SYDNEY, Australia, Feb. 26 /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.
