.
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, added:
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 >40 inches in men and >35 inches in women) AND
  • Triglycerides greater than or equal to 150 mg/dL
  • HDL cholesterol <40 mg/dL in men and <50 mg/dL in women
  • Blood pressure greater than or equal to 130/85 mmHg (or on antihypertensive treatment)
  • 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 prevented.
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.
References
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 2005;366:1849-61.
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 2007;370:1687-97.
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.

Contact:

For further information contact: 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,
gfulcher@med.usyd.edu.au